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  • 1.
    Aare, Sudhakar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Ochala, Julien
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Norman, Holly S
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Radell, Peter
    Eriksson, Lars I
    Göransson, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Chen, Yi-Wen
    Hoffman, Eric P
    Larsson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Mechanisms underlying the sparing of masticatory versus limb muscle function in an experimental critical illness model2011In: Physiological Genomics, ISSN 1094-8341, E-ISSN 1531-2267, Vol. 43, no 24, 1334-1350 p.Article in journal (Refereed)
    Abstract [en]

    Acute quadriplegic myopathy (AQM) is a common debilitating acquired disorder in critically ill intensive care unit (ICU) patients which is characterized by tetraplegia/generalized weakness of limb and trunk muscles. Masticatory muscles, on the other hand, are typically spared or less affected, yet the mechanisms underlying this striking muscle-specific difference remain unknown. This study aims to evaluate physiological parameters and the gene expression profiles of masticatory and limb muscles exposed to factors suggested to trigger AQM, such as mechanical ventilation, immobilization, neuromuscular blocking agents (NMBA), corticosteroids (CS) and sepsis for five days by using a unique porcine model mimicking the ICU conditions. Single muscle fiber cross-sectional area and force-generating capacity, i.e., maximum force normalized to fiber cross-sectional area (specific force), revealed maintained masseter single muscle fiber cross-sectional area and specific-force after five days exposure to all triggering factors. This is in sharp contrast to observations in limb and trunk muscles, showing a dramatic decline in specific force in response to five days exposure to the triggering factors. Significant differences in gene expression were observed between craniofacial and limb muscles, indicating a highly complex and muscle specific response involving transcription and growth factors, heat shock proteins, matrix metalloproteinase inhibitor, oxidative stress responsive elements and sarcomeric proteins underlying the relative sparing of cranial versus spinal nerve innervated muscles during exposure to the ICU intervention.

  • 2.
    Abdul-Hussein, Saba
    et al.
    Department of Pathology, University of Gothenburg, Gothenburg, Sweden.
    Rahl, Karin
    Department of Pathology, University of Gothenburg, Gothenburg, Sweden.
    Moslemi, Ali-Reza
    Department of Pathology, University of Gothenburg, Gothenburg, Sweden.
    Tajsharghi, Homa
    Department of Pathology, University of Gothenburg, Gothenburg, Sweden / Department of Clinical and Medical Genetics, University of Gothenburg, Gothenburg, Sweden.
    Phenotypes of myopathy-related beta-tropomyosin mutants in human and mouse tissue cultures2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 9, e72396Article in journal (Refereed)
    Abstract [en]

    Mutations in TPM2 result in a variety of myopathies characterised by variable clinical and morphological features. We used human and mouse cultured cells to study the effects of β-TM mutants. The mutants induced a range of phenotypes in human myoblasts, which generally changed upon differentiation to myotubes. Human myotubes transfected with the E41K-β-TM(EGFP) mutant showed perinuclear aggregates. The G53ins-β-TM(EGFP) mutant tended to accumulate in myoblasts but was incorporated into filamentous structures of myotubes. The K49del-β-TM(EGFP) and E122K-β-TM(EGFP) mutants induced the formation of rod-like structures in human cells. The N202K-β-TM(EGFP) mutant failed to integrate into thin filaments and formed accumulations in myotubes. The accumulation of mutant β-TM(EGFP) in the perinuclear and peripheral areas of the cells was the striking feature in C2C12. We demonstrated that human tissue culture is a suitable system for studying the early stages of altered myofibrilogenesis and morphological changes linked to myopathy-related β-TM mutants. In addition, the histopathological phenotype associated with expression of the various mutant proteins depends on the cell type and varies with the maturation of the muscle cell. Further, the phenotype is a combinatorial effect of the specific amino acid change and the temporal expression of the mutant protein.

  • 3.
    Abdul-Hussein, Saba
    et al.
    Department of Pathology, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
    van der Ven, Peter F. M.
    Department of Molecular Cell Biology, Institute for Cell Biology, University of Bonn, Bonn, Germany.
    Tajsharghi, Homa
    Department of Pathology, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden / Department of Clinical and Medical Genetics, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Expression profiles of muscle disease-associated genes and their isoforms during differentiation of cultured human skeletal muscle cells2012In: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 13, 262Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The formation of contractile myofibrils requires the stepwise onset of expression of muscle specific proteins. It is likely that elucidation of the expression patterns of muscle-specific sarcomeric proteins is important to understand muscle disorders originating from defects in contractile sarcomeric proteins.

    METHODS: We investigated the expression profile of a panel of sarcomeric components with a focus on proteins associated with a group of congenital disorders. The analyses were performed in cultured human skeletal muscle cells during myoblast proliferation and myotube development.

    RESULTS: Our culture technique resulted in the development of striated myotubes and the expression of adult isoforms of the sarcomeric proteins, such as fast TnI, fast TnT, adult fast and slow MyHC isoforms and predominantly skeletal muscle rather than cardiac actin. Many proteins involved in muscle diseases, such as beta tropomyosin, slow TnI, slow MyBPC and cardiac TnI were readily detected in the initial stages of muscle cell differentiation, suggesting the possibility of an early role for these proteins as constituent of the developing contractile apparatus during myofibrillogenesis. This suggests that in disease conditions the mechanisms of pathogenesis for each of the mutated sarcomeric proteins might be reflected by altered expression patterns, and disturbed assembly of cytoskeletal, myofibrillar structures and muscle development.

    CONCLUSIONS: In conclusion, we here confirm that cell cultures of human skeletal muscle are an appropriate tool to study developmental stages of myofibrillogenesis. The expression of several disease-associated proteins indicates that they might be a useful model system for studying the pathogenesis of muscle diseases caused by defects in specific sarcomeric constituents.

  • 4. Abel, Olubunmi
    et al.
    Powell, John F
    Andersen, Peter M
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Al-Chalabi, Ammar
    Credibility analysis of putative disease-causing genes using bioinformatics2013In: PLoS ONE, ISSN 1932-6203, Vol. 8, no 6, e64899- p.Article in journal (Refereed)
    Abstract [en]

    Background: Genetic studies are challenging in many complex diseases, particularly those with limited diagnostic certainty, low prevalence or of old age. The result is that genes may be reported as disease-causing with varying levels of evidence, and in some cases, the data may be so limited as to be indistinguishable from chance findings. When there are large numbers of such genes, an objective method for ranking the evidence is useful. Using the neurodegenerative and complex disease amyotrophic lateral sclerosis (ALS) as a model, and the disease-specific database ALSoD, the objective is to develop a method using publicly available data to generate a credibility score for putative disease-causing genes.

    Methods: Genes with at least one publication suggesting involvement in adult onset familial ALS were collated following an exhaustive literature search. SQL was used to generate a score by extracting information from the publications and combined with a pathogenicity analysis using bioinformatics tools. The resulting score allowed us to rank genes in order of credibility. To validate the method, we compared the objective ranking with a rank generated by ALS genetics experts. Spearman's Rho was used to compare rankings generated by the different methods.

    Results: The automated method ranked ALS genes in the following order: SOD1, TARDBP, FUS, ANG, SPG11, NEFH, OPTN, ALS2, SETX, FIG4, VAPB, DCTN1, TAF15, VCP, DAO. This compared very well to the ranking of ALS genetics experts, with Spearman's Rho of 0.69 (P = 0.009).

