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  • 51.
    Dahlén, Amelia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94158 USA.;Univ Calif San Francisco, Program Biol Sci, San Francisco, CA 94158 USA.;Univ Calif San Francisco, Program Human Genet, San Francisco, CA 94158 USA..
    Zarei, Mahdi
    Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94158 USA.;Univ Calif San Francisco, Program Biol Sci, San Francisco, CA 94158 USA.;Univ Calif San Francisco, Program Human Genet, San Francisco, CA 94158 USA..
    Melgoza, Adam
    Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94158 USA.;Univ Calif San Francisco, Program Biol Sci, San Francisco, CA 94158 USA.;Univ Calif San Francisco, Program Human Genet, San Francisco, CA 94158 USA..
    Wagle, Mahendra
    Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94158 USA.;Univ Calif San Francisco, Program Biol Sci, San Francisco, CA 94158 USA.;Univ Calif San Francisco, Program Human Genet, San Francisco, CA 94158 USA..
    Guo, Su
    Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94158 USA.;Univ Calif San Francisco, Program Biol Sci, San Francisco, CA 94158 USA.;Univ Calif San Francisco, Program Human Genet, San Francisco, CA 94158 USA..
    THC-induced behavioral stereotypy in zebrafish as a model of psychosis-like behavior2021In: Scientific Reports, E-ISSN 2045-2322, Vol. 11, no 1, article id 15693Article in journal (Refereed)
    Abstract [en]

    High doses of the Cannabis constituent Delta 9-tetrahydrocannabinol (THC) increase the risk of psychosis in humans. Highly accessible animal models are needed to address underlying mechanisms. Using zebrafish with a conserved endocannabinoid system, this study investigates the acute effects of THC on adult zebrafish behavior and the mechanisms involved. A concentration-dependent THC-induced behavioral stereotypy akin to THC's effect in rats and the psychotropics phencyclidine and ketamine in zebrafish was established. Distinctive circular swimming during THC-exposure was measured using a novel analytical method that we developed, which detected an elevated Repetition Index (RI) compared to vehicle controls. This was reduced upon co-administration of N-methyl-D-aspartate (NMDA) receptor agonist NMDA, suggesting that THC exerts its effects via biochemical or neurobiological mechanisms associated with NMDA receptor antagonism. Co-treatment of gamma-aminobutyric acid receptor antagonist pentylenetetrazol also showed signs of reducing the RI. Since THC-induced repetitive behavior remained in co-administrations with cannabinoid receptor 1 inverse agonist AM251, the phenotype may be cannabinoid receptor 1-independent. Conversely, the inverse cannabinoid receptor 2 agonist AM630 significantly reduced THC-induced behavioral stereotypy, indicating cannabinoid receptor 2 as a possible mediator. A significant reduction of the THC-RI was also observed by the antipsychotic sulpiride. Together, these findings highlight this model's potential for elucidating the mechanistic relationship between Cannabis and psychosis.

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  • 52.
    Dang, Junhua
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Barker, Paul
    Univ Cologne, Social Cognit Ctr Cologne, Cologne, Germany.
    Baumert, Anna
    Max Planck Inst Res Collect Goods, Cologne, Germany; TUM Sch Educ, Munich, Germany.
    Bentvelzen, Margriet
    Univ Amsterdam, Amsterdam Business Sch, Amsterdam, Netherlands.
    Berkman, Elliot
    Univ Oregon, Dept Psychol, Eugene, OR 97403 USA.
    Buchholz, Nita
    Univ Koblenz Landau, Dept Psychol, Koblenz, Germany.
    Buczny, Jacek
    Vrije Univ Amsterdam, Dept Expt & Appl Psychol, Amsterdam, Netherlands.
    Chen, Zhansheng
    Univ Hong Kong, Dept Psychol, Hong Kong, Peoples R China.
    De Cristofaro, Valeria
    Univ Rome Sapienza, Dept Social & Dev Psychol, Rome, Italy.
    de Vries, Lianne
    Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.
    Dewitte, Siegfried
    Katholieke Univ Leuven, Behav Engn Res Grp, Leuven, Belgium.
    Giacomantonio, Mauro
    Gong, Ran
    Beijing Sport Univ, Dept Psychol, Beijing, Peoples R China.
    Homan, Maaike
    Univ Amsterdam, Amsterdam Inst Social Sci Res, Amsterdam, Netherlands.
    Imhoff, Roland
    Johannes Gutenberg Univ Mainz, Social & Legal Psychol, Mainz, Germany.
    Ismail, Ismaharif
    Natl Univ Singapore, Dept Psychol, Singapore, Singapore.
    Jia, Lile
    Natl Univ Singapore, Dept Psychol, Singapore, Singapore.
    Kubiak, Thomas
    Johannes Gutenberg Univ Mainz, Inst Psychol, Mainz, Germany.
    Lange, Florian
    Katholieke Univ Leuven, Behav Engn Res Grp, Leuven, Belgium.
    Li, Dan-yang
    Beijing Sport Univ, Dept Psychol, Beijing, Peoples R China.
    Livingston, Jordan
    Univ Oregon, Dept Psychol, Eugene, OR 97403 USA.
    Ludwig, Rita
    Univ Oregon, Dept Psychol, Eugene, OR 97403 USA.
    Panno, Angelo
    European Univ Rome, Dept Human Sci, Rome, Italy.
    Pearman, Joshua
    Univ Oregon, Dept Psychol, Eugene, OR 97403 USA.
    Rassi, Niklas
    Univ Hamburg, Inst Psychol, Hamburg, Germany.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Sechenov First Moscow State Med Univ, Inst Translat Med & Biotechnol, Moscow, Russia.
    Schmitt, Manfred
    Univ Koblenz Landau, Dept Psychol, Koblenz, Germany.
    Sevincer, A. Timur
    Univ Hamburg, Inst Psychol, Hamburg, Germany.
    Shi, Jiaxin
    Univ Hong Kong, Dept Psychol, Hong Kong, Peoples R China.
    Stamos, Angelos
    Katholieke Univ Leuven, Behav Engn Res Grp, Leuven, Belgium.
    Tan, Yia Chin
    Natl Univ Singapore, Dept Psychol, Singapore, Singapore.
    Wenzel, Mario
    Johannes Gutenberg Univ Mainz, Inst Psychol, Mainz, Germany.
    Zerhouni, Oulmann
    Univ Paris Nanterre, Laboratoire Parisien Psychol Sociale, Nanterre, France.
    Zhang, Li-wei
    Beijing Sport Univ, Dept Psychol, Beijing, Peoples R China.
    Zhang, Yi-jia
    Beijing Sport Univ, Dept Psychol, Beijing, Peoples R China.
    Zinkernagel, Axel
    A Multilab Replication of the Ego Depletion Effect2021In: Social Psychology and Personality Science, ISSN 1948-5506, E-ISSN 1948-5514, Vol. 12, no 1, p. 14-24Article in journal (Refereed)
    Abstract [en]

    There is an active debate regarding whether the ego depletion effect is real. A recent preregistered experiment with the Stroop task as the depleting task and the antisaccade task as the outcome task found a medium-level effect size. In the current research, we conducted a preregistered multilab replication of that experiment. Data from 12 labs across the globe (N = 1,775) revealed a small and significant ego depletion effect, d = 0.10. After excluding participants who might have responded randomly during the outcome task, the effect size increased to d = 0.16. By adding an informative, unbiased data point to the literature, our findings contribute to clarifying the existence, size, and generality of ego depletion.

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  • 53.
    Dang, Junhua
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Ekim, Zeynep E.
    Lund Univ, Fac Social Sci, Dept Psychol, Lund, Sweden..
    Ohlsson, Sarah
    Lund Univ, Fac Social Sci, Dept Psychol, Lund, Sweden..
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Sechenov First Moscow State Med Univ, Inst Translat Med & Biotechnol, Moscow, Russia..
    Is there prejudice from thin air?: Replicating the effect of emotion on automatic intergroup attitudes2020In: BMC Psychology, E-ISSN 2050-7283, Vol. 8, no 1, article id 47Article in journal (Refereed)
    Abstract [en]

    Background: Previous studies showed that anger, rather than sadness, created automatic intergroup bias in a minimal group context. Methods: The current research reports a single study (N=99) aiming to replicate this finding and further to test whether the intergroup bias manifests as in group favoritism, outgroup derogation, or both. Results: Our results failed to replicate the effect of anger on automatic bias. Intriguingly, participants across all emotion conditions exhibited high level of ingroup favoritism, but there was little evidence of outgroup derogation. Conclusion: These results suggest that, when there is no competition or conflict between groups, individuals, even in a bad emotional state such as anger, generally show ingroup love rather than outgroup hate.

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  • 54.
    Dang, Junhua
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Hagger, Martin S.
    Univ Calif Merced, Dept Psychol Sci, Merced, CA USA;Univ Jyvaskyla, Fac Sport & Hlth Sci, Jyvaskyla, Finland;Univ Calif Merced, Sch Social Sci Humanities & Arts, Psychol Sci, 5200 N Lake Rd, Merced, CA 95343 USA.
    Time to Set a New Research Agenda for Ego Depletion and Self-Control2019In: Social Psychology, ISSN 1864-9335, E-ISSN 2151-2590, Vol. 50, no 5-6, p. 277-281Article in journal (Other academic)
  • 55.
    Dang, Junhua
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    King, Kevin M.
    Univ Washington, Dept Psychol, Seattle, WA 98195 USA.
    Inzlicht, Michael
    Univ Toronto, Dept Psychol, Toronto, ON, Canada;Univ Toronto, Rotman Sch Management, Toronto, ON, Canada.
    Why Are Self-Report and Behavioral Measures Weakly Correlated?2020In: Trends in cognitive sciences, ISSN 1364-6613, E-ISSN 1879-307X, Vol. 24, no 4, p. 267-269Article in journal (Refereed)
    Abstract [en]

    Accumulating evidence indicates weak correlations between self-report and behavioral measures of the same construct. We suggest that these weak correlations result from the poor reliability of many behavioral measures and the distinct response processes involved in the two measurement types. We also describe how researchers can benefit from appropriate use of these measures.

  • 56.
    Dang, Junhua
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Liu, Xiaoping
    Peking Univ, Sch Psychol & Cognit Sci, Beijing, Peoples R China.;Peking Univ, Beijing Key Lab Behav & Mental Hlth, Beijing, Peoples R China..
    Xiao, Shanshan
    Stockholm Univ, Dept Psychol, Stockholm, Sweden..
    Mao, Lihua
    Peking Univ, Sch Psychol & Cognit Sci, Beijing, Peoples R China.;Peking Univ, Beijing Key Lab Behav & Mental Hlth, Beijing, Peoples R China..
    Chan, Ka Tung
    Columbia Univ, Dept Psychol, New York, NY 10027 USA..
    Li, Chaoyu
    City Univ Hong Kong, Dept Social & Behav Sci, Kowloon Tong, Hong Kong, Peoples R China..
    Lin, Meihan
    Lund Univ, Dept Psychol, Lund, Sweden..
    Liu, Zanzan
    Lund Univ, Dept Psychol, Lund, Sweden..
    Luo, Yanran
    City Univ Hong Kong, Dept Social & Behav Sci, Kowloon Tong, Hong Kong, Peoples R China..
    Sun, Yumingzi
    Lund Univ, Dept Psychol, Lund, Sweden..
    Wu, Yu-Hsin
    Lund Univ, Dept Psychol, Lund, Sweden..
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Sechenov First Moscow State Med Univ, Inst Translat Med & Biotechnol, Moscow, Russia..
    The Beauty of the Zero: Replications and Extensions of the Hidden-Zero Effect in Delay Discounting Tasks2021In: Social Psychology and Personality Science, ISSN 1948-5506, E-ISSN 1948-5514, Vol. 12, no 4, p. 544-549Article in journal (Refereed)
    Abstract [en]

    Unlike the presentation format in a typical delay discounting task (e.g., "Would you prefer [A] US$4.3 today OR [B] US$7.5 in 22 days?"), Magen et al. inserted a zero to each alternative (e.g., "Would you prefer [A] US$4.3 today and US$0 in 22 days OR [B] US$0 today and US$7.5 in 22 days?") and found this manipulation effectively reduced delay discounting (d= .84), which was referred to as the hidden-zero effect. Study 1 was a direct replication of this effect. In Study 2, we tested whether the explicit-zero format could buffer against the detrimental effect of exposure to sexy cues on delay discounting. In Study 3, we explored the mechanism underlying the hidden-zero effect. Taken together, the hidden-zero effect was consistently found across all studies (N= 2,440) and our internal meta-analysis yielded a medium to large effect size (d= .52).