    Conclusion: We have presented an automated method for scoring the level of evidence for a gene being disease-causing. In developing the method we have used the model disease ALS, but it could equally be applied to any disease in which there is genotypic uncertainty.

  • 5. Abosch, Aviva
    et al.
    Timmermann, Lars
    Bartley, Sylvia
    Rietkerk, Hans Guido
    Whiting, Donald
    Connolly, Patrick J.
    Lanctin, David
    Hariz, Marwan I.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    An International Survey of Deep Brain Stimulation Procedural Steps2013In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 91, no 1, 1-11 p.Article, review/survey (Refereed)
    Abstract [en]

    Background: Deep brain stimulation (DBS) surgery is standard of care for the treatment of certain movement disorders.

    Objective: We sought to characterize the spectrum of steps performed in DBS surgery, at centers around the world where this surgery is performed.

    Methods: We identified the main steps in DBS surgery workflow and grouped these 19 steps into 3 phases (preoperative, operative, and postoperative). A survey tool, informed by a pilot survey, was administered internationally by trained study personnel at high- and low-volume DBS centers. Procedural components, duration, and surgeon motivational factors were assessed. Cluster analysis was used to identify procedural and behavioral clusters.

    Results: One hundred eighty-five procedure workflow surveys (143 DBS centers) and 65 online surveys of surgeon motivational drivers were completed (45% response rate). Significant heterogeneity in technique, operative time, and surgeon motivational drivers was reported across centers.

    Conclusions: We provide a description of the procedural steps involved in DBS surgery and the duration of these steps, based on an international survey. These data will enable individual surgeons and centers to examine their own experience relative to colleagues at other centers and in other countries. Such information could also be useful in comparing efficiencies and identifying workflow obstacles between different hospital environments.

  • 6.
    Abu Hamdeh, Sami
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Marklund, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lannsjö, Marianne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Rehabilitation Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Howells, Tim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Extended anatomical grading in diffuse axonal injury using MRI: Hemorrhagic lesions in the substantia nigra and mesencephalic tegmentum indicate poor long-term outcome2017In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 5, no 34, 341-352 p.Article in journal (Refereed)
    Abstract [en]

    Clinical outcome after traumatic diffuse axonal injury (DAI) is difficult to predict. In this study, three magnetic resonance imaging (MRI) sequences were used to quantify the anatomical distribution of lesions, to grade DAI according to the Adams grading system, and to evaluate the value of lesion localization in combination with clinical prognostic factors to improve outcome prediction. Thirty patients (mean 31.2 years ±14.3 standard deviation) with severe DAI (Glasgow Motor Score [GMS] <6) examined with MRI within 1 week post-injury were included. Diffusion-weighted (DW), T2*-weighted gradient echo and susceptibility-weighted (SWI) sequences were used. Extended Glasgow outcome score was assessed after 6 months. Number of DW lesions in the thalamus, basal ganglia, and internal capsule and number of SWI lesions in the mesencephalon correlated significantly with outcome in univariate analysis. Age, GMS at admission, GMS at discharge, and low proportion of good monitoring time with cerebral perfusion pressure <60 mm Hg correlated significantly with outcome in univariate analysis. Multivariate analysis revealed an independent relation with poor outcome for age (p = 0.005) and lesions in the mesencephalic region corresponding to substantia nigra and tegmentum on SWI (p  = 0.008). We conclude that higher age and lesions in substantia nigra and mesencephalic tegmentum indicate poor long-term outcome in DAI. We propose an extended MRI classification system based on four stages (stage I—hemispheric lesions, stage II—corpus callosum lesions, stage III—brainstem lesions, and stage IV—substantia nigra or mesencephalic tegmentum lesions); all are subdivided by age (≥/<30 years).

  • 7.
    Adair, Brooke
    et al.
    School of Allied Health, Australian Catholic University, Fitzroy, Vic., Australia.
    Ullenhag, Anna
    Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden.
    Keen, Deb
    Autism Centre of Excellence, Griffith University, Mt Gravatt, Qld, Australia.
    Granlund, Mats
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Behavioural Science and Social Work. Jönköping University, School of Education and Communication, HLK, CHILD. Jönköping University, School of Health and Welfare, HHJ. CHILD.
    Imms, Christine
    School of Allied Health, Australian Catholic University, Fitzroy, Vic., Australia.
    The effect of interventions aimed at improving participation outcomes for children with disabilities: a systematic review2015In: Developmental Medicine & Child Neurology, ISSN 0012-1622, E-ISSN 1469-8749, Vol. 57, no 12, 1093-1104 p.Article, review/survey (Refereed)
    Abstract [en]

    Aim

    Enhancement of participation has been described as the ultimate outcome for health and educational interventions. The goal of this systematic review was to identify and critically appraise studies that aimed to improve the participation outcomes of children with disabilities.

    Method

    Nine databases that index literature from the fields of health, psychology, and education were searched to retrieve information on research conducted with children with disabilities aged between 5 years and 18 years. Articles were included if the author(s) reported that participation was an intended outcome of the intervention. The articles included were limited to those reporting high-level primary research, as defined by Australia's National Health and Medical Research Council evidence hierarchy guidelines. No restrictions were placed on the type of intervention being investigated.

    Results

    Seven randomized controlled or pseudo-randomized studies were included. Only three of these studies identified participation as a primary outcome. Both individualized and group-based approaches to enhancing participation outcomes appeared to be effective. Studies of interventions with a primary focus on body function or activity level outcomes did not demonstrate an effect on participation outcomes.

    Intepretation

    Few intervention studies have focused on participation as a primary outcome measure. Approaches using individually tailored education and mentoring programmes were found to enhance participation outcomes, while exercise programmes, where participation was a secondary outcome, generally demonstrated little effect.

  • 8.
    Adamczuk, Katarzyna
    et al.
    Katholieke Univ Leuven, Lab Cognit Neurol, B-3000 Louvain, Belgium.;Katholieke Univ Leuven, Leuven Inst Neurosci & Dis, Alzheimer Res Ctr, B-3000 Louvain, Belgium..
    Schaeverbeke, Jolien
    Katholieke Univ Leuven, Lab Cognit Neurol, B-3000 Louvain, Belgium.;Katholieke Univ Leuven, Leuven Inst Neurosci & Dis, Alzheimer Res Ctr, B-3000 Louvain, Belgium..
    Vanderstichele, Hugo M. J.
    ADx NeuroSci, B-9052 Ghent, Belgium..
    Lilja, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. GE Healthcare, S-75125 Uppsala, Sweden..
    Nelissen, Natalie
    Katholieke Univ Leuven, Lab Cognit Neurol, B-3000 Louvain, Belgium.;Univ Oxford, Dept Psychiat, Oxford OX3 7JX, England..
    Van Laere, Koen
    Katholieke Univ Leuven, Leuven Inst Neurosci & Dis, Alzheimer Res Ctr, B-3000 Louvain, Belgium.;Katholieke Univ Leuven, Nucl Med & Mol Imaging Dept, B-3000 Louvain, Belgium.;Katholieke Univ Leuven Hosp, B-3000 Louvain, Belgium..
    Dupont, Patrick
    Katholieke Univ Leuven, Lab Cognit Neurol, B-3000 Louvain, Belgium.;Katholieke Univ Leuven, Leuven Inst Neurosci & Dis, Alzheimer Res Ctr, B-3000 Louvain, Belgium..
    Hilven, Kelly
    Katholieke Univ Leuven, Lab Neuroimmunol, B-3000 Louvain, Belgium..
    Poesen, Koen
    Katholieke Univ Leuven, Lab Mol Neurobiomarker Res, B-3000 Louvain, Belgium.;UZ Leuven, Lab Med, B-3000 Louvain, Belgium..
    Vandenberghe, Rik
    Katholieke Univ Leuven, Lab Cognit Neurol, B-3000 Louvain, Belgium.;Katholieke Univ Leuven, Leuven Inst Neurosci & Dis, Alzheimer Res Ctr, B-3000 Louvain, Belgium.;Univ Hosp Leuven, Dept Neurol, B-3000 Louvain, Belgium..
    Diagnostic value of cerebrospinal fluid A beta ratios in preclinical Alzheimer's disease2015In: Alzheimer's Research & Therapy, ISSN 0065-6755, E-ISSN 1758-9193, Vol. 7, 75Article in journal (Refereed)
    Abstract [en]

    Introduction: In this study of preclinical Alzheimer's disease (AD) we assessed the added diagnostic value of using cerebrospinal fluid (CSF) A beta ratios rather than A beta 42 in isolation for detecting individuals who are positive on amyloid positron emission tomography (PET). Methods: Thirty-eight community-recruited cognitively intact older adults (mean age 73, range 65-80 years) underwent F-18-flutemetamol PET and CSF measurement of A beta 1-42, A beta 1-40, A beta 1-38, and total tau (ttau). F-18-flutemetamol retention was quantified using standardized uptake value ratios in a composite cortical region (SUVRcomp) with reference to cerebellar grey matter. Based on a prior autopsy validation study, the SUVRcomp cut-off was 1.57. Sensitivities, specificities and cut-offs were defined based on receiver operating characteristic analysis with CSF analytes as variables of interest and F-18-flutemetamol positivity as the classifier. We also determined sensitivities and CSF cut-off values at fixed specificities of 90 % and 95 %. Results: Seven out of 38 subjects (18 %) were positive on amyloid PET. A beta 42/ttau, A beta 42/A beta 40, A beta 42/A beta 38, and A beta 42 had the highest accuracy to identify amyloid-positive subjects (area under the curve (AUC) >= 0.908). A beta 40 and A beta 38 had significantly lower discriminative power (AUC = 0.571). When specificity was fixed at 90 % and 95 %, A beta 42/ttau had the highest sensitivity among the different CSF markers (85.71 % and 71.43 %, respectively). Sensitivity of A beta 42 alone was significantly lower under these conditions (57.14 % and 42.86 %, respectively). Conclusion: For the CSF-based definition of preclinical AD, if a high specificity is required, our data support the use of A beta 42/ttau rather than using A beta 42 in isolation.

  • 9. Adams, D.
    et al.
    Coelho, T.
    Suhr, Ole
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Conceicao, I.
    Waddington-Cruz, M.
    Schmidt, H.
    Campistol, J.
    Pouget, J.
    Buades, J.
    Falzone, R.
    Harrop, J.
    De Frutos, R.
    Butler, J.
    Cehelsky, J.
    Nochur, S.
    Vaishnaw, A.
    Gollob, J.
    Interim results from phase ii trial of aln-ttr02, a novel RNAi therapeutic for the treatment of familial amyloidotic polyneuropathy2013In: Journal of the peripheral nervous system, ISSN 1085-9489, E-ISSN 1529-8027, Vol. 18, no Supplement 2, 1-2 p.Article in journal (Other academic)
  • 10. Adams, David
    et al.
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hund, Ernst
    Obici, Laura
    Tournev, Ivailo
    Campistol, Josep M.
    Slama, Michel S.
    Hazenberg, Bouke P.
    Coelho, Teresa
    First European consensus for diagnosis, management, and treatment of transthyretin familial amyloid polyneuropathy2016In: Current Opinion in Neurology, ISSN 1350-7540, E-ISSN 1473-6551, Vol. 29, S14-S26 p.Article in journal (Refereed)
    Abstract [en]

    Purpose of review Early and accurate diagnosis of transthyretin familial amyloid polyneuropathy (TTR-FAP) represents one of the major challenges faced by physicians when caring for patients with idiopathic progressive neuropathy. There is little consensus in diagnostic and management approaches across Europe. Recent findings The low prevalence of TTR-FAP across Europe and the high variation in both genotype and phenotypic expression of the disease means that recognizing symptoms can be difficult outside of a specialized diagnostic environment. The resulting delay in diagnosis and the possibility of misdiagnosis can misguide clinical decision-making and negatively impact subsequent treatment approaches and outcomes. Summary This review summarizes the findings from two meetings of the European Network for TTR-FAP (ATTReuNET). This is an emerging group comprising representatives from 10 European countries with expertise in the diagnosis and management of TTR-FAP, including nine National Reference Centres. The current review presents management strategies and a consensus on the gold standard for diagnosis of TTR-FAP as well as a structured approach to ongoing multidisciplinary care for the patient. Greater communication, not just between members of an individual patient's treatment team, but also between regional and national centres of expertise, is the key to the effective management of TTR-FAP.

  • 11. Adams, David
    et al.
    Suhr, Ole
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Conceicao, Isabel
    Waddington-Cruz, Marcia
    Schmidt, Hartmut
    Buades, Juan
    Campistol, Josep
    Pouget, Jean
    Berk, John
    Coelho, Teresa
    Phase 2 open-label extension study of patisiran, an investigational RNAi therapeutic for the treatment of familial amyloid polyneuropathy2015In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 86, no 11Article in journal (Other academic)
  • 12.
    Addo, Rebecka N.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Stockholm Univ, Dept Psychol, Gosta Ekman Lab, Frescati Hagvag 9A, S-10691 Stockholm, Sweden..
    Wiens, Stefan
    Stockholm Univ, Dept Psychol, Gosta Ekman Lab, Frescati Hagvag 9A, S-10691 Stockholm, Sweden..
    Nord, Marie
    Stockholm Univ, Dept Psychol, Gosta Ekman Lab, Frescati Hagvag 9A, S-10691 Stockholm, Sweden..
    Larsson, Maria
    Stockholm Univ, Dept Psychol, Gosta Ekman Lab, Frescati Hagvag 9A, S-10691 Stockholm, Sweden..
    Olfactory Functions in Adults With Autism Spectrum Disorders2017In: Perception, ISSN 0301-0066, E-ISSN 1468-4233, Vol. 46, no 3-4, 530-537 p.Article in journal (Refereed)
    Abstract [en]

    Autism spectrum disorders (ASD) are often characterized by atypical sensory behavior (hyperor hyporeactivity) although evidence is scarce regarding olfactory abilities in ASD; 16 adults with high-functioning ASD (mean age: 38.2, SD: 9.7) and 14 healthy control subjects (mean age: 42.0 years, SD: 12.5) were assessed in odor threshold, free and cued odor identification, and perceived pleasantness, intensity, and edibility of everyday odors. Although results showed no differences between groups, the Bayes Factors (close to 1) suggested that the evidence for no group differences on the threshold and identification tests was inconclusive. In contrast, there was some evidence for no group differences on perceived edibility (BF01 = 2.69) and perceived intensity (BF01 = 2.80). These results do not provide conclusive evidence for or against differences between ASD and healthy controls on olfactory abilities. However, they suggest that there are no apparent group differences in subjective ratings of odors.