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  • 57.
    de Jorge Martínez, Clara
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Rukh, Gull
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Williams, Michael J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Gaudio, Santino
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy..
    Brooks, Samantha
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. School of Psychology, Faculty of Health, Liverpool John Moores University, UK; Department of Psychology, School of Human and Community Development, University of the Witwatersrand, Johannesburg, South Africa..
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Institute for Translational Medicine and Biotechnology, Sechenov First Moscow State Medical University, Moscow, Russia..
    Genetics of anorexia nervosa: An overview of genome-wide association studies and emerging biological links2022In: Journal of genetics and genomics = Yi chuan xue bao, ISSN 1673-8527, Vol. 49, no 1, p. 1-12, article id S1673-8527(21)00320-9Article, review/survey (Refereed)
    Abstract [en]

    Anorexia nervosa (AN) is a complex disorder with a strong genetic component. Comorbidities are frequent and there is substantial overlap with other disorders. The lack of understanding of the molecular and neuroanatomical causes has made it difficult to develop effective treatments and it is often difficult to treat in clinical practice. Recent advances in genetics have changed our understanding of polygenic diseases, increasing the possibility of understanding better how molecular pathways are intertwined. This review synthetizes the current state of genetic research providing an overview of genome-wide association studies (GWAS) findings in AN as well as overlap with other disorders, traits, pathways, and imaging results. This paper also discusses the different putative global pathways that are contributing to the disease including the evidence for metabolic and psychiatric origin of the disease.

  • 58.
    de la Villarmois, Emilce
    et al.
    Univ Nacl Cordoba, Fac Ciencias Quim, Dept Farmacol, IFEC CONICET, Haya de la Torre & Medina Allende, RA-5000 Cordoba, Argentina.
    Gabach, Laura A.
    Univ Nacl Cordoba, Fac Ciencias Quim, Dept Farmacol, IFEC CONICET, Haya de la Torre & Medina Allende, RA-5000 Cordoba, Argentina.
    Bianconi, Santiago
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. UNC, Inst Fisiol, Fac Ciencias Med, INICSA CONICET, Cordoba, Argentina.
    Poretti, Maria Belen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. UNC, Inst Fisiol, Fac Ciencias Med, INICSA CONICET, Cordoba, Argentina.
    Occhieppo, Victoria
    Univ Nacl Cordoba, Fac Ciencias Quim, Dept Farmacol, IFEC CONICET, Haya de la Torre & Medina Allende, RA-5000 Cordoba, Argentina.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Carlini, Valeria P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. UNC, Inst Fisiol, Fac Ciencias Med, INICSA CONICET, Cordoba, Argentina.
    Perez, Mariela Fernanda
    Univ Nacl Cordoba, Fac Ciencias Quim, Dept Farmacol, IFEC CONICET, Haya de la Torre & Medina Allende, RA-5000 Cordoba, Argentina.
    Pharmacological NOS-1 Inhibition Within the Hippocampus Prevented Expression of Cocaine Sensitization: Correlation with Reduced Synaptic Transmission2020In: Molecular Neurobiology, ISSN 0893-7648, E-ISSN 1559-1182, Vol. 57, no 1, p. 450-460Article in journal (Refereed)
    Abstract [en]

    Behavioral sensitization to psychostimulants hyperlocomotor effect is a useful model of addiction and craving. Particularly, cocaine sensitization in rats enhanced synaptic plasticity within the hippocampus, an important brain region for the associative learning processes underlying drug addiction. Nitric oxide (NO) is a neurotransmitter involved in both, hippocampal synaptic plasticity and cocaine sensitization. It has been previously demonstrated a key role of NOS-1/NO/sGC/cGMP signaling pathway in the development of cocaine sensitization and in the associated enhancement of hippocampal synaptic plasticity. The aim of the present investigation was to determine whether NOS-1 inhibition after development of cocaine sensitization was able to reverse it, and to characterize the involvement of the hippocampus in this phenomenon. Male Wistar rats were administered only with cocaine (15 mg/kg/day i.p.) for 5 days. Then, animals received 7-nitroindazole (NOS-1 inhibitor) either systemically for the next 5 days or a single intra-hippocampal administration. Development of sensitization and its expression after withdrawal were tested, as well as threshold for long-term potentiation in hippocampus, NOS-1, and CREB protein levels and gene expression. The results showed that NOS-1 protein levels and gene expression were increased only in sensitized animals as well as CREB gene expression. NOS-1 inhibition after sensitization reversed behavioral expression and the highest level of hippocampal synaptic plasticity. In conclusion, NO signaling within the hippocampus is critical for the development and expression of cocaine sensitization. Therefore, NOS-1 inhibition or NO signaling pathways interferences during short-term withdrawal after repeated cocaine administration may represent plausible pharmacological targets to prevent or reduce susceptibility to relapse.

  • 59.
    Desai Boström, Adrian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Epigenetic dysregulation in relation to psychiatric traits in adolescence and adulthood2021Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Epigenetics has evolved into a key research focus in the field of psychiatry. DNA methylation is the most researched epigenetic mechanism. In paper I-III, 130 and 93 adolescents were randomly recruited at two separate intervals. Subjects were evaluated by web-based diagnostic interviews using the Development and Well-Being Assessment (DAWBA), providing computer generated diagnostic predictions of probability of diagnosis, covering several psychiatric disorders. For Paper I-II, the genome-wide DNA methylation pattern was measured from whole blood using the Illumina 450K array, and for paper IV by the Illumina EPIC BeadChip. In paper I, a methylome-wide association study (MWAS) was conducted (n=93) followed by a validation analysis (n=78), contrasting methylation levels in groups stratified by DAWBA depression risk scores. A microRNA4646 (MIR4646) associated methylation locus was differentially methylated in the MWAS (pbonf<0.05) and results were replicated in the validation cohort (p<0.05). Methylation levels at the identified locus correlated inversely with gene expression levels of MIR4456 (p<0.05). In silico analysis suggests MIR4646 may influence synthesis of omega-3 fatty acids, previously implicated in major depressive disorder. In paper II, 37 single nucleotide polymorphisms (SNP:s) previously associated with psychiatric disease were evaluated in relation to genome-wide DNA methylation levels in 130 adolescents in a methylome-wide (mQTL) analysis. Five SNP-CpG pairs were identified (pbonf<0.05) and replicated (p<0.05). Methylation of three of these were shown to be significantly correlated with gene expression levels of the associated genes (p<0.05). One identified GAD1-coupled methylation site was differentially methylated to a general psychiatric risk score in adolescents (p<0.05). In Paper III, hypothalamic-pituitary-adrenal (HPA)-axis coupled DNA methylation loci were investigated in 88 suicide attempters to identify associations to severity of suicide attempt. One corticotropin releasing hormone (CRH)-associated CpG-site was significantly hypomethylated in the high-risk group of suicide-attempters (n=31)(cg19035496, p<0.001) and exhibited hypermethylation in an external study group of adolescents in dependency of a general psychiatric risk score (p<0.05). In paper IV, 8,852 microRNA (miRNA) associated CpG-sites were investigated for an association with hypersexual disorder (HD). A microRNA-4456 (MIR4456) associated CpG-site (cg01299774) was borderline significant in HD (pFDR=5.81E-02) and differentially methylated in alcohol dependence (p<0.05) in an independent study group. Methylation levels at cg01299774 correlated inversely with expression levels of MIR4456 (p<0.01) and MIR4456 was lower expressed in HD (p<0.05). In-silico analyses suggests MIR4456 putatively targets genes preferentially expressed in brain and that are involved in major neuronal molecular mechanisms thought to be relevant for HD, e.g., the oxytocin signaling pathway.

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  • 60.
    Dyakova, Olga
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Nordström: Motion Vision.
    Rångtell, Frida H
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Tan, Xiao
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Nordström, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Nordström: Motion Vision. Centre for Neuroscience, Flinders University, Adelaide, South Australia, Australia.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Acute sleep loss induces signs of visual discomfort in young men2019In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 28, no 6, article id e12837Article in journal (Refereed)
    Abstract [en]

    Acute sleep loss influences visual processes in humans, such as recognizing facial emotions. However, to the best of our knowledge, no study till date has examined whether acute sleep loss alters visual comfort when looking at images. One image statistic that can be used to investigate the level of visual comfort experienced under visual encoding is the slope of the amplitude spectrum, also referred to as the slope constant. The slope constant describes the spatial distribution of pixel intensities and deviations from the natural slope constant can induce visual discomfort. In the present counterbalanced crossover design study, 11 young men with normal or corrected-to-normal vision participated in two experimental conditions: one night of sleep loss and one night of sleep. In the morning after each intervention, subjects performed a computerized psychophysics task. Specifically, they were required to adjust the slope constant of images depicting natural landscapes and close-ups with a randomly chosen initial slope constant until they perceived each image as most natural looking. Subjects also rated the pleasantness of each selected image. Our analysis showed that following sleep loss, higher slope constants were perceived as most natural looking when viewing images of natural landscapes. Images with a higher slope constant are generally perceived as blurrier. The selected images were also rated as less pleasant after sleep loss. No such differences between the experimental conditions were noted for images of close-ups. The results suggest that sleep loss induces signs of visual discomfort in young men. Possible implications of these findings are discussed.

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  • 61.
    Fredriksson, Robert
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Sreedharan, Smitha
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neuro-Oncology.
    Nordenankar, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Alsiö, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Lindberg, Frida A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Hutchinson, Ashley
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Eriksson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Roshanbin, Sahar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Ciuculete, Diana M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Klockars, Anica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Todkar, Aniruddha
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Hägglund, Maria G
    Hellsten, Sofie V
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Hindlycke, Viktoria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Västermark, Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Shevchenko, Ganna
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Olivo, Gaia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    K, Cheng
    Kullander, Klas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Moazzami, Ali
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Olszewski, Pawel K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    The polyamine transporter Slc18b1(VPAT) is important for both short and long time memory and for regulation of polyamine content in the brain.2019In: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 15, no 12, article id e1008455Article in journal (Refereed)
    Abstract [en]

    SLC18B1 is a sister gene to the vesicular monoamine and acetylcholine transporters, and the only known polyamine transporter, with unknown physiological role. We reveal that Slc18b1 knock out mice has significantly reduced polyamine content in the brain providing the first evidence that Slc18b1 is functionally required for regulating polyamine levels. We found that this mouse has impaired short and long term memory in novel object recognition, radial arm maze and self-administration paradigms. We also show that Slc18b1 KO mice have altered expression of genes involved in Long Term Potentiation, plasticity, calcium signalling and synaptic functions and that expression of components of GABA and glutamate signalling are changed. We further observe a partial resistance to diazepam, manifested as significantly lowered reduction in locomotion after diazepam treatment. We suggest that removal of Slc18b1 leads to reduction of polyamine contents in neurons, resulting in reduced GABA signalling due to long-term reduction in glutamatergic signalling.

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  • 62.
    Gabor, Erika
    et al.
    Biol Res Ctr, Inst Genet, Immunol Unit, POB 521, H-6701 Szeged, Hungary..
    Cinege, Gyongyi
    Biol Res Ctr, Inst Genet, Immunol Unit, POB 521, H-6701 Szeged, Hungary..
    Csordas, Gabor
    Biol Res Ctr, Inst Genet, Immunol Unit, POB 521, H-6701 Szeged, Hungary.;Univ Cologne, Inst Genet, D-50931 Cologne, Germany.;Univ Cologne, Cologne Excellence Cluster Cellular Stress Respon, D-50931 Cologne, Germany..
    Rusvai, Miklos
    Univ Vet Med, Istvan U 2, H-1078 Budapest, Hungary..
    Honti, Viktor
    Biol Res Ctr, Inst Genet, Immunol Unit, POB 521, H-6701 Szeged, Hungary..
    Kolics, Balazs
    Univ Pannonia, Georgikon Fac, Dept Plant Sci & Biotechnol, Deak Fu 16, H-8360 Keszthely, Hungary..
    Torok, Tibor
    Univ Szeged, Dept Genet, Kozep Fasor 52, H-6726 Szeged, Hungary..
    Williams, Michael J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Kurucz, Eva
    Biol Res Ctr, Inst Genet, Immunol Unit, POB 521, H-6701 Szeged, Hungary..
    Ando, Istvan
    Biol Res Ctr, Inst Genet, Immunol Unit, POB 521, H-6701 Szeged, Hungary..
    Identification of reference markers for characterizing honey bee (Apis mellifera) hemocyte classes2020In: Developmental and Comparative Immunology, ISSN 0145-305X, E-ISSN 1879-0089, Vol. 109, article id 103701Article in journal (Refereed)
    Abstract [en]

    Cell mediated immunity of the honey bee (Apis mellifera) involves the activity of several hemocyte populations, currently defined by morphological features and lectin binding characteristics. The objective of the present study was to identify molecular markers capable of characterizing subsets of honey bee hemocytes. We developed and employed monoclonal antibodies with restricted reactions to functionally distinct hemocyte subpopulations. Melanizing cells, known as oenocytoids, were defined by an antibody to prophenoloxidase, aggregating cells were identified by the expression of Hemolectin, and phagocytic cells were identified by a marker expressed on granulocytes. We anticipate that this combination of antibodies not only allows for the detection of functionally distinct hemocyte subtypes, but will help to further the exploration of hematopoietic compartments, as well as reveal details of the honey bee cellular immune defense against parasites and microbes.