  • 13.
    Adlerz, Linda
    et al.
    Stockholm University, Faculty of Science, Department of Neurochemistry and Neurotoxicology.
    Beckman, Marie
    Stockholm University, Faculty of Science, Department of Neurochemistry and Neurotoxicology.
    Holback, Sofia
    Stockholm University, Faculty of Science, Department of Neurochemistry and Neurotoxicology.
    Tehranian, Roya
    Stockholm University, Faculty of Science, Department of Neurochemistry and Neurotoxicology.
    Cortés Toro, Veronica
    Stockholm University, Faculty of Science, Department of Neurochemistry and Neurotoxicology.
    Iverfeldt, Kerstin
    Stockholm University, Faculty of Science, Department of Neurochemistry and Neurotoxicology.
    Accumulation of the amyloid precursor-like protein APLP2 and reduction of APLP1 in retinoic acid-differentiated human neuroblastoma cells upon curcumin-induced neurite retraction2003In: Brain Research. Molecular Brain Research, ISSN 0169-328X, E-ISSN 1872-6941, Vol. 119, no 1, 62-72 p.Article in journal (Refereed)
    Abstract [en]

    Amyloid precursor protein (APP) belongs to a conserved gene family, also including the amyloid precursor-like proteins, APLP1 and APLP2. The function of these three proteins is not yet fully understood. One of the proposed roles of APP is to promote neurite outgrowth. The aim of this study was to investigate the regulation of the expression levels of APP family members during neurite outgrowth. We observed that retinoic acid (RA)-induced neuronal differentiation of human SH-SY5Y cells resulted in increased expression of APP, APLP1 and APLP2. We also examined the effect of the NFκB, AP-1 and c-Jun N-terminal kinase inhibitor curcumin (diferuloylmethane) on the RA-induced expression levels of these proteins. We found that treatment with curcumin counteracted the RA-induced mRNA expression of all APP family members. In addition, we observed that curcumin treatment resulted in neurite retraction without any effect on cell viability. Surprisingly, curcumin had differential effects on the APLP protein levels in RA-differentiated cells. RA-induced APLP1 protein expression was blocked by curcumin, while the APLP2 protein levels were further increased. APP protein levels were not affected by curcumin treatment. We propose that the sustained levels of APP and the elevated levels of APLP2, in spite of the reduced mRNA expression, are due to altered proteolytic processing of these proteins. Furthermore, our results suggest that APLP1 does not undergo the same type of regulated processing as APP and APLP2.

  • 14.
    Adlerz, Linda
    et al.
    Stockholm University, Faculty of Science, Department of Neurochemistry and Neurotoxicology.
    Soomets, Ursel
    Stockholm University, Faculty of Science, Department of Neurochemistry and Neurotoxicology. University of Tartu, Estonia.
    Holmlund, Linda
    Stockholm University, Faculty of Science, Department of Neurochemistry and Neurotoxicology.
    Virland, Saade
    Langel, Ülo
    Stockholm University, Faculty of Science, Department of Neurochemistry and Neurotoxicology.
    Iverfeldt, Kerstin
    Stockholm University, Faculty of Science, Department of Neurochemistry and Neurotoxicology.
    Down-regulation of amyloid precursor protein by peptide nucleic acid oligomer in cultured rat primary neurons and astrocytes2003In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 336, no 1, 55-59 p.Article in journal (Refereed)
    Abstract [en]

    The amyloid precursor protein (APP) and its proteolytic cleavage products, the amyloid P peptides, have been implicated as a cause of Alzheimer's disease. Peptide nucleic acids (PNA), the DNA mimics, have been shown to block the expression of specific proteins at both transcriptional and translational levels. Generally, the cellular uptake of PNA is low. However, recent studies have indicated that the effect of unmodified antisense PNA uptake is more pronounced in nervous tissue. In this study we have shown that biotinylated PNA directed to the initiator codon region of the APP mRNA (-4 - +11) was taken up into the cytoplasm of primary rat cerebellar granule cells and cortical astrocytes, using fluorescence and confocal microscopy studies. Uptake of PNA was faster in neurons than in astrocytes. Western blotting analysis showed that APP was strongly down-regulated in both neurons and astrocytes. Thus, unmodified PNA can be used for studies on the function of APP in neurons and astrocytes.

  • 15.
    Aghajani, Moji
    et al.
    Department of Child and Adolescent Psychiatry, Curium, Leiden University Medical Center, Leiden, the Netherlands; Leiden Institute for Brain and Cognition (LIBC), Leiden, the Netherlands; Department of Psychiatry, VU University Medical Center, Amsterdam, the Netherlands.
    Colins, Olivier F.
    Department of Child and Adolescent Psychiatry, Curium, Leiden University Medical Center, Leiden, the Netherlands; Leiden Institute for Brain and Cognition (LIBC), Leiden, the Netherlands; School of Law, Psychology, and Social Work, Örebro University, Örebro, Sweden.
    Klapwijk, Eduard T.
    Department of Child and Adolescent Psychiatry, Curium, Leiden University Medical Center, Leiden, the Netherlands; Leiden Institute for Brain and Cognition (LIBC), Leiden, the Netherlands.
    Veer, Ilya M.
    Division of Mind and Brain Research, Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin, Berlin, Germany.
    Andershed, Henrik
    Örebro University, School of Law, Psychology and Social Work, Örebro University, Sweden.
    Popma, Arne
    Department of Child and Adolescent Psychiatry, VU University Medical Center, Amsterdam, the Netherlands; Faculty of Law, Leiden University, Institute of Criminal Law and Criminology, Leiden, the Netherlands.
    van der Wee, Nic J.
    Leiden Institute for Brain and Cognition (LIBC), Leiden, the Netherlands; Department of Psychiatry, Leiden University Medical Center, Leiden, the Netherlands.
    Vermeiren, Robert R. J. M.
    Department of Child and Adolescent Psychiatry, Curium, Leiden University Medical Center, Leiden, the Netherlands; Leiden Institute for Brain and Cognition (LIBC), Leiden, the Netherlands.
    Dissociable relations between amygdala subregional networks and psychopathy trait dimensions in conduct-disordered juvenile offenders2016In: Human Brain Mapping, ISSN 1065-9471, E-ISSN 1097-0193, Vol. 37, no 11, 4017-4033 p.Article in journal (Refereed)
    Abstract [en]

    Psychopathy is a serious psychiatric phenomenon characterized by a pathological constellation of affective (e.g., callous, unemotional), interpersonal (e.g., manipulative, egocentric), and behavioral (e.g., impulsive, irresponsible) personality traits. Though amygdala subregional defects are suggested in psychopathy, the functionality and connectivity of different amygdala subnuclei is typically disregarded in neurocircuit-level analyses of psychopathic personality. Hence, little is known of how amygdala subregional networks may contribute to psychopathy and its underlying trait assemblies in severely antisocial people. We addressed this important issue by uniquely examining the intrinsic functional connectivity of basolateral (BLA) and centromedial (CMA) amygdala networks in relation to affective, interpersonal, and behavioral traits of psychopathy, in conduct-disordered juveniles with a history of serious delinquency (N = 50, mean age = 16.83 ± 1.32). As predicted, amygdalar connectivity profiles exhibited dissociable relations with different traits of psychopathy. Interpersonal psychopathic traits not only related to increased connectivity of BLA and CMA with a corticostriatal network formation accommodating reward processing, but also predicted stronger CMA connectivity with a network of cortical midline structures supporting sociocognitive processes. In contrast, affective psychopathic traits related to diminished CMA connectivity with a frontolimbic network serving salience processing and affective responding. Finally, behavioral psychopathic traits related to heightened BLA connectivity with a frontoparietal cluster implicated in regulatory executive functioning. We suggest that these trait-specific shifts in amygdalar connectivity could be particularly relevant to the psychopathic phenotype, as they may fuel a self-centered, emotionally cold, and behaviorally disinhibited profile.

  • 16.
    Aghanavesi, Somayeh
    et al.
    Computer Engineering, School of Technology and Business Studies, Dalarna University, Borlänge, Sweden.
    Memedi, Mevludin
    Örebro University, Örebro University School of Business.
    Dougherty, Mark
    Computer Engineering, School of Technology and Business Studies, Dalarna University, Borlänge, Sweden.
    Nyholm, Dag
    Dept. of Neuroscience, Neurology, Uppsala University, Uppsala, Sweden.
    Westin, Jerker
    Computer Engineering, School of Technology and Business Studies, Dalarna University, Borlänge, Sweden.
    Measuring temporal irregularity in spiral drawings of patients with Parkinson’s disease2017In: Abstracts of the 21st International Congress of Parkinson's Disease and Movement Disorders, John Wiley & Sons, 2017, Vol. 32Conference paper (Other (popular science, discussion, etc.))
    Abstract [en]

    Objective: The aim of this work is to evaluate clinimetric properties of a method for measuring Parkinson’s disease (PD) upper limb temporal irregularities during spiral drawing tasks.

    Background: Basal ganglia fluctuations of PD patients are associated with motor symptoms and relating them to objective sensor-based measures may facilitate the assessment of temporal irregularities, which could be difficult to be assessed visually. The present study investigated the upper limb temporal irregularity of patients at different stages of PD and medication time points.

    Methods: Nineteen PD patients and 22 healthy controls performed repeated spiral drawing tasks on a smartphone. Patients performed the tests before a single levodopa dose and at specific time intervals after the dose was given. Three movement disorder specialists rated the videos of patients' performance according to six items of UPDRS-III, dyskinesia (Dys), and Treatment Response Scale (TRS). A temporal irregularity score (TIS) was developed using approximate entropy (ApEn) method. Differences in mean TIS between two groups of patients and healthy subjects, and also across four subject groups: early, intermediate, advanced patients and, healthy subjects were assessed. The relative ability of TIS to detect changes from baseline (no medication) to later time points when patients were on medication was assessed. Correlations between TIS and clinical rating scales were assessed by Pearson correlation coefficients and test-retest reliability of TIS was measured by intra-class correlation coefficients (ICC).

    Results: The mean TIS was significantly different between healthy subjects and patients (P<0.0001). When assessing the changes in relation to treatment, clinical-based scores (TRS and Dys) had better responsiveness than TIS. However, the TIS was able to capture changes from Off to On, and the wearing off effects. Correlations between TIS and clinical scales were low indicating poor validity. Test-retest reliability correlation coefficient of the mean TIS was good (ICC=0.67).

    Conclusions: Our study found that TIS was able to differentiate spiral drawings drawn by patients from those drawn by healthy subjects. In addition, TIS could capture changes throughout the levodopa cycle.TIS was weakly correlated to clinical ratings indicating that TIS measures high frequency upper limb temporal irregularities that could be difficult to be detected during clinical observations.

  • 17.
    Agnvall, Beatrix
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Bélteky, Johan
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Brain size is reduced by selectionfor tameness in Red Junglefowl–correlated effects in vital organs2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, 3306Article in journal (Refereed)
    Abstract [en]

    During domestication animals have undergone changes in size of brain and other vital organs. We hypothesize that this could be a correlated effect to increased tameness. Red Junglefowl (ancestors of domestic chickens) were selected for divergent levels of fear of humans for five generations. The parental (P0) and the fifth selected generation (S5) were culled when 48–54 weeks old and the brains were weighed before being divided into telencephalon, cerebellum, mid brain and optic lobes. Each single brain part as well as the liver, spleen, heart and testicles were also weighed. Brains of S5 birds with high fear scores (S5 high) were heavier both in absolute terms and when corrected for body weight. The relative weight of telencephalon (% of brain weight) was significantly higher in S5 high and relative weight of cerebellum was lower. Heart, liver, testes and spleen were all relatively heavier (% of body weight) in S5 high. Hence, selection for tameness has changed the size of the brain and other vital organs in this population and may have driven the domesticated phenotype as a correlated response.

  • 18.
    Agosti, F.
    et al.
    Univ La Plata, CONICET, Multidisciplinary Inst Cell Biol IMBICE, Electrophysiol Lab, La Plata, Buenos Aires, Argentina.;CIC, Comis Invest Prov Buenos Aires, La Plata, Buenos Aires, Argentina..
    Cordisco Gonzalez, S.
    Univ La Plata, CONICET, Multidisciplinary Inst Cell Biol IMBICE, Electrophysiol Lab, La Plata, Buenos Aires, Argentina.;CIC, Comis Invest Prov Buenos Aires, La Plata, Buenos Aires, Argentina..
    Martinez Damonte, V.
    Univ La Plata, CONICET, Multidisciplinary Inst Cell Biol IMBICE, Electrophysiol Lab, La Plata, Buenos Aires, Argentina.;CIC, Comis Invest Prov Buenos Aires, La Plata, Buenos Aires, Argentina..
    Tolosa, M. J.
    Univ La Plata, CONICET, Multidisciplinary Inst Cell Biol IMBICE, Electrophysiol Lab, La Plata, Buenos Aires, Argentina.;CIC, Comis Invest Prov Buenos Aires, La Plata, Buenos Aires, Argentina..
    Di Siervi, N.
    Univ Buenos Aires, CONICET, ININFA, Inst Invest Farmacol, Buenos Aires, DF, Argentina..
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Davio, C.
    Univ Buenos Aires, CONICET, ININFA, Inst Invest Farmacol, Buenos Aires, DF, Argentina..
    Perello, M.
    CIC, Comis Invest Prov Buenos Aires, La Plata, Buenos Aires, Argentina.;Univ La Plata, CONICET, Multidisciplinary Inst Cell Biol, IMBICE,Neurophysiol Lab, La Plata, Buenos Aires, Argentina..
    Raingo, J.
    Univ La Plata, CONICET, Multidisciplinary Inst Cell Biol IMBICE, Electrophysiol Lab, La Plata, Buenos Aires, Argentina.;CIC, Comis Invest Prov Buenos Aires, La Plata, Buenos Aires, Argentina..
    Melanocortin 4 Receptor Constitutive Activity Inhibits L-Type Voltage-Gated Calcium Channels In Neurons2017In: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Vol. 346, 102-112 p.Article in journal (Refereed)
    Abstract [en]

    The melanocortin 4 receptor (MC4R) is a G protein-coupled receptor (GPCR) that is expressed in several brain nuclei playing a crucial role in the regulation of energy balance controlling the homeostasis of the organism. It displays both agonist-evoked and constitutive activity, and moreover, it can couple to different G proteins. Most of the research on MC4R has been focused on agonist-induced activity, while the molecular and cellular basis of MC4R constitutive activity remains scarcely studied. We have previously shown that neuronal N-type voltage-gated calcium channels (Ca(V)2.2) are inhibited by MC4R agonist-dependent activation, while the Ca-V subtypes that carry L- and P/Q-type current are not. Here, we tested the hypothesis that MC4R constitutive activity can affect Ca-V, with focus on the channel subtypes that can control transcriptional activity coupled to depolarization (L-type, Ca(V)1.2/1.3) and neurotransmitter release (N- and P/Q-type, Ca(V)2.2 and Ca(V)2.1). We found that MC4R constitutive activity inhibits specifically Ca(V)1.2/1.3 and Ca(V)2.1 subtypes of Ca-V. We also explored the signaling pathways mediating this inhibition, and thus propose that agonist-dependent and basal MC4R activation modes signal differentially through G(s) and G(i/o) pathways to impact on different Ca-V subtypes. In addition, we found that chronic incubation with MC4R endogenous inverse agonist, agouti and agouti-related peptide (AgRP), occludes Ca-V inhibition in a cell line and in amygdaloid complex cultured neurons as well. Thus, we define new mechanisms of control of the main mediators of depolarization-induced calcium entry into neurons by a GPCR that displays constitutive activity.