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  • 63.
    Gandasi, Nikhil R.
    et al.
    Univ Göteborg, Inst Neurosci & Physiol, Dept Metab Physiol, Box 430, SE-40530 Gothenburg, Sweden..
    Arapi, Vasiliki
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Mickael, Michel E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Polish Acad Sci, Inst Genet & Anim Biotechnol, Ul Postepu 36A, PL-05552 Jastrzebiec, Magdalenka, Poland..
    Belekar, Prajakta A.
    Univ Göteborg, Inst Neurosci & Physiol, Dept Metab Physiol, Box 430, SE-40530 Gothenburg, Sweden..
    Granlund, Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Kothegala, Lakshmi
    Univ Göteborg, Inst Neurosci & Physiol, Dept Metab Physiol, Box 430, SE-40530 Gothenburg, Sweden..
    Fredriksson, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Bagchi, Sonchita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Glutamine Uptake via SNAT6 and Caveolin Regulates Glutamine-Glutamate Cycle2021In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 22, no 3, article id 1167Article in journal (Refereed)
    Abstract [en]

    SLC38A6 (SNAT6) is the only known member of the SLC38 family that is expressed exclusively in the excitatory neurons of the brain. It has been described as an orphan transporter with an unknown substrate profile, therefore very little is known about SNAT6. In this study, we addressed the substrate specificity, mechanisms for internalization of SNAT6, and the regulatory role of SNAT6 with specific insights into the glutamate-glutamine cycle. We used tritium-labeled amino acids in order to demonstrate that SNAT6 is functioning as a glutamine and glutamate transporter. SNAT6 revealed seven predicted transmembrane segments in a homology model and was localized to caveolin rich sites at the plasma membrane. SNAT6 has high degree of specificity for glutamine and glutamate. Presence of these substrates enables formation of SNAT6-caveolin complexes that aids in sodium dependent trafficking of SNAT6 off the plasma membrane. To further understand its mode of action, several potential interacting partners of SNAT6 were identified using bioinformatics. Among them where CTP synthase 2 (CTPs2), phosphate activated glutaminase (Pag), and glutamate metabotropic receptor 2 (Grm2). Co-expression analysis, immunolabeling with co-localization analysis and proximity ligation assays of these three proteins with SNAT6 were performed to investigate possible interactions. SNAT6 can cycle between cytoplasm and plasma membrane depending on availability of substrates and interact with Pag, synaptophysin, CTPs2, and Grm2. Our data suggest a potential role of SNAT6 in glutamine uptake at the pre-synaptic terminal of excitatory neurons. We propose here a mechanistic model of SNAT6 trafficking that once internalized influences the glutamate-glutamine cycle in presence of its potential interacting partners.

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  • 64.
    Gaudio, Santino
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Univ Campus Biomed Roma, Area Diagnost Imaging, Ctr Integrated Res, Rome, Italy.
    Carducci, Filippo
    Sapienza Univ, Neuroimaging Lab, Dept Physiol & Pharmacol, Rome, Italy.
    Piervincenzi, Claudia
    Sapienza Univ, Neuroimaging Lab, Dept Physiol & Pharmacol, Rome, Italy.
    Olivo, Gaia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Sechenov First Moscow State Med Univ, Inst Translat Med & Biotechnol, Moscow, Russia.
    Altered thalamo-cortical and occipital-parietal-temporal-frontal white matter connections in patients with anorexia and bulimia nervosa: a systematic review of diffusion tensor imaging studies2019In: Journal of Psychiatry & Neuroscience, ISSN 1180-4882, E-ISSN 1488-2434, Vol. 44, no 5, p. 324-339Article, review/survey (Refereed)
    Abstract [en]

    Background: Anorexia nervosa and bulimia nervosa are complex mental disorders, and their etiology is still not fully understood. This paper reviews the literature on diffusion tensor imaging studies in patients with anorexia nervosa and bulimia nervosa to explore the usefulness of white matter microstructural analysis in understanding the pathophysiology of eating disorders.

    Methods: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify diffusion tensor imaging studies that compared patients with an eating disorder to control groups. We searched relevant databases for studies published from database inception to August 2018, using combinations of select keywords. We categorized white matter tracts according to their 3 main classes: projection (i.e., thalamo-cortical), association (i.e., occipital-parietal-temporal-frontal) and commissural (e.g., corpus callosum).

    Results: We included 19 papers that investigated a total of 427 participants with current or previous eating disorders and 444 controls. Overall, the studies used different diffusion tensor imaging approaches and showed widespread white matter abnormalities in patients with eating disorders. Despite differences among the studies, patients with anorexia nervosa showed mainly white matter microstructural abnormalities of thalamo-cortical tracts (i.e., corona radiata, thalamic radiations) and occipital-parietal-temporal-frontal tracts (i.e., left superior longitudinal and inferior fronto-occipital fasciculi). It was less clear whether white matter alterations persist after recovery from anorexia nervosa. Available data on bulimia nervosa were partially similar to those for anorexia nervosa.

    Limitations: Study sample composition and diffusion tensor imaging analysis techniques were heterogeneous. The number of studies on bulimia nervosa was too limited to be conclusive.

    Conclusion: White matter microstructure appears to be affected in anorexia nervosa, and these alterations may play a role in the pathophysiology of this eating disorder. Although we found white matter alterations in bulimia nervosa that were similar to those in anorexia nervosa, white matter changes in bulimia nervosa remain poorly investigated, and these findings were less conclusive. Further studies with longitudinal designs and multi-approach analyses are needed to better understand the role of white matter changes in eating disorders.

  • 65.
    Gentreau, Mélissa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Functional Pharmacology and Neuroscience.
    Rukh, Gull
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Functional Pharmacology and Neuroscience.
    Miguet, Maud
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Functional Pharmacology and Neuroscience.
    Clemensson, Laura E
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Functional Pharmacology and Neuroscience.
    Alsehli, Ahmed M
    Titova, Olga E
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Medical epidemiology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    The effects of statins on cognitive performance are mediated by low-density lipoprotein, C-reactive protein and blood glucose concentrations.2023In: The journals of gerontology. Series A, Biological sciences and medical sciences, ISSN 1079-5006, E-ISSN 1758-535X, article id glad163Article in journal (Refereed)
    Abstract [en]

    Statins are widely used for cardiovascular disease prevention but their effects on cognition remain unclear. Statins reduce cholesterol concentration and have been suggested to provide both beneficial and detrimental effects. Our aim was to investigate the cross-sectional and longitudinal association between statin use and cognitive performance, and whether blood low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, glucose, C-Reactive Protein (CRP), and vitamin D biomarkers mediated this association. We used participants from the UK biobank aged 40 to 69 without neurological and psychiatric disorders (n = 147,502 and n = 24,355, respectively). We performed linear regression to evaluate the association between statin use and cognitive performance and, mediation analysis to quantify the total, direct, indirect effects and the proportion meditated by blood biomarkers. Statin use was associated with lower cognitive performance at baseline (β = -0.40 [-0.53, -0.28], P = <.0001) and this association was mediated by LDL (Proportion mediated = 51.4%, P = 0.002), CRP (Proportion mediated = -11%, P = 0.006) and blood glucose (Proportion mediated = 2.6%, P = 0.018) concentrations. However, statin use was not associated with cognitive performance, measured 8 years later (β = -0.003 [-0.11, 0.10], P = 0.96). Our findings suggest that statins are associated with lower short-term cognitive performance by lowering LDL and raising blood glucose concentrations, and better performance by lowering CRP concentrations. In contrast, statins have no effect on long-term cognition and remain beneficial in reducing cardiovascular risk factors.

  • 66.
    Herrera, Guadalupe
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Univ Nacl Cordoba, Fac Ciencias Quim, Dept Farmacol, IFEC CONICET, Haya de la Torre & Medina Allende Ciudad Univ, RA-5000 Cordoba, Argentina.
    Calfa, Gaston
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Univ Nacl Cordoba, Fac Ciencias Quim, Dept Farmacol, IFEC CONICET, Haya de la Torre & Medina Allende Ciudad Univ, RA-5000 Cordoba, Argentina.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Sechenov First Moscow State Med Univ, Inst Translat Med & Biotechnol, Moscow, Russia.
    Lasaga, Mercedes
    Inst Invest Biomed INBIOMED UBA CONICET, Fac Med, Buenos Aires, DF, Argentina.
    Scimonelli, Teresa
    Univ Nacl Cordoba, Fac Ciencias Quim, Dept Farmacol, IFEC CONICET, Haya de la Torre & Medina Allende Ciudad Univ, RA-5000 Cordoba, Argentina.
    Memory consolidation impairment induced by Interleukin-1 beta is associated with changes in hippocampal structural plasticity2019In: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 370, article id 111969Article in journal (Refereed)
    Abstract [en]

    Pro-inflammatory cytokines, particularly Interleukin-1 beta (IL-1 beta), can affect cognitive processes such as learning and memory. The aim of this study was to establish whether the effect of IL-1 beta on contextual fear memory is associated with changes in hippocampal structural plasticity. We also studied the effect of alpha-melanocyte-stimulating hormone (alpha-MSH), a potent anti-inflammatory and neuro-protective peptide. Different groups of animals were implanted bilaterally in dorsal hippocampus (DH). After recovery they were conditioned for contextual fear memory and received the different treatments (vehicle, IL-1 beta, alpha-MSH or IL-1 beta + alpha-MSH). Memory was assessed 24 hs after conditioning and immediately after rats were perfused for dendritic spine analysis. Our results show that local hippocampal administration of IL-1 beta just after memory encoding induced impairment in contextual memory and a reduction in the total density of CA1 hippocampal dendritic spines, particularly the mature ones. alpha-MSH administration reversed the IL-1 beta induced changes. The results suggest that neuro-inflammation induced by IL-1 beta interferes with experience-dependent structural plasticity in DH whereas alpha-MSH has a beneficial modulatory role in preventing this effect.

  • 67.
    Jamshidnejad-Tosaramandani, Tahereh
    et al.
    Razi Univ, Nanobiotechnol Dept, Fac Innovat Sci & Technol, Kermanshah, Iran.;Razi Univ, Dept Biol, Fac Sci, Kermanshah, Iran.;Uppsala Univ, Dept Surg Sci, Funct Pharmacol & Neurosci, Uppsala, Sweden..
    Kashanian, Soheila
    Razi Univ, Nanobiotechnol Dept, Fac Innovat Sci & Technol, Kermanshah, Iran.;Razi Univ, Fac Chem, Sensor & Biosensor Res Ctr SBRC, Kermanshah, Iran..
    Al-Sabri, Mohamed H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Krocianova, Daniela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Clemensson, Laura Emily
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Gentreau, Melissa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Functional Pharmacology and neuroscience.
    Statins and cognition: Modifying factors and possible underlying mechanisms2022In: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 14, article id 968039Article, review/survey (Refereed)
    Abstract [en]

    Statins are a class of widely prescribed drugs used to reduce low-density lipoprotein cholesterol (LDL-C) and important to prevent cardiovascular diseases (CVD). Most statin users are older adults with CVD, who are also at high risk of cognitive decline. It has been suggested that statins can alter cognitive performance, although their positive or negative effects are still debated. With more than 200 million people on statin therapy worldwide, it is crucial to understand the reasons behind discrepancies in the results of these studies. Here, we review the effects of statins on cognitive function and their association with different etiologies of dementia, and particularly, Alzheimer's disease (AD). First, we summarized the main individual and statin-related factors that could modify the cognitive effects of statins. Second, we proposed the underlying mechanisms for the protective and adverse effects of statins on cognitive performance. Finally, we discussed potential causes of discrepancies between studies and suggested approaches to improve future studies assessing the impact of statins on dementia risk and cognitive function.

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  • 68.
    Jamshidnejad-Tosaramandani, Tahereh
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Razi Univ, Fac Innovat Sci & Technol, Nanobiotechnol Dept, Kermanshah 6714414971, Iran; Razi Univ, Dept Biol, Fac Sci, Kermanshah 6714414971, Iran.
    Kashanian, Soheila
    Razi Univ, Fac Innovat Sci & Technol, Nanobiotechnol Dept, Kermanshah 6714414971, Iran.;Kermanshah Univ Med Sci, Hlth Technol Inst, Nano Drug Delivery Res Ctr, Kermanshah 6734667149, Iran.;Razi Univ, Sensor & Biosensor Res Ctr SBRC, Fac Chem, Kermanshah 6714414971, Iran..
    Babaei, Mahsa
    Razi Univ, Dept Biol, Fac Sci, Kermanshah 6714414971, Iran..
    Al-Sabri, Mohamed
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. IM Sechenov First Moscow State Med Univ, Inst Translat Med & Biotechnol, Trubetskay Str 8,Bldg 2, Moscow 119991, Russia.
    The Potential Effect of Insulin on AChE and Its Interactions with Rivastigmine In Vitro2021In: Pharmaceuticals, E-ISSN 1424-8247, Vol. 14, no 11, article id 1136Article in journal (Refereed)
    Abstract [en]

    There is no definite cure for Alzheimer's disease (AD) due to its multifactorial origin. Drugs that inhibit acetylcholinesterase (AChE), such as rivastigmine, are promising symptomatic treatments for AD. Emerging evidence suggests that insulin therapy can hinder several aspects of AD pathology. Insulin has been shown to modify the activity of AChE, but it is still unknown how insulin and AChE interact. Combination therapy, which targets several features of the disease based on existing medications, can provide a worthy therapy option for AD management. However, to date, no studies have examined the potential interaction of insulin with AChE and/or rivastigmine in vitro. In the present study, we employed the Response Surface Methodology (RSM) as an in vitro assessment to investigate the effect of insulin on both AChE activity and rivastigmine inhibitory action using a common spectrophotometric assay for cholinesterase activity, Ellman's method. Our results showed that insulin, even at high concentrations, has an insignificant effect on both the activity of AChE and rivastigmine's inhibitory action. The variance of our data is near zero, which means that the dispersion is negligible. However, to improve our understanding of the possible interaction of insulin and rivastigmine, or its target AChE, more in silico modelling and in vivo studies are needed.

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  • 69.
    Jatkowska, Natalia
    et al.
    Gdansk Univ Technol, Dept Analyt Chem, Fac Chem, 11-12 Narutowicza Str, PL-80233 Gdansk, Poland..
    Kudlak, Blazej
    Gdansk Univ Technol, Dept Analyt Chem, Fac Chem, 11-12 Narutowicza Str, PL-80233 Gdansk, Poland..
    Lewandowska, Patrycja
    Gdansk Univ Technol, Dept Analyt Chem, Fac Chem, 11-12 Narutowicza Str, PL-80233 Gdansk, Poland..
    Liu, Wen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Williams, Michael J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. IM Sechenov First Moscow State Med Univ, Inst Translat Med & Biotechnol, Moscow, Russia..
    Identification of synergistic and antagonistic actions of environmental pollutants: Bisphenols A, S and F in the presence of DEP, DBP, BADGE and BADGE center dot 2HCl in three component mixtures2021In: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 767, article id 144286Article in journal (Refereed)
    Abstract [en]

    Ecosystems are facing increased pressure due to the emission of many classes of emerging contaminants. However, very little is known about the interactions of these pollutants, such as bisphenols (BPs), plasticizers or pharmaceuticals. By employing bioluminescent bacteria (Microtox assay), we were able to define interactions between selected emerging pollutants (namely BPA, BPS, BPF, BADGE, BADGE center dot 2HCl, DEP, DBP) in ternary mixtures, at environmentally relevant concentration levels (down to as low as 1.89, 1.42. 3.08, and 0.3261AM for, respectively, BPA BPF, BPS and BADGE- 2HCl). We provide the first systematic analysis of bisphenols and phthalates in three component mixtures. Using this system, we performed toxicity modelling with concentration addition (CA) and independent action (IA) approaches, followed by data interpretation using Model Deviation Ratio (MDR) evaluation. Interestingly, we mathematically and experimentally confirmed a novel synergy between BPA, BADGE and BADGE center dot 2HCl. The synergy of BPA, BADGE and BADGE center dot 2HCl is distinct, with both models suggesting these a nalytes have a similar mode of action (MOA). Moreover, we unexpectedly found a strong antagonistic impact with DEP, in mixtures containing BPA and BADGE analogues, which is confirmed with both mathematical models. Our study also shows that the impact of BPS and BPF in many mixtures is highly concentration dependent, justifying the necessity to perform mixture studies using wide concentration ranges. Overall, this study demonstrates that bioluminescent bacteria are a relevant model for detecting the synergistic and antagonist actions of environmental pollutants in mixtures, and highlights the importance of analyzing combinations of pollutants in higher order mixtures.

  • 70.
    Johansson, Anton
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Mohamed, Mohamed S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Moulin, Thiago
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Sechenov First Moscow State Med Univ, Inst Translat Med & Biotechnol, Moscow, Russia..
    Neurological manifestations of COVID-19: A comprehensive literature review and discussion of mechanisms2021In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 358, article id 577658Article, review/survey (Refereed)
    Abstract [en]

    Several neurological symptoms and complications have been described in association with COVID-19, such as anosmia, ageusia, encephalitis and Guillain-Barre ' syndrome. Here, we review the literature describing SARSCoV-2-induced neurological manifestations and provide a comprehensive discussion of proposed mechanisms underlying the neurological pathophysiology. First, we analyse the neuroinvasiveness potential of the coronavirus family based on previous SARS-CoV-1 studies. Then, we describe the current evidence on COVID-19induced nervous tissue damage, including processes behind brain vasculopathy and cytokine storm. We also discuss in detail anosmia and Guillain-Barre ' syndrome. Finally, we provide a summarised timeline of the main findings in the field. Future perspectives are presented, and suggestions of further investigations to clarify how SARS-COV-2 can affect the CNS.

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  • 71.
    Kanders, Sofia H.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Pisanu, Claudia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
    Bandstein, Marcus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Jonsson, Jörgen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Castelao, Enrique
    Pistis, Giorgio
    Gholam-Rezaee, Mehdi
    Eap, Chin B.
    Preisig, Martin
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Institute for Translational Medicine and Biotechnology, Sechenov First Moscow State Medical University, Moscow, Russia.
    Mwinyi, Jessica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    A pharmacogenetic risk score for the evaluation of major depression severity under treatment with antidepressants2020In: Drug development research, ISSN 0272-4391, E-ISSN 1098-2299, Vol. 81, no 1, p. 102-113Article in journal (Refereed)
    Abstract [en]

    The severity of symptoms as well as efficacy of antidepressants in major depressive disorder (MDD) is modified by single nucleotide polymorphisms (SNPs) in different genes, which may contribute in an additive or synergistic fashion. We aimed to investigate depression severity in participants with MDD under treatment with antidepressants in relation to the combinatory effect of selected genetic variants combined using a genetic risk score (GRS). The sample included 150 MDD patients on regular AD therapy from the population‐based Swiss PsyCoLaus cohort. We investigated 44 SNPs previously associated with antidepressant response by ranking them with regard to their association to the Center for Epidemiologic Studies Short Depression Scale (CES‐D) score using random forest. The three top scoring SNPs (rs12248560, rs878567, rs17710780) were subsequently combined into an unweighted GRS, which was included in linear and logistic regression models using the CES‐D score, occurrence of a major depressive episode (MDE) during follow‐up and regular antidepressant treatment during the 6 months preceding follow‐up assessment as outcomes. The GRS was associated with MDE occurrence (p = .02) and ln CES‐D score (p = .001). The HTR1A rs878567 variant was associated with ln CES‐D after adjustment for demographic and clinical variables [p = .02, lower scores for minor allele (G) carriers]. Additionally, rs12248560 (CYP2C19 ) CC homozygotes showed a six‐fold higher likelihood of regular AD therapy at follow‐up compared to minor allele homozygotes [TT; ultrarapid metabolizers (p = .03)]. Our study suggests that the cumulative consideration of pharmacogenetic risk variants more reliably reflects the impact of the genetic background on depression severity than individual SNPs.

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  • 72.
    Klyucherev, Timofey O.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Schiöth: Functional Pharmacology. IM Sechenov First Moscow State Med Univ, Inst Pharm, Dept Pharmacol, Moscow, Russia..
    Olszewski, Pawel K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Schiöth: Functional Pharmacology.
    Shalimova, Alena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Schiöth: Functional Pharmacology. IM Sechenov First Moscow State Med Univ, Inst Pharm, Dept Pharmacol, Moscow, Russia..
    Chubarev, Vladimir N.
    IM Sechenov First Moscow State Med Univ, Inst Translat Med & Biotechnol, Moscow, Russia..
    Tarasov, Vadim V.
    IM Sechenov First Moscow State Med Univ, Inst Pharm, Dept Pharmacol, Moscow, Russia.;IM Sechenov First Moscow State Med Univ, Inst Translat Med & Biotechnol, Moscow, Russia..
    Attwood, Misty M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Schiöth: Functional Pharmacology.
    Syvänen, Stina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Schiöth: Functional Pharmacology.
    Advances in the development of new biomarkers for Alzheimer's disease2022In: Translational Neurodegeneration, ISSN 2047-9158, Vol. 11, no 1, article id 25Article, review/survey (Refereed)
    Abstract [en]

    Alzheimer's disease (AD) is a complex, heterogeneous, progressive disease and is the most common type of neurodegenerative dementia. The prevalence of AD is expected to increase as the population ages, placing an additional burden on national healthcare systems. There is a large need for new diagnostic tests that can detect AD at an early stage with high specificity at relatively low cost. The development of modern analytical diagnostic tools has made it possible to determine several biomarkers of AD with high specificity, including pathogenic proteins, markers of synaptic dysfunction, and markers of inflammation in the blood. There is a considerable potential in using microRNA (miRNA) as markers of AD, and diagnostic studies based on miRNA panels suggest that AD could potentially be determined with high accuracy for individual patients. Studies of the retina with improved methods of visualization of the fundus are also showing promising results for the potential diagnosis of the disease. This review focuses on the recent developments of blood, plasma, and ocular biomarkers for the diagnosis of AD.

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  • 73.
    Lafta, Muataz S
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Functional Pharmacology and Neuroscience.
    Sokolov, Aleksandr V.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Functional Pharmacology and Neuroscience.
    Landtblom, Anne-Marie
    Ericson, Hans
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Abu Hamdeh, Sami
    Exploring biomarkers in trigeminal neuralgia patients operated with microvascular decompression: A comparison with multiple sclerosis patients and non-neurological controls.2023In: European Journal of Pain, ISSN 1090-3801, E-ISSN 1532-2149Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Trigeminal neuralgia (TN) is a severe facial pain condition often associated with a neurovascular conflict. However, neuroinflammation has also been implicated in TN, as it frequently co-occurs with multiple sclerosis (MS).

    METHODS: We analysed protein expression levels of TN patients compared to MS patients and controls. Proximity Extension Assay technology was used to analyse the levels of 92 proteins with the Multiplex Neuro-Exploratory panel provided by SciLifeLab, Uppsala, Sweden. Serum and CSF samples were collected from TN patients before (n = 33 and n = 27, respectively) and after (n = 28 and n = 8, respectively) microvascular decompression surgery. Additionally, we included samples from MS patients (n = 20) and controls (n = 20) for comparison.

    RESULTS: In both serum and CSF, several proteins were found increased in TN patients compared to either MS patients, controls, or both, including EIF4B, PTPN1, EREG, TBCB, PMVK, FKBP5, CD63, CRADD, BST2, CD302, CRIP2, CCL27, PPP3R1, WWP2, KLB, PLA2G10, TDGF1, SMOC1, RBKS, LTBP3, CLSTN1, NXPH1, SFRP1, HMOX2, and GGT5. The overall expression of the 92 proteins in postoperative TN samples seems to shift towards the levels of MS patients and controls in both serum and CSF, as compared to preoperative samples. Interestingly, there was no difference in protein levels between MS patients and controls.

    CONCLUSIONS: We conclude that TN patients showed increased serum and CSF levels of specific proteins and that successful surgery normalizes these protein levels, highlighting its potential as an effective treatment. However, the similarity between MS and controls challenges the idea of shared pathophysiology with TN, suggesting distinct underlying mechanisms in these conditions.

    SIGNIFICANCE: This study advances our understanding of trigeminal neuralgia (TN) and its association with multiple sclerosis (MS). By analysing 92 protein biomarkers, we identified distinctive molecular profiles in TN patients, shedding light on potential pathophysiological mechanisms. The observation that successful surgery normalizes many protein levels suggests a promising avenue for TN treatment. Furthermore, the contrasting protein patterns between TN and MS challenge prevailing assumptions of similarity between the two conditions and point to distinct pathophysiological mechanisms.