  • 19. Agosti, Francina
    et al.
    Lopez Soto, Eduardo J.
    Cabral, Agustina
    Castrogiovanni, Daniel
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Perello, Mario
    Raingo, Jesica
    Melanocortin 4 receptor activation inhibits presynaptic N-type calcium channels in amygdaloid complex neurons2014In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 40, no 5, 2755-2765 p.Article in journal (Refereed)
    Abstract [en]

    The melanocortin 4 receptor (MC4R) is a G protein-coupled receptor involved in food intake and energy expenditure regulation. MC4R activation modifies neuronal activity but the molecular mechanisms by which this regulation occurs remain unclear. Here, we tested the hypothesis that MC4R activation regulates the activity of voltage-gated calcium channels and, as a consequence, synaptic activity. We also tested whether the proposed effect occurs in the amygdala, a brain area known to mediate the anorexigenic actions of MC4R signaling. Using the patch-clamp technique, we found that the activation of MC4R with its agonist melanotan II specifically inhibited 34.5 +/- 1.5% of N-type calcium currents in transiently transfected HEK293 cells. This inhibition was concentration-dependent, voltage-independent and occluded by the G(s) pathway inhibitor cholera toxin. Moreover, we found that melanotan II specifically inhibited 25.9 +/- 2.0% of native N-type calcium currents and 55.4 +/- 14.4% of evoked inhibitory postsynaptic currents in mouse cultured amygdala neurons. Invivo, we found that the MC4R agonist RO27-3225 increased the marker of cellular activity c-Fos in several components of the amygdala, whereas the N-type channel blocker conotoxin GVIA increased c-Fos expression exclusively in the central subdivision of the amygdala. Thus, MC4R specifically inhibited the presynaptic N-type channel subtype, and this inhibition may be important for the effects of melanocortin in the central subdivision of the amygdala.

  • 20.
    Agoston, Denes V.
    et al.
    Uniformed Serv Univ Hlth Sci, Dept Anat, Bethesda, MD 20814 USA.;Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Sköld, Mattias K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery. Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Editorial: When Physics Meets Biology; Biomechanics and Biology of traumatic Brain injury2016In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 7, 91Article in journal (Other academic)
  • 21.
    Ahl, Rebecka
    et al.
    Örebro University, School of Medical Sciences. Division of Trauma and Emergency Surgery, Department of Surgery, Karolinska University Hospital, Stockholm, Sweden ; .
    Thelin, Eric Peter
    Department of Clinical Neuroscience, Karolinska Institutet, Solna, Stockholm, Sweden.
    Sjölin, Gabriel
    Orebro University Hospital. Division of Trauma and Emergency Surgery, Department of Surgery, Orebro University Hospital, Orebro, Sweden.
    Bellander, Bo Michael
    Department of Clinical Neuroscience, Karolinska Institutet, Solna, Stockholm, Sweden.
    Riddez, Louis
    Division of Trauma and Emergency Surgery, Department of Surgery, Karolinska University Hospital, Stockholm, Sweden.
    Talving, Peep
    Department of Surgery, Tartu University Hospital, Tartu, Estonia.
    Mohseni, Shahin H.
    Örebro University, School of Medical Sciences. Division of Trauma and Emergency Surgery, Department of Surgery, Karolinska University Hospital, Stockholm, Sweden; Division of Trauma and Emergency Surgery, Department of Surgery, Orebro University Hospital, Orebro, Sweden.
    β-Blocker after severe traumatic brain injury is associated with better long-term functional outcome: a matched case control study.2017In: European Journal of Trauma and Emergency Surgery, ISSN 1863-9933, E-ISSN 1863-9941Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Severe traumatic brain injury (TBI) is the predominant cause of death and disability following trauma. Several studies have observed improved survival in TBI patients exposed to β-blockers, however, the effect on functional outcome is poorly documented.

    METHODS: Adult patients with severe TBI (head AIS ≥ 3) were identified from a prospectively collected TBI database over a 5-year period. Patients with neurosurgical ICU length of stay <48 h and those dying within 48 h of admission were excluded. Patients exposed to β-blockers ≤ 48 h after admission and who continued with treatment until discharge constituted β-blocked cases and were matched to non β-blocked controls using propensity score matching. The outcome of interest was Glasgow Outcome Scores (GOS), as a measure of functional outcome up to 12 months after injury. GOS ≤ 3 was considered a poor outcome. Bivariate analysis was deployed to determine differences between groups. Odds ratio and 95% CI were used to assess the effect of β-blockers on GOS.

    RESULTS: 362 patients met the inclusion criteria with 21% receiving β-blockers during admission. After propensity matching, 76 matched pairs were available for analysis. There were no statistical differences in any variables included in the analysis. Mean hospital length of stay was shorter in the β-blocked cases (18.0 vs. 26.8 days, p < 0.01). The risk of poor long-term functional outcome was more than doubled in non-β-blocked controls (OR 2.44, 95% CI 1.01-6.03, p = 0.03).

    CONCLUSION: Exposure to β-blockers in patients with severe TBI appears to improve functional outcome. Further prospective randomized trials are warranted.

  • 22. Ahlström, Gerd
    et al.
    Lindvall, B.
    Wenneberg, Stig
    Örebro University, Department of Nursing and Caring Sciences.
    Gunnarsson, L. G.
    Örebro University, Department of Clinical Medicine.
    A comprehensive rehabilitation programme tailored to the needs of adults with muscular dystrophy2006In: Clinical Rehabilitation, ISSN 0269-2155, E-ISSN 1477-0873, Vol. 20, no 2, 132-141 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To assess if activities of daily living (ADL), coping and quality of life could be improved in adults with muscular dystrophy through a comprehensive rehabilitation programme. DESIGN: Quasi-experimental, controlled clinical study comparing patients with similar age and disease aspects. SETTING: Two different counties in Sweden, being either study or control setting. SUBJECTS: The study group comprised 37 adults (21 women, 16 men; mean age 50 years), while the control group comprised 39 people (25 women, 14 men; mean age 46 years). INTERVENTIONS: Four rehabilitation sessions tailored to different medical, physical and psychosocial needs of the patients, comprising a total of 10 days over a period of 18 months. MAIN MEASURES: ADL, the Mental Adjustment to Cancer Scale measuring coping strategies, the Sickness Impact Profile measuring health-related quality of life, the Hospital Anxiety and Depression Scale, and the Psychosocial Well-being Questionnaire. RESULTS: No significant differences were found between groups with regard to the outcome measures. There was increased dependence on others in ADL after 18 months in both groups, but it was more pronounced in the control group. Furthermore, a clear trend was observed in the data with regard to coping patterns, the control group using more coping strategies such as 'Helplessness/hopelessness' (P= 0.057), 'Anxious preoccupation' (P = 0.085) and 'Fatalistic' (P= 0.073) when being compared to the study group. CONCLUSIONS: No apparent effects on ADL were found from the rehabilitation programme, although there was a tendency of reduction of maladaptive coping patterns in the study group. This initial study may provide the rationale and basis for a randomized controlled trial.