  • 74.
    Lagunas-Rangel, Francisco Alejandro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Department of Genetics and Molecular Biology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), Mexico City, Mexico.
    Deciphering the whale's secrets to have a long life2021In: Experimental Gerontology, ISSN 0531-5565, E-ISSN 1873-6815, Vol. 151, article id 111425Article, review/survey (Refereed)
    Abstract [en]

    Whales are marine creatures known for their enormous size and that live in all the oceans on earth. One of the oldest known organisms is bowhead whales, which can survive up to 200 years, and similarly, other species of whales have shown a remarkable long lifespan. In addition to this, whales are highly resistant to cancer, a disease that is strongly related to aging and the accumulation of damage over time. These two characteristics make whales an interesting model to study and that can provide us with a track both to delay aging and to avoid pathologies associated with it, such as cancer. In the present work, we try to analyze different aspects of whales such as metabolism, hematological and biochemical characteristics, and properties of their genome and transcriptome in order to elucidate possible molecular mechanisms that evolution has provided to these aquatic mammals.

  • 75.
    Lagunas-Rangel, Francisco Alejandro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    G protein-coupled receptors that influence lifespan of human and animal models2022In: Biogerontology (Dordrecht), ISSN 1389-5729, E-ISSN 1573-6768, Vol. 23, no 1, p. 1-19Article, review/survey (Refereed)
    Abstract [en]

    Humanity has always sought to live longer and for this, multiple strategies have been tried with varying results. In this sense, G protein-coupled receptors (GPCRs) may be a good option to try to prolong our life while maintaining good health since they have a substantial participation in a wide variety of processes of human pathophysiology and are one of the main therapeutic targets. In this way, we present the analysis of a series of GPCRs whose activity has been shown to affect the lifespan of animal and human models, and in which we put a special interest in describing the molecular mechanisms involved. Our compilation of data revealed that the mechanisms most involved in the role of GPCRs in lifespan are those that mimic dietary restriction, those related to insulin signaling and the AMPK and TOR pathways, and those that alter oxidative homeostasis and severe and/or chronic inflammation. We also discuss the possibility of using agonist or antagonist drugs, depending on the beneficial or harmful effects of each GPCR, in order to prolong people's lifespan and healthspan.

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  • 76.
    Lagunas-Rangel, Francisco Alejandro
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Department of Genetics and Molecular Biology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), Av. Instituto Politécnico Nacional No. 2508, San Pedro Zacatenco, Gustavo A. Madero, 07360, Mexico City, Mexico.
    Kameyama-Kawabe, Luis Yoshio
    Department of Genetics and Molecular Biology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), Av. Instituto Politécnico Nacional No. 2508, San Pedro Zacatenco, Gustavo A. Madero, 07360, Mexico City, Mexico.
    Bermúdez-Cruz, Rosa María
    Department of Genetics and Molecular Biology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), Av. Instituto Politécnico Nacional No. 2508, San Pedro Zacatenco, Gustavo A. Madero, 07360, Mexico City, Mexico.
    Giardiavirus: an update2021In: Parasitology Research, ISSN 0932-0113, E-ISSN 1432-1955, Vol. 120, no 6, p. 1943-1948Article, review/survey (Refereed)
    Abstract [en]

    Giardiavirus is the only virus that infects Giardia duodenalis, a highly prevalent parasite worldwide, especially in low-income and developing countries. This virus belongs to the Totiviridae family, being a relative of other viruses that infect fungi and protozoa. It has a simple structure with only two proteins encoded in its genome and it appears that it can leave the cell without lysis. All these characteristics make it an interesting study model; however, its research has unfortunately made little progress in recent years. Thus, in this review, we summarize the currently available data on Giardiavirus, from their structure, genome and main proteins, to the uses that have been given to them and the possible health applications for the future.

  • 77.
    Lagunas-Rangel, Francisco Alejandro
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Kudłak, Błażej
    Faculty of Chemistry, Department of Analytical Chemistry, Gdańsk University of Technology, Gdańsk, Poland.
    Liu, Wen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Williams, Michael J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Institute of Translational Medicine and Biotechnology, I. M.
    The potential interaction of environmental pollutants and circadian rhythm regulations that may cause leukemia2022In: Critical reviews in environmental science and technology, ISSN 1064-3389, E-ISSN 1547-6537, Vol. 52, no 22, p. 4094-4112Article, review/survey (Refereed)
    Abstract [en]

    Tumor suppressor genes are highly affected during the development of leukemia, including circadian clock genes. Circadian rhythms constitute an evolutionary molecular machinery involving many genes, such as BMAL1, CLOCK, CRY1, CRY2, PER1, PER2, REV-ERBa, and RORA, for tracking time and optimizing daily life during day-night cycles and seasonal changes. For circulating blood cells many of these genes coordinate their proliferation, output, and function, and therein lies their importance for the development of leukemia. Recent findings suggest that environmental pollutants may affect circadian rhythms and thus affect cancer development and treatment. Such environmental pollutants are often found in mixtures and include benzene, tobacco smoke, pesticides and microplastics. Our understanding of the molecular basis for the interaction mechanisms within complex mixtures is also growing, confirming the plausible occurrence of synergistic (superadditive effect) and antagonistic (cancellation effect) actions of pollutant cocktails. In this work, we discuss the relationship of environmental pollutants and the alteration of circadian rhythms that potentially may cause leukemia. We highlight the need of additional dimensions and perhaps a paradigm shift for future studies in relation to continuously growing magnitude of environmental pollution using multitude of disciplines such as development of high throughput reporter cell lines, other cell screening methods, contaminant measurements in leukemia patients, advanced pharmacology and toxicological measurement of mixtures and highly efficient computer analysis including artificial intelligence, among others.

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  • 78.
    Lagunas-Rangel, Francisco Alejandro
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Liu, Wen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Can Exposure to Environmental Pollutants Be Associated with Less Effective Chemotherapy in Cancer Patients?2022In: International Journal of Environmental Research and Public Health, ISSN 1661-7827, E-ISSN 1660-4601, Vol. 19, no 4, p. 2064-2064Article in journal (Refereed)
    Abstract [en]

    Since environmental pollutants are ubiquitous and many of them are resistant to degradation, we are exposed to many of them on a daily basis. Notably, these pollutants can have harmful effects on our health and be linked to the development of disease. Epidemiological evidence together with a better understanding of the mechanisms that link toxic substances with the development of diseases, suggest that exposure to some environmental pollutants can lead to an increased risk of developing cancer. Furthermore, several studies have raised the role of low-dose exposure to environmental pollutants in cancer progression. However, little is known about how these compounds influence the treatments given to cancer patients. In this work, we present a series of evidences suggesting that environmental pollutants such as bisphenol A (BPA), benzo[a]pyrene (BaP), persistent organic pollutants (POPs), aluminum chloride (AlCl3), and airborne particulatematter may reduce the efficacy of some common chemotherapeutic drugs used in different types of cancer. We discuss the potential underlying molecular mechanisms that lead to the generation of this chemoresistance, such as apoptosis evasion, DNA damage repair, activation of pro-cancer signaling

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  • 79.
    Lagunas-Rangel, Francisco Alejandro
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Niemi, Jenni Viivi Linnea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Kudłak, Błażej
    Gdańsk University of Technology, Faculty of Chemistry, Department of Analytical Chemistry, Gdańsk, Poland.
    Williams, Michael J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Jonsson, Jörgen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Institute of Translational Medicine and Biotechnology, I. M. Sechenov First Moscow State Medical University, Moscow, Russia.
    Role of the synergistic interactions of environmental pollutants in the development of cancer2022In: GeoHealth, E-ISSN 2471-1403, Vol. 6, no 4, article id e2021GH000552Article, review/survey (Refereed)
    Abstract [en]

    There is a growing awareness that the large number of environmental pollutants we are exposed to on a daily basis are causing major health problems. Compared to traditional studies that focus on individual pollutants, there are relatively few studies on how pollutants mixtures interact. Several studies have reported a relationship between environmental pollutants and the development of cancer, even when pollutant levels are below toxicity reference values. The possibility of synergistic interactions between different pollutants could explain how even low concentrations can cause major health problems. These intricate that molecular interactions can occur through a wide variety of mechanisms, and our understanding of the physiological effects of mixtures is still limited. The purpose of this paper is to discuss recent reports that address possible synergistic interactions between different types of environmental pollutants that could promote cancer development. Our literature studies suggest that key biological pathways are frequently implicated in such processes. These include increased production of reactive oxygen species, activation by cytochrome P450, and aryl hydrocarbon receptor signaling, among others. We discuss the need to understand individual pathological vulnerability not only in relation to basic genetics and gene expression, but also in terms of measurable exposure to contaminants. We also mention the need for significant improvements in future studies using a multitude of disciplines, such as the development of high-throughput study models, better tools for quantifying pollutants in cancer patients, innovative pharmacological and toxicological studies, and high-efficiency computer analysis, which allow us to analyze the molecular mechanisms of mixtures.

    Plain Language Summary

    In general, every day we are exposed to many pollutants at the same time, and each pollutant can interact with others in different ways. Notably, two or more pollutants can interact and enhance their effects through a phenomenon called synergy and this would explain why, even at low concentrations, pollutants can have important health effects. Several studies have reported a link between environmental pollutants and cancer. Thus, our review of the literature suggests that synergy phenomena between pollutants can alter key points in cells and facilitate cancer development. Similarly, we mention the complications and needs to assess these complex interactions in subsequent studies.

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  • 80.
    Lagunas-Rangel, Francisco Alejandro
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Department of Genetics and Molecular Biology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), Mexico City, Mexico.
    Yee, Janet
    Department of Biology, Biochemistry and Molecular Biology Program, Trent University, Peterborough, ON, Canada.
    Bermúdez-Cruz, Rosa María
    Department of Genetics and Molecular Biology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), Mexico City, Mexico.
    An update on cell division of Giardia duodenalis trophozoites2021In: Microbiological Research, ISSN 0944-5013, E-ISSN 1618-0623, Vol. 250, article id 126807Article, review/survey (Refereed)
    Abstract [en]

    Giardia duodenalis is a flagellated protozoan that is responsible for many cases of diarrheal disease worldwide and is characterized by its great divergence from the model organisms commonly used in studies of basic cellular processes. The life cycle of Giardia involves an infectious cyst form and a proliferative and mobile trophozoite form. Each Giardia trophozoite has two nuclei and a complex microtubule cytoskeleton that consists of eight flagellar axonemes, basal bodies, the adhesive disc, the funis and the median body. Since the success of Giardia infecting other organisms depends on its ability to divide and proliferate efficiently, Giardia must coordinate its cell division to ensure the duplication and partitioning of both nuclei and the multiple cytoskeletal structures. The purpose of this review is to summarize current knowledge about cell division and its regulation in this protist.

  • 81.
    Lekholm, Emilia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Ceder, Mikaela M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Forsberg, Erica C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Sechenov First Moscow State Med Univ, Inst Translat Med & Biotechnol, Moscow, Russia..
    Fredriksson, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Differentiation of two human neuroblastoma cell lines alters SV2 expression patterns2021In: Cellular & Molecular Biology Letters (Druk), ISSN 1425-8153, E-ISSN 1689-1392, Vol. 26, article id 5Article in journal (Refereed)
    Abstract [en]

    Background: The synaptic vesicle glycoprotein 2 (SV2) family is essential to the synaptic machinery involved in neurotransmission and vesicle recycling. The isoforms SV2A, SV2B and SV2C are implicated in neurological diseases such as epilepsy, Alzheimer's and Parkinson's disease. Suitable cell systems for studying regulation of these proteins are essential. Here we present gene expression data of SV2A, SV2B and SV2C in two human neuroblastoma cell lines after differentiation.

    Methods: Human neuroblastoma cell lines SiMa and IMR-32 were treated for seven days with growth supplements (B-27 and N-2), all-trans-retinoic acid (ATRA) or vasoactive intestinal peptide (VIP) and gene expression levels of SV2 and neuronal targets were analyzed.

    Results: The two cell lines reacted differently to the treatments, and only one of the three SV2 isoforms was affected at a time. SV2B and choline O-acetyltransferase (CHAT) expression was changed in concert after growth supplement treatment, decreasing in SiMa cells while increasing in IMR-32. ATRA treatment resulted in no detected changes in SV2 expression in either cell line while VIP increased both SV2C and dopamine transporter (DAT) in IMR-32 cells.