  • 23.
    Ahlström, Isabell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotherapy.
    Hellström, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotherapy.
    Emtner, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotheraphy. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Anens, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotherapy.
    Reliability of the Swedish version of the Exercise Self-Efficacy Scale (S-ESES): a test-retest study in adults with neurological disease2015In: Physiotherapy Theory and Practice, ISSN 0959-3985, E-ISSN 1532-5040, Vol. 31, no 3, 194-199 p.Article in journal (Refereed)
    Abstract [en]

    Objective: To examine the test-retest reliability of the Swedish translated version of the Exercise Self-Efficacy Scale (S-ESES) in people with neurological disease and to examine internal consistency.

    Design: Test-retest study.

    Subjects: A total of 30 adults with neurological diseases including: Parkinson's disease; Multiple Sclerosis; Cervical Dystonia; and Charcot Marie Tooth disease.

    Method: The S-ESES was sent twice by surface mail. Completion interval mean was 16 days apart. Weighted kappa, intraclass correlation coefficient 2,1 [ICC (2,1)], standard error of measurement (SEM), also expressed as a percentage value (SEM%), and Cronbach's alpha were calculated.

    Results: The relative reliability of the test-retest results showed substantial agreement measured using weighted kappa (MD = 0.62) and a very high-reliability ICC (2,1) (0.92). Absolute reliability measured using SEM was 5.3 and SEM% was 20.7. Excellent internal consistency was shown, with an alpha coefficient of 0.91 (test 1) and 0.93 (test 2).

    Conclusion: The S-ESES is recommended for use in research and in clinical work for people with neurological diseases. The low-absolute reliability, however, indicates a limited ability to measure changes on an individual level.

  • 24.
    Ahmad, Abdulbaghi
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Childhood trauma and posttraumatic stress disorder: A developmental and cross-cultural approach1999Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis aims to identify child-specific cross-cultural protecting and vulnerability factors regarding traumatic experiences and posttraumatic stress reactions. Children between 6-18 years were interviewed from three different socio-cultural backgrounds. In Iraqi Kurdistan, 20 participants in a mass-escape tragedy (MET), 54 orphans and 45 survivors of the genocide operation "Anfal" were interviewed. In Sweden, a sample of 32 Kurdistanian refugee children and a comparable Swedish sample were included. The frequencies of posttraumatic stress disorder (PTSD) were 20%, 43%. 87%, 9,7% and 12.5% respectively.

    The relatively low frequencies of PTSD in the follow-up sample 2 months, 4 months, 14 months and 26 months after the MET suggest the child functioning in a complete, authoritative family, as a protecting factor. The significant of this developmentally based child-specific functioning level within the supportive family system can also explain the fluctuating PTSD-related symptom scores in this sample parallel to the changes in the socio-economic situation in the region. The over time decrease in behavioural problems among fostercare orphans and their low PTSD frequencies as compared with the increase in behavioural problems and the high PTSD frequencies among orphanage samples further support this suggestion. Child trauma scores and captivity duration predicted for PTSD in "Anfal" survivors, irrespective of parents' trauma scores and PTSD or fathers re-union with the family, suggesting child-specific vulnerability more than contagion effect. Despite PTSD, children in Kurdistan performed high functioning levels, probably indicating a child-specific manifestation of hypervigilance. The Kurdistanian refugee sample revealed lower lifetime reexperiencing PTSD symptom scores than the Swedish sample, indicating a healing effect on the former coming to Sweden and a resilience deficit for the later growing up in a highly sheltered society.

    There are more similarities than differences between children from Kurdistan and Sweden in reporting traumatic experiences and exhibiting posttraumatic stress symptoms. Developmentally based child characteristics have a determinant role as protective or vulnerability factors in childhood trauma and PTSD, even if socio-cultural factors also play a role.

  • 25.
    Ahmadi, Mahboobah
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Liu, Jing-Xia
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Andersen, Peter M
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Pedrosa-Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Human extraocular muscles in ALS2010In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, Vol. 51, no 7, 3494-3501 p.Article in journal (Refereed)
    Abstract [en]

    PURPOSE. To investigate the general morphology, fiber type content, and myosin heavy chain (MyHC) composition of extraocular muscles (EOMs) from postmortem donors with amyotrophic lateral sclerosis (ALS) and to evaluate whether EOMs are affected or truly spared in this disease. METHODS. EOM and limb muscle samples obtained at autopsy from ALS donors and EOM samples from four control donors were processed for immunohistochemistry with monoclonal antibodies against distinct MyHC isoforms and analyzed by SDS-PAGE. In addition, hematoxylin and eosin staining and nicotinamide tetrazolium reductase (NADH-TR) activity were studied. RESULTS. Wide heterogeneity was observed in the appearance of the different EOMs from each single donor and between donors, irrespective of ALS type or onset. Pathologic morphologic findings in ALS EOMs included presence of atrophic and hypertrophic fibers, either clustered in groups or scattered; increased amounts of connective tissue; and areas of fatty replacement. The population of fibers stained with anti-MyHCslow tonic was smaller than that of MyHCIpositive fibers and was mostly located in the orbital layer in most of the ALS EOM samples, whereas an identical staining pattern for both fiber populations was observed in the control specimens. MyHCembryonic was notably absent from the ALS EOMs. CONCLUSIONS. The EOMs showed signs of involvement with altered fiber type composition, contractile protein content, and cellular architecture. However, when compared to the limb muscles, the EOMs were remarkably preserved. EOMs are a useful model for the study of the pathophysiology of ALS.

  • 26.
    Aho, Anna-Carin
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Health and Caring Sciences.
    Hultsjö, Sally
    Region Jönköping ; Jönköping University.
    Hjelm, Katarina
    Linköping University.
    Experiences of being parents of young adults living with recessive limb-girdle muscular dystrophy from a salutogenic perspective2017In: Neuromuscular Disorders, ISSN 0960-8966, E-ISSN 1873-2364, Vol. 27, no 6, 585-595 p.Article in journal (Refereed)
    Abstract [en]

    Recessive limb-girdle muscular dystrophies (LGMD2) involve progressive muscle weakness. Parental support is important for young adults living with LGMD2, but no study has been identified focusing on the parents' experiences. The salutogenic perspective concentrates on how daily life is comprehended, managed and found meaningful, i.e. the person's sense of coherence. The aim of this study was to describe, from a salutogenic perspective, experiences of being parents of young adults living with LGMD2. Nineteen participants were included. Data were collected by semi-structured interviews and the self-administrated 13-item sense of coherence questionnaire. Interview data were analysed with content analysis and related to self-rated sense of coherence. The result shows experiences of being influenced, not only by thoughts and emotions connected to the disease but also by caregiving duties and the young adults' well-being. Simultaneously, difficulty in fully grasping the disease was expressed and uncertainty about progression created worries about future management. Trying their best to support their young adults to experience well-being and to live fulfilled lives, the importance of having a social network, support from concerned professionals and eventually access to personal assistance was emphasized. The need to have meaningful pursuits of one's own was also described. The median sense of coherence score was 68 (range 53–86). Those who scored high (≥68) described satisfaction with social network, external support provided, work and leisure activities to a greater extent than those who scored low (<68). The result shows that the young adults' disease has a major impact on the parents' lives. Assessment of how the parents comprehend, manage and find meaning in everyday life may highlight support needed to promote their health.