    Conclusion: The synergistic expression patterns between SV2B and CHAT as well as between SV2C and DAT mirror the connectivity between these targets found in disease models and knock-out animals, although here no genetic alteration was made. These cell lines and differentiation treatments could possibly be used to study SV2 regulation and function.

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  • 82.
    Liu, Wen
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Uppsala Univ, Dept Neurosci, Funct Pharmacol, S-75124 Uppsala, Sweden..
    Cao, Hao
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Kimari, Moses
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Maronitis, Georgios
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Williams, Michael J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Uppsala Univ, Dept Neurosci, Funct Pharmacol, S-75124 Uppsala, Sweden.;Sechenov First Moscow State Med Univ, Inst Translat Med & Biotechnol, Moscow 119991, Russia..
    Multidrug Resistance Like Protein 1 Activity in Malpighian Tubules Regulates Lipid Homeostasis in Drosophila2021In: Membranes, E-ISSN 2077-0375, Vol. 11, no 6, article id 432Article in journal (Refereed)
    Abstract [en]

    Simple Summary Multidrug resistance proteins (MRPs) are important for ion transport, toxin/xenobiotic secretion, and signal transduction. Although studies have been undertaken to understand their physiological function, it is not fully known how MRPs may regulate metabolism. We knocked down the expression of Drosophila multidrug-resistance like protein 1 (MRP) in several tissues central to metabolic regulation. Reducing MRP in Malpighian tubules, the functional equivalent to the human kidney, was sufficient to disrupt metabolic homeostasis, owing to abnormal lipid accumulation, as well as changes in feeding behavior. It also increased oxidative stress resistance in adult flies, possibly due to reduced levels of reactive oxygen species. Multidrug resistance proteins (MRPs), members of the ATP-binding cassette transporter (ABC transporter) family, are pivotal for transporting endo- and xenobiotics, which confer resistance to anticancer agents and contribute to the clearance of oxidative products. However, their function in many biological processes is still unclear. We investigated the role of an evolutionarily conserved MRP in metabolic homeostasis by knocking down the expression of Drosophila multidrug-resistance like protein 1 (MRP) in several tissues involved in regulating metabolism, including the gut, fat body, and Malpighian tubules. Interestingly, only suppression of MRP in the Malpighian tubules, the functional equivalent to the human kidney, was sufficient to cause abnormal lipid accumulation and disrupt feeding behavior. Furthermore, reduced Malpighian tubule MRP expression resulted in increased Hr96 (homolog of human pregnane X receptor) expression. Hr96 is known to play a role in detoxification and lipid metabolism processes. Reduced expression of MRP in the Malpighian tubules also conveyed resistance to oxidative stress, as well as reduced normal levels of reactive oxygen species in adult flies. This study reveals that an evolutionarily conserved MRP is required in Drosophila Malpighian tubules for proper metabolic homeostasis.

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  • 83.
    Liu, Wen
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Cao, Hao
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Liao, Sifang
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Kudlak, Blazej
    Gdansk Univ Technol, Dept Analyt Chem, Fac Chem, Gdansk, Poland.
    Williams, Michael J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. IM Sedenov First Moscow State Med Univ, Inst Translat Med & Biotechnol, Moscow, Russia.
    Dibutyl phthalate disrupts conserved circadian rhythm in Drosophila and human cells2021In: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 783, article id 147038Article in journal (Refereed)
    Abstract [en]

    People are constantly exposed to phthalates, due to their common use in the production of plastics, pharmaceuticals, cosmetics and skin care products. The ability of phthalates to disrupt endocrine signaling, leading to developmental, reproductive and metabolic defects, has been studied, yet how phthalates interfere with these biological functions is still unclear. To uncover DBP interacting molecular pathways, we raised Drosophila melanogaster on food containing dibutyl phthalate (DBP) at various concentrations. Whole transcriptome analysis of adult Drosophila reveals that DBP exposure throughout development disrupts the expression of genes central to circadian rhythm regulation, including increased expression of vrille (vri, human NFIL3), timeless (tim, human TIMELESS) and period (per, human PER3), with decreased expression of Pigment-dispersing factor (Pdf). DBP exposure also alters the expression of the evolutionarily conserved nuclear receptor Hormone receptor-like in 38 (Hr38, human NR4A2), which is known to regulate Pdf expression. Furthermore, behavioral assays determined that exposing Drosophila to DBP throughout development modifies the circadian rhythm of adults. Although DBP inhibits the expression of signaling systems regulating vision, including Rh5 and Rh6, two light-sensing G-protein coupled receptors involved in the daily resetting of circadian rhythm, it does not influence eye development. Circadian rhythm genes are well conserved from flies to humans; therefore, we tested the effect of DBP exposure on human breast cells (MCF10A) and demonstrate that, similar to the fruit fly model, this exposure disrupts circadian rhythm (BMAL1 expression) at doses that promote the proliferation and migration ability of MCF10A cells. Our results are the first to provide comprehensive evidence that DBP interferes with circadian rhythm in both adult Drosophila and human cells, which may help to explain the broad physiological action of phthalates.

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  • 84.
    Liu, Wen
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Karolinska institutet.
    Mahdessian, Hovsep
    Helgadottir, Hafdis
    Zhou, Xingwu
    Thutkawkorapin, Jessada
    Jiao, Xiang
    Wolk, Alicja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Medical epidemiology. Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Lindblom, Annika
    Colorectal cancer risk susceptibility loci in a Swedish population2022In: Molecular Carcinogenesis, ISSN 0899-1987, E-ISSN 1098-2744, Vol. 61, no 3, p. 288-300Article in journal (Refereed)
    Abstract [en]

    To search for colorectal cancer (CRC) risk loci, Swedish samples were used for a genome-wide haplotype analysis. A logistic regression model was employed in 2663 CRC cases and 1642 controls in the discovery analysis. Three analyses were done, on all, familial-, and nonfamilial CRC samples and only results with odds ratio (OR) > 1 were analyzed. single nucleotide polymorphism (SNP) analysis did not generate any statistically significant results. Haplotype analysis suggested novel loci, on chromosome 2q36.1 (OR = 1.71, p value = 5.6924 × 10-8 ) in all CRC samples, chromosome 1q43 (OR = 4.04 p value = 3.24 × 10-8 ) in familial CRC samples, and two hits in nonfamilial CRC samples, chromosomes 2q36.1 (OR = 1.71 p value = 5.69 × 10-8 ) and 3p24.3 (OR = 1.62 p value = 6.21 × 10-9 ). Moreover, one locus on chromosome 20q13.33 was suggested in analyses of all samples, and five more novel loci were suggested on chromosomes 10q25.3, 15q,22.31, 17p11.2, 1p34.2, and 3q24. The haplotypes from the analysis of all samples were replicated in a second study of CRC cases and controls from the same part of Sweden. In summary, using haplotype analysis in Swedish CRC samples, the best hits were novel loci and the locus on chromosomes 2q36.1 and 20q13.33 suggested in the analysis of all samples were confirmed in a second cohort. The ORs were often higher than ORs from published genome-wide association study (GWAS). The study suggested it was possible that a risk locus could involve more than one gene, and that haplotypes could give information on the gene or genes possibly involved in the risk at specific locus.

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  • 85.
    Lukashina, Nina
    et al.
    JetBrains Res, Machine Learning Applicat & Deep Learning Grp, Kantemirovskaya Str 2, St Petersburg 197342, Russia..
    Williams, Michael J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Kartysheva, Elena
    JetBrains Res, Machine Learning Applicat & Deep Learning Grp, Kantemirovskaya Str 2, St Petersburg 197342, Russia.;ITMO Univ, Informat Technol & Programming Fac, Kronverksky Pr 49,Bldg A, St Petersburg 197101, Russia..
    Virko, Elizaveta
    JetBrains Res, Machine Learning Applicat & Deep Learning Grp, Kantemirovskaya Str 2, St Petersburg 197342, Russia.;HSE Univ, St Petersburg Sch Phys Math & Comp Sci, 16 Soyuza Pechatnikov St, St Petersburg 190121, Russia..
    Kudlak, Blazej
    Gdansk Univ Technol, Fac Chem, Dept Analyt Chem, 11-12 Narutowicza Str, PL-80233 Gdansk, Poland..
    Fredriksson, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Spjuth, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. IM Sechenov First Moscow State Med Univ, Inst Translat Med & Biotechnol, Trubetskay Str 8,Bldg 2, Moscow 119991, Russia..
    Integrating Statistical and Machine-Learning Approach for Meta-Analysis of Bisphenol A-Exposure Datasets Reveals Effects on Mouse Gene Expression within Pathways of Apoptosis and Cell Survival2021In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 22, no 19, article id 10785Article in journal (Refereed)
    Abstract [en]

    Bisphenols are important environmental pollutants that are extensively studied due to different detrimental effects, while the molecular mechanisms behind these effects are less well understood. Like other environmental pollutants, bisphenols are being tested in various experimental models, creating large expression datasets found in open access storage. The meta-analysis of such datasets is, however, very complicated for various reasons. Here, we developed an integrating statistical and machine-learning model approach for the meta-analysis of bisphenol A (BPA) exposure datasets from different mouse tissues. We constructed three joint datasets following three different strategies for dataset integration: in particular, using all common genes from the datasets, uncorrelated, and not co-expressed genes, respectively. By applying machine learning methods to these datasets, we identified genes whose expression was significantly affected in all of the BPA microanalysis data tested; those involved in the regulation of cell survival include: Tnfr2, Hgf-Met, Agtr1a, Bdkrb2; signaling through Mapk8 (Jnkl)); DNA repair (Hgf-Met, Mgmt); apoptosis (Tmbim6, Bcl2, Apaf1); and cellular junctions (F11r, Cldnd1, Ctnd1 and Yes1). Our results highlight the benefit of combining existing datasets for the integrated analysis of a specific topic when individual datasets are limited in size.

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  • 86.
    Lv, Yanling
    et al.
    Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Publ Hlth, Dept Nutr & Food Hyg,Hubei Key Lab Food Nutr & Saf, Wuhan, Peoples R China.;Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Publ Hlth, Minist Educ Key Lab Environm & Hlth, Wuhan, Peoples R China..
    Jiang, Guanhua
    Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Publ Hlth, Dept Nutr & Food Hyg,Hubei Key Lab Food Nutr & Saf, Wuhan, Peoples R China.;Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Publ Hlth, Minist Educ Key Lab Environm & Hlth, Wuhan, Peoples R China..
    Tan, Xiao
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Schiöth: Functional Pharmacology. Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Bao, Wei
    Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA..
    Chen, Liangkai
    Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Publ Hlth, Dept Nutr & Food Hyg,Hubei Key Lab Food Nutr & Saf, Wuhan, Peoples R China.;Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Publ Hlth, Minist Educ Key Lab Environm & Hlth, Wuhan, Peoples R China..
    Liu, Liegang
    Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Publ Hlth, Minist Educ Key Lab Environm & Hlth, Wuhan, Peoples R China..
    Association of Sleep Patterns and Lifestyles With Incident Hypertension: Evidence From a Large Population-Based Cohort Study2022In: Frontiers in Cardiovascular Medicine, E-ISSN 2297-055X, Vol. 9, article id 847452Article in journal (Refereed)
    Abstract [en]

    BackgroundAdherence to a healthy lifestyle (no smoking, consuming a healthy diet, engaging in physical activity, and maintaining a healthy weight) is recommended in current guidelines for hypertension prevention. However, evidence regarding the association between sleep behaviors, independently and jointly with traditional lifestyle factors, and the risk of hypertension is limited. MethodsThis prospective study included 165,493 participants who are free of hypertension at baseline from the UK Biobank. Sleep behaviors, including chronotype, sleep duration, insomnia, snoring, and daytime sleepiness were used to construct a healthy sleep score. We also derived a healthy lifestyle score based on smoking status, diet quality, physical activity, and body mass index (BMI). Cox proportional hazards regression models and competing risk analyses were used to estimate the associations of the healthy sleep score and healthy lifestyle score with the risk of hypertension. The population attributable risk percent (PAR%) was estimated for increased cases of hypertension due to poor adherence to a healthy sleep pattern or a healthy lifestyle. ResultsA total of 10,941 incident hypertension cases were documented during a median of 11.8 years of follow-up. The multivariable-adjusted hazard ratio (HR) for hypertension was 0.58 [95% confidence interval (CI): 0.52, 0.65] for participants with a sleep score of 5 compared with 0-1, and 0.48 (95% CI: 0.43, 0.54) for participants with a lifestyle score of 4 compared with those who scored 0. For joint association, those with a poor sleep pattern and a poor lifestyle had the highest risk of hypertension [HR: 2.41 (95% CI: 2.12, 2.74)]. PAR% was 14.7% (95% CI: 12.3%, 17.1%), 20.1% (95% CI: 17.6%, 22.6%), and 31.7% (95% CI: 27.6%, 35.6%) for poor adherence to a healthy sleep pattern, a healthy lifestyle, and the combination of a healthy sleep pattern and a healthy lifestyle. ConclusionBoth a healthy sleep pattern and a healthy lifestyle were associated with a lower risk of hypertension, and the benefits of adhering to a healthy sleep pattern complement the well-established lifestyle for the optimal primary prevention of hypertension. These findings support the current perspective that a healthy sleep pattern is an important part of a healthful and productive lifestyle for hypertension prevention.

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  • 87.
    Maretina, M. A.
    et al.
    DO Ott Res Inst Obstet Gynecol & Reproductol, St Petersburg 199034, Russia..
    Valetdinova, K. R.
    Russian Acad Sci, Fed Res Ctr, Siberian Branch, Inst Cytol & Genet, Novsibirsk 630090, Russia..
    Tsyganova, N. A.
    DO Ott Res Inst Obstet Gynecol & Reproductol, St Petersburg 199034, Russia..
    Egorova, A. A.
    DO Ott Res Inst Obstet Gynecol & Reproductol, St Petersburg 199034, Russia..
    Ovechkina, V. S.
    Russian Acad Sci, Fed Res Ctr, Siberian Branch, Inst Cytol & Genet, Novsibirsk 630090, Russia.;Novosibirsk State Univ, Novosibirsk 630090, Russia..
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Sechenov First Moscow State Med Univ, Moscow 119991, Russia..
    Zakian, S. M.
    Russian Acad Sci, Fed Res Ctr, Siberian Branch, Inst Cytol & Genet, Novsibirsk 630090, Russia.;Minist Healthcare Russian Federat, Meshalkin Natl Med Res Ctr, Novosibirsk 630055, Russia..
    Baranov, V. S.
    DO Ott Res Inst Obstet Gynecol & Reproductol, St Petersburg 199034, Russia..
    Kiselev, A. , V
    Identification of specific gene methylation patterns during motor neuron differentiation from spinal muscular atrophy patient-derived iPSC2022In: Gene, ISSN 0378-1119, E-ISSN 1879-0038, Vol. 811, article id 146109Article in journal (Refereed)
    Abstract [en]

    Spinal muscular atrophy is a progressive motor neuron disorder caused by deletions or point mutations in the SMN1 gene. It is not known why motor neurons are particularly sensitive to a decrease in SMN protein levels and what factors besides SMN2 underlie the high clinical heterogeneity of the disease. Here we studied the methylation patterns of genes on sequential stages of motor neuron differentiation from induced pluripotent stem cells derived from the patients with SMA type I and II. The genes involved in the regulation of pluripotency, neural differentiation as well as those associated with spinal muscular atrophy development were included. The results show that the PAX6, HB9, CHAT, ARHGAP22, and SMN2 genes are differently methylated in cells derived from SMA patients compared to the cells of healthy individuals. This study clarifies the specificities of the disease pathogenesis and extends the knowledge of pathways involved in the SMA progression.

  • 88.
    Martikainen, Teemu
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Sigurdardottir, Fjola
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Schiöth: Functional Pharmacology.
    Omland, Torbjørn
    Cedernaes, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Effects of curtailed sleep on cardiac stress biomarkers following high-intensity exercise.2022In: Molecular metabolism, ISSN 2212-8778, Vol. 58, article id 101445Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Physical exercise - especially at high intensity - is known to impose cardiac stress, as mirrored by, e.g., increased blood levels of cardiac stress biomarkers, such as cardiac Troponin T (cTnT) and NT-proBNP. Here, we examined in healthy young participants whether a few nights of short sleep duration alters the effects of acute exercise on these blood biomarkers.

    METHODS: Sixteen men participated in a randomized order in a crossover design, comprising three consecutive nights of a) normal sleep duration (NS, 8.5 hours of sleep/night) and b) sleep restriction (SR, 4.25 hours of sleep/night). Blood was repeatedly sampled for determination of NT-proBNP and cTnT serum levels before and after a high-intensity exercise protocol (i.e., 75% VO2maxReserve cycling on an ergometer).

    RESULTS: Under pre-exercise sedentary conditions, blood levels of cTnT and NT-proBNP did not significantly differ between the sleep conditions (P>0.10). However, in response to exercise, the surge of circulating cTnT was significantly greater following SR than NS (+37-38% at 120-240 min post-exercise, P≤0.05). While blood levels of NT-proBNP rose significantly in response to exercise, they did not differ between the sleep conditions.

    CONCLUSION: Recurrent sleep restriction may increase the cardiac stress response to acute high-intensity exercise in healthy young individuals. However, our findings must be confirmed in for example older subjects or in patients with a history of heart disease.

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  • 89. Merikanto, Ilona
    et al.
    Kortesoja, Laura
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Chung, Frances
    Cedernaes, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine.
    Espie, Colin A
    Morin, Charles M
    Dauvilliers, Yves
    Partinen, Markku
    De Gennaro, Luigi
    Wing, Yun Kwok
    Chan, Ngan Yin
    Inoue, Yuichi
    Matsui, Kentaro
    Holzinger, Brigitte
    Plazzi, Giuseppe
    Mota-Rolim, Sérgio Arthuro
    Leger, Damien
    Penzel, Thomas
    Bjorvatn, Bjørn
    Evening-types show highest increase of sleep and mental health problems during the COVID-19 pandemic - Multinational study on 19,267 adults.2021In: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 45, no 2, article id zsab216Article in journal (Refereed)
    Abstract [en]

    STUDY OBJECTIVES: Individual circadian type is a ubiquitous trait defining sleep, with eveningness often associated with poorer sleep and mental health than morningness. However, it is unknown whether COVID-19 pandemic has differentially affected sleep and mental health depending on the circadian type. Here, the differences in sleep and mental health between circadian types are examined globally before and during the COVID-19 pandemic.

    METHODS: The sample collected between May and August 2020 across 12 countries/regions consisted of 19,267 adults with information on their circadian type. Statistical analyses were performed by using Complex Sample procedures, stratified by country and weighted by the number of inhabitants in the country/area of interest and by the relative number of responders in that country/area.

    RESULTS: Evening-types had poorer mental health, well-being, and quality of life or health than other circadian types during the pandemic. Sleep-wake schedules were delayed especially on working days, and evening-types reported an increase in sleep duration. Sleep problems increased in all circadian types, but especially among evening-types, moderated by financial suffering and confinement. Intermediate-types were less vulnerable to sleep changes, although morningness protected from most sleep problems. These findings were confirmed after adjusting for age, sex, duration of the confinement or socio-economic status during the pandemic.

    CONCLUSIONS: These findings indicate an alarming increase in sleep and mental health problems, especially among evening-types as compared to other circadian types during the pandemic.

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  • 90.
    Meth, Elisa M. S.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    van Egmond, Lieve T.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Sleep duration regularity as a predictor of the cardiovascular response to acute exercise2021In: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 44, no 8, article id zsab115Article in journal (Other academic)
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  • 91.
    Miguet, Maud
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Rukh, Gull
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Titova, Olga E
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Medical epidemiology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Sechenov First Moscow State Med Univ, Inst Translat Med & Biotechnol, Moscow 119991, Russia..
    Important Difference between Occupational Hazard Exposure among Shift Workers and Other Workers; Comparing Workplace before and after 19802020In: International Journal of Environmental Research and Public Health, ISSN 1661-7827, E-ISSN 1660-4601, Vol. 17, no 20, article id 7495Article in journal (Refereed)
    Abstract [en]

    Improving health and safety at work has been an important issue for the European Union since the 1980s. The existing literature supports that shift work is associated with multiple indicators of poor health but frequently neglects the potential impact of occupational hazards. This study aims at describing and comparing the exposure to different workplace hazards among shift and other workers before and after 1980. Exposure to different workplace hazards (noise, dust, pollutant, and other physical stressors) were analyzed among 119,413 participants from the UK Biobank cohort. After stratifying the analyses before and after 1980, exposure was compared between shift and other workers. Potential confounding variables (sex, age, ethnicity, education level, occupational category, and neuroticism) were adjusted for in the log-binomial regression. Shift workers had a higher prevalence ratio (PR) than other workers of being exposed to almost all identified hazards both before or after 1980. They were also more likely to be exposed to multiple hazards compared to other workers, both before 1980 (PR: 1.25; 95% CI: 1.21-1.30) and after 1980 (PR: 1.34; 95% CI: 1.30-1.38). The prevalence of all measured risk factors was higher after 1980 than before 1980 among shift workers. Of note, the work environment has improved overall for other workers. Our findings suggest that changes at the workplace have benefited other workers more than shift workers as they are still more exposed to all occupational hazards.

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  • 92.
    Miguet, Maud
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Venetis, Sotirios
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Rukh, Gull
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Sechenov First Moscow State Med Univ, Inst Translat Med & Biotechnol, Moscow, Russia.
    Time spent outdoors and risk of myocardial infarction and stroke in middle and old aged adults: Results from the UK Biobank prospective cohort2021In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 199, article id 111350Article in journal (Refereed)
    Abstract [en]

    Background

    Time spent outdoors has been previously related to several cardiovascular risk factors, implying that it may confer either beneficial or harmful effects on cardiovascular health. However, no large population-based studies have examined the relation between time spent outdoors and myocardial infarction and stroke.

    Objectives

    We aimed to investigate the longitudinal relation between time spent outdoors and myocardial infarction and stroke in large UK population‐based cohort.

    Methods

    A total of 446,648 participants from UK Biobank were included in the study of which 431,146 participants (56% females and 44% males with a mean age of 56.4 ± 8.1 years) were followed for a median time of 7 years. Time spent outdoors was self-reported and participants were stratified into quantiles (less than 1.5 [reference group]; 1.5 to 2.4; 2.5 to 3.5 and more than 3.5 h per day outdoors). Myocardial infarction and stroke events were either collected from hospital records and death registries or were self-reported by the participants. Cox proportional hazard regression was used for the analysis. In addition to age and sex, analyses were adjusted for potential demographic (TDI, ethnic background, current employment status), lifestyle (alcohol intake frequency, current tobacco use, sedentary time and moderate-to-vigorous physical activity), health related factors (BMI, systolic and diastolic blood pressure) and environmental indicators (NO2, NOx, PM10, PM2.5-10, PM2,5, noise pollution, % greenspace, % natural environment and % water).

    Results

    A 20% increased risk for myocardial infarction incidence was observed among participants who reported spending more than 3.5 h/day outdoors (HR: 1.20, 95% CI: 1.06–1.36) compared to the reference group. A trend was also observed for stroke (HR: 1.14, 95% CI: 0.97–1.34).

    Conclusion

    Findings from the present study indicate that spending more than 3.5 h/day outdoors is a risk factor for myocardial infarction and stroke. Future research is needed to further understand the relation between time spent outdoors and cardiovascular disease.

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  • 93.
    Mohamed, Mohamed S.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Schiöth: Functional Pharmacology.
    Johansson, Anton
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Schiöth: Functional Pharmacology.
    Jonsson, Jörgen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Schiöth: Functional Pharmacology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Schiöth: Functional Pharmacology.
    Dissecting the Molecular Mechanisms Surrounding Post-COVID-19 Syndrome and Neurological Features2022In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 23, no 8, article id 4275Article, review/survey (Refereed)
    Abstract [en]

    Many of the survivors of the novel coronavirus disease (COVID-19) are suffering from persistent symptoms, causing significant morbidity and decreasing their quality of life, termed "post-COVID-19 syndrome" or "long COVID". Understanding the mechanisms surrounding PCS is vital to developing the diagnosis, biomarkers, and possible treatments. Here, we describe the prevalence and manifestations of PCS, and similarities with previous SARS epidemics. Furthermore, we look at the molecular mechanisms behind the neurological features of PCS, where we highlight important neural mechanisms that may potentially be involved and pharmacologically targeted, such as glutamate reuptake in astrocytes, the role of NMDA receptors and transporters (EAAT2), ROS signaling, astrogliosis triggered by NF-kappa B signaling, KNDy neurons, and hypothalamic networks involving Kiss1 (a ligand for the G-protein-coupled receptor 54 (GPR54)), among others. We highlight the possible role of reactive gliosis following SARS-CoV-2 CNS injury, as well as the potential role of the hypothalamus network in PCS manifestations.

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  • 94.
    Mohamed, Mohamed S.
    et al.
    Uppsala Univ, Dept Neurosci, Funct Pharmacol Unit, Uppsala, Sweden..
    Moulin, Thiago
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Sechenov First Moscow State Med Univ, Inst Translat Med & Biotechnol, Moscow, Russia..
    Sex differences in COVID-19: the role of androgens in disease severity and progression2021In: Endocrine, ISSN 1355-008X, E-ISSN 1559-0100, Vol. 71, no 1, p. 3-8Article, review/survey (Refereed)
    Abstract [en]

    Purpose Throughout the SARS-CoV2 pandemic, multiple reports show higher percentages of hospitalization, morbidity, and mortality among men than women, indicating that men are more affected by COVID-19. The pathophysiology of this difference is yet not established, but recent studies suggest that sex hormones may influence the viral infectivity process. Here, we review the current evidence of androgen sensitivity as a decisive factor for COVID-19 disease severity. Methods Relevant literature investigating the role of androgens in COVID-19 was assessed. Further, we describe several drugs suggested as beneficial for COVID-19 treatment related to androgen pathways. Lastly, we looked at androgen sensitivity as a predictor for COVID-19 progression and ongoing clinical trials on androgen suppression therapies as a line of treatment. Results SARS-COV2 virus spike proteins utilize Transmembrane protease serine 2 (TMPRSS2) for host entry. Androgen receptors are transcription promoters for TMPRSS2 and can, therefore, facilitate SARS-COV2 entry. Variants in the androgen receptor gene correlate with androgen sensitivity and are implicated in diseases like androgenetic alopecia and prostate cancer, conditions that have been associated with worse COVID-19 outcomes and hospitalization. Conclusion Androgen's TMPRSS2-mediated actions might explain both the low fatalities observed in prepubertal children and the differences between sexes regarding SARS-COV2 infection. Androgen sensitivity may be a critical factor in determining COVID-19 disease severity, and sensitivity tests can, therefore, help in predicting patient outcomes.

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  • 95. Morin, Charles M.
    et al.
    Bjorvatn, Bjørn
    Chung, Frances
    Holzinger, Brigitte
    Partinen, Markku
    Penzel, Thomas
    Ivers, Hans
    Wing, Yun Kwok
    Chan, Ngan Yin
    Merikanto, Ilona
    Mota-Rolim, Sergio
    Macêdo, Tainá
    De Gennaro, Luigi
    Léger, Damien
    Dauvilliers, Yves
    Plazzi, Giuseppe
    Nadorff, Michael R.
    Bolstad, Courtney J.
    Sieminski, Mariusz
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Cedernaes, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine.
    Inoue, Yuchi
    Han, Fang
    Espie, Colin A.
    Insomnia, anxiety, and depression during the COVID-19 pandemic: an international collaborative study2021In: Sleep Medicine, ISSN 1389-9457, E-ISSN 1878-5506, Vol. 87, p. 38-45Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE AND STUDY OBJECTIVE: The COVID-19 pandemic has produced unprecedented changes in social, work, and leisure activities, which all have had major impact on sleep and psychological well-being. This study documented the prevalence of clinical cases of insomnia, anxiety, and depression and selected risk factors (COVID-19, confinement, financial burden, social isolation) during the first wave of the pandemic in 13 countries throughout the world.

    DESIGN AND PARTICIPANTS: International, multi-center, harmonized survey of 22 330 adults (mean age = 41.9 years old, range 18-95; 65.6% women) from the general population in 13 countries and four continents. Participants were invited to complete a standardized web-based survey about sleep and psychological symptoms during the first wave of the COVID-19 pandemic from May to August 2020.

    RESULTS: Clinical insomnia symptoms were reported by 36.7% (95% CI, 36.0-37.4) of respondents and 17.4% (95% CI, 16.9-17.9) met criteria for a probable insomnia disorder. There were 25.6% (95% CI, 25.0-26.2) with probable anxiety and 23.1% (95% CI, 22.5-23.6) with probable depression. Rates of insomnia symptoms (>40%) and insomnia disorder (>25%) were significantly higher in women, younger age groups, and in residents of Brazil, Canada, Norway, Poland, USA, and United Kingdom compared to residents from Asian countries (China and Japan, 8% for disorder and 22%-25% for symptoms) (all Ps < 0.01). Proportions of insomnia cases were significantly higher among participants who completed the survey earlier in the first wave of the pandemic relative to those who completed it later. Risks of insomnia were higher among participants who reported having had COVID-19, who reported greater financial burden, were in confinement for a period of four to five weeks, and living alone or with more than five people in same household. These associations remained significant after controlling for age, sex, and psychological symptoms.

    CONCLUSION AND RELEVANCE: Insomnia, anxiety, and depression were very prevalent during the first wave of the COVID-19 pandemic. Public health prevention programs are needed to prevent chronicity and reduce long-term adverse outcomes associated with chronic insomnia and mental health problems.

  • 96.
    Moulin, Thiago
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Univ Fed Rio de Janeiro, Inst Med Biochem Leopoldo de Meis, Rio De Janeiro, Brazil..
    Mental Health in Academia: The Role of Workplace Relationships2020In: Frontiers in Psychology, E-ISSN 1664-1078, Vol. 11, article id 562457Article in journal (Refereed)
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  • 97.
    Moulin, Thiago
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Univ Fed Rio de Janeiro, Inst Med Biochem Leopoldo de Meis, Rio De Janeiro, Brazil.;Uppsala Univ, Dept Neurosci, Uppsala, Sweden..
    Amaral, Olavo B.
    Univ Fed Rio de Janeiro, Inst Med Biochem Leopoldo de Meis, Rio De Janeiro, Brazil..
    Using collaboration networks to identify authorship dependence in meta-analysis results2020In: Research Synthesis Methods, ISSN 1759-2879, E-ISSN 1759-2887, Vol. 11, no 5, p. 655-668Article in journal (Refereed)
    Abstract [en]

    Meta-analytic methods are powerful resources to summarize the existing evidence concerning a given research question and are widely used in many academic fields. Meta-analyzes can also be used to study sources of heterogeneity and bias among results, which should be considered to avoid inaccuracies. Many of these sources can be related to study authorship, as both methodological heterogeneity and researcher bias may lead to deviations in results between different research groups. In this work, we describe a method to objectively attribute study authorship within a given meta-analysis to different research groups by using graph cluster analysis of collaboration networks. We then provide empirical examples of how the research group of origin can impact effect size in distinct types of meta-analyzes, demonstrating how non-independence between within-group results can bias effect size estimates if uncorrected. Finally, we show that multilevel random-effects models using research group as a level of analysis can be a simple tool for correcting for authorship dependence in results.

  • 98.
    Moulin, Thiago C.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Leopoldo de Meis Institute of Medical Biochemistry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; Brain Institute, Federal University of Rio Grande do Norte, Rio Grande do Norte, Brazil.
    Petiz, Lyvia L.
    Brain Institute, Federal University of Rio Grande do Norte, Rio Grande do Norte, Brazil.
    Rayêe, Danielle
    Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
    Winne, Jessica
    Brain Institute, Federal University of Rio Grande do Norte, Rio Grande do Norte, Brazil.
    Maia, Roberto G.
    Leopoldo de Meis Institute of Medical Biochemistry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
    Lima da Cruz, Rafael V.
    Brain Institute, Federal University of Rio Grande do Norte, Rio Grande do Norte, Brazil.
    Amaral, Olavo B.
    Leopoldo de Meis Institute of Medical Biochemistry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazi.
    Leão, Richardson N.
    Brain Institute, Federal University of Rio Grande do Norte, Rio Grande do Norte, Brazil.
    Chronic in vivo optogenetic stimulation modulates neuronal excitability, spine morphology, and Hebbian plasticity in the mouse hippocampus2019In: Hippocampus, ISSN 1050-9631, E-ISSN 1098-1063, Vol. 29, no 8, p. 755-761Article in journal (Refereed)
    Abstract [en]

    Prolonged increases in excitation can trigger cell‐wide homeostatic responses in neurons, altering membrane channels, promoting morphological changes, and ultimately reducing synaptic weights. However, how synaptic downscaling interacts with classical forms of Hebbian plasticity is still unclear. In this study, we investigated whether chronic optogenetic stimulation of hippocampus CA1 pyramidal neurons in freely moving mice could (a) cause morphological changes reminiscent of homeostatic scaling, (b) modulate synaptic currents that might compensate for chronic excitation, and (c) lead to alterations in Hebbian plasticity. After 24 hr of stimulation with 15‐ms blue light pulses every 90 s, dendritic spine density and area were reduced in the CA1 region of mice expressing channelrhodopsin‐2 (ChR2) when compared to controls. This protocol also reduced the amplitude of mEPSCs for both the AMPA and NMDA components in ex vivo slices obtained from ChR2‐expressing mice immediately after the end of stimulation. Finally, chronic stimulation impaired the induction of LTP and facilitated that of LTD in these slices. Our results indicate that neuronal responses to prolonged network excitation can modulate subsequent Hebbian plasticity in the hippocampus.

  • 99.
    Moulin, Thiago
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Covill, Laura E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Karolinska Inst, Ctr Hematol & Regenerat Med, Stockholm, Sweden..
    Itskov, Pavel M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Sechenov First Moscow State Med Univ, Inst Pharm, Dept Pharmacol, Moscow, Russia.;Champalimaud Ctr Unknown, Lisbon, Portugal..
    Williams, Michael J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Sechenov First Moscow State Med Univ, Inst Translat Med & Biotechnol, Moscow, Russia..
    Rodent and fly models in behavioral neuroscience: An evaluation of methodological advances, comparative research, and future perspectives2021In: Neuroscience and Biobehavioral Reviews, ISSN 0149-7634, E-ISSN 1873-7528, Vol. 120, p. 1-12Article, review/survey (Refereed)
    Abstract [en]

    The assessment of behavioral outcomes is a central component of neuroscientific research, which has required continuous technological innovations to produce more detailed and reliable findings. In this article, we provide an in-depth review on the progress and future implications for three model organisms (mouse, rat, and Drosophila) essential to our current understanding of behavior. By compiling a comprehensive catalog of popular assays, we are able to compare the diversity of tasks and usage of these animal models in behavioral research. This compilation also allows for the evaluation of existing state-of-the-art methods and experimental applications, including optogenetics, machine learning, and high-throughput behavioral assays. We go on to discuss novel apparatuses and inter-species analyses for centrophobism, feeding behavior, aggression and mating paradigms, with the goal of providing a unique view on comparative behavioral research. The challenges and recent advances are evaluated in terms of their translational value, ethical procedures, and trustworthiness for behavioral research.

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    fulltext
  • 100.
    Moulin, Thiago
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Ferro, Federico
    Uppsala Univ, Dept Neurosci, Funct Pharmacol Unit, S-75124 Uppsala, Sweden..
    Berkins, Samuel
    Uppsala Univ, Dept Neurosci, Funct Pharmacol Unit, S-75124 Uppsala, Sweden..
    Hoyer, Angela
    Uppsala Univ, Dept Neurosci, Funct Pharmacol Unit, S-75124 Uppsala, Sweden..
    Williams, Michael J.
    Uppsala Univ, Dept Neurosci, Funct Pharmacol Unit, S-75124 Uppsala, Sweden..
    Schioth, Helgi B.
    Uppsala Univ, Dept Neurosci, Funct Pharmacol Unit, S-75124 Uppsala, Sweden.;Sechenov First Moscow State Med Univ, Inst Translat Med & Biotechnol, Moscow 119146, Russia..
    Transient Administration of Dopaminergic Precursor Causes Inheritable Overfeeding Behavior in Young Drosophila melanogaster Adults2020In: Brain Sciences, ISSN 2076-3425, E-ISSN 2076-3425, Vol. 10, no 8, article id 487Article in journal (Refereed)
    Abstract [en]

    Imbalances in dopaminergic signaling during development have been indicated as part of the underlying neurobiology of several psychiatric illnesses, including schizophrenia, major depression, bipolar disorder, and food addiction. Yet, how transient manipulation of dopaminergic signaling influences long-lasting behavioral consequences, or if these modifications can induce inheritable traits, it is still not understood. In this study, we used theDrosophila melanogastermodel to test if transient pharmacological activation of the dopaminergic system leads to modulations of feeding and locomotion in adult flies. We observed that transient administration of a dopaminergic precursor, levodopa, at 6 h, 3 days or 5 days post-eclosion, induced overfeeding behavior, while we did not find significant effects on locomotion. Moreover, this phenotype was inherited by the offspring of flies treated 6 h or 3 days post-eclosion, but not the offspring of those treated 5 days post-eclosion. These results indicate that transient alterations in dopaminergic signaling can produce behavioral alterations in adults, which can then be carried to descendants. These findings provide novel insights into the conditions in which environmental factors can produce transgenerational eating disorders.

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    FULLTEXT01
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