  • 27. Aho, Leena
    et al.
    Karkola, Kari
    Juusela, Jari
    Alafuzoff, Irina
    Department of Neuroscience and Neurology, University of Kuopio Finland .
    Heavy alcohol consumption and neuropathological lesions: a post-mortem human study2009In: Journal of Neuroscience Research, ISSN 0360-4012, E-ISSN 1097-4547, Vol. 87, no 12, 2786-2792 p.Article in journal (Refereed)
    Abstract [en]

    Epidemiological studies have indicated that excessive alcohol consumption leads to cognitive impairment, but the specific pathological mechanism involved remains unknown. The present study evaluated the association between heavy alcohol intake and the neuropathological hallmark lesions of the three most common neurodegenerative disorders, i.e., Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and vascular cognitive impairment (VCI), in post-mortem human brains. The study cohort was sampled from the subjects who underwent a medicolegal autopsy during a 6-month period in 1999 and it included 54 heavy alcohol consumers and 54 age- and gender-matched control subjects. Immunohistochemical methodology was used to visualize the aggregation of beta-amyloid, hyperphosphorylated tau, and alpha-synuclein and the extent of infarcts. In the present study, no statistically significant influence was observed for alcohol consumption on the extent of neuropathological lesions encountered in the three most common degenerative disorders. Our results indicate that alcohol-related dementia differs from VCI, AD, and DLB; i.e., it has a different etiology and pathogenesis.

  • 28.
    Ahrén-Moonga, Jennie
    et al.
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS).
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    von Blixten, Nils
    Rönnelid, Johan
    Holmgren, Sven
    af Klinteberg, Britt
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS). Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Levels of tumour necrosis factor-alpha and interleukin-6 in severely ill patients with eating disorders2011In: Neuropsychobiology, ISSN 0302-282X, E-ISSN 1423-0224, Vol. 63, no 1, 8-14 p.Article in journal (Refereed)
    Abstract [en]

    Background: The underlying pathophysiology of eating disorders (ED) is dependent on complex interactions between psychological, biological and social factors. The purpose of the present study was to examine a possible increase in cytokines indicating inflammation, as measured by tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in ED patients, and to explore possible relationships between cytokines and self-reported personality traits. Methods: Female patients with severe ED (n = 26) were recruited consecutively from an inpatient clinic and were compared to age-matched healthy females (n = 12). Commercial ELISA tests developed for the measurement of serum levels of TNF-α and IL-6 were employed. Personality traits were measured using Karolinska Scales of Personality. Results: The patient group displayed increased levels of the cytokine TNF-α and a tendency towards increased IL-6 levels. Spearman's rank correlation coefficient was used to examine possible relationships between levels of cytokines and personality traits. The results showed that IL-6 levels were positively related to both somatic and psychic anxiety and to aggression scales, such as irritability and suspicion. Increased levels of TNF-α, in turn, were significantly correlated with high scores on the depression-related anxiety scale Inhibition of Aggression. However, increased levels of cytokines in the ED group did not seem to be mainly associated with symptoms of depression. Conclusion: We cannot rule out the possibility that comorbid conditions in the group contribute to the higher cytokine values. Further studies need to explore the possible influence of cytokines on the severity of ED and whether this might be mediated or moderated by specific personality traits.

  • 29.
    Akerstedt, T.
    et al.
    Karolinska Inst, Clin Neurosci, Stockholm, Sweden.;Stockholm Univ, Stress Res Inst, Stockholm, Sweden..
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Theorell-Haglöw, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Gruber, G.
    Siesta Grp, Vienna, Austria..
    Schwarz, J.
    Stockholm Univ, Stress Res Inst, Stockholm, Sweden..
    The polysomnographical characteristics of women who have sought medical help for sleep problems - a large study of sleep macro and micro architeture2016In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 25, 90-90 p.Article in journal (Other academic)
  • 30. Akram, Harith
    et al.
    Limousin, Patricia
    Hyam, Jonathan
    Hariz, Marwan I.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London.
    Zrinzo, Ludvic
    Aim for the Suprasternal Notch: Technical Note to Avoid Bowstringing after Deep Brain Stimulation2015In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 93, no 4, 227-230 p.Article in journal (Refereed)
    Abstract [en]

    Background: Bowstringing may occur when excessive fibrosis develops around extension cables in the neck after deep brain stimulation (DBS) surgery. Though the occurrence of this phenomenon is rare, we have noted that it tends to cause maximal discomfort when the cables cross superficially over the convexity of the clavicle. We hypothesise that bowstringing may be avoided by directing the extension cables towards the suprasternal notch. Methods: When connecting DBS leads to an infraclavicular pectoral implantable pulse generator (IPG), tunnelling is directed towards the suprasternal I notch, before being directed laterally towards the IPG pocket. In previously operated patients with established fibrosis, the fibrous tunnel is opened and excised as far cranially as possible, allowing medial rerouting of cables. Using this approach, we reviewed our series of patients who underwent DBS surgery over 10 years. Results: In 429 patients, 7 patients (2%) with cables tunnelled over the convexity of the clavicle complaining of bowstringing underwent cable exploration and rerouting. This eliminated bowstringing and provided better cosmetic results. When the cable trajectory was initially directed towards the suprasternal notch, no bowstringing was observed. Conclusion:The tunnelling trajectory appears to influence postoperative incidence of fibrosis associated with DBS cables. Modifying the surgical technique may reduce the incidence of this troublesome adverse event. (C) 2015 S.Karger AG, Basel

  • 31. Akram, Harith
    et al.
    Sotiropoulos, Stamatios N.
    Jbabdi, Saad
    Georgiev, Dejan
    Mahlknecht, Philipp
    Hyam, Jonathan
    Foltynie, Thomas
    Limousin, Patricia
    De Vita, Enrico
    Jahanshahi, Marjan
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK.
    Ashburner, John
    Behrens, Tim
    Zrinzo, Ludvic
    Subthalamic deep brain stimulation sweet spots and hyperdirect cortical connectivity in Parkinson's disease2017In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 158, 332-345 p.Article in journal (Refereed)
    Abstract [en]

    Objectives: Firstly, to identify subthalamic region stimulation clusters that predict maximum improvement in rigidity, bradykinesia and tremor, or emergence of side-effects; and secondly, to map-out the cortical fingerprint, mediated by the hyperdirect pathways which predict maximum efficacy.

    Methods: High angular resolution diffusion imaging in twenty patients with advanced Parkinson's disease was acquired prior to bilateral subthalamic nucleus deep brain stimulation. All contacts were screened one-year from surgery for efficacy and side-effects at different amplitudes. Voxel-based statistical analysis of volumes of tissue activated models was used to identify significant treatment clusters. Probabilistic tractography was employed to identify cortical connectivity patterns associated with treatment efficacy.

    Results: All patients responded well to treatment (46% mean improvement off medication UPDRS-III [p < 0.0001]) without significant adverse events. Cluster corresponding to maximum improvement in tremor was in the posterior, superior and lateral portion of the nucleus. Clusters corresponding to improvement in bradykinesia and rigidity were nearer the superior border in a further medial and posterior location. The rigidity cluster extended beyond the superior border to the area of the zona incerta and Forel-H-2 field. When the clusters where averaged, the coordinates of the area with maximum overall efficacy was X = -10(-9.5), Y = -3(-1) and Z = -7(-3) in MNI(AC-PC) space. Cortical connectivity to primary motor area was predictive of higher improvement in tremor; whilst that to supplementary motor area was predictive of improvement in bradykinesia and rigidity; and connectivity to prefrontal cortex was predictive of improvement in rigidity.

    Interpretation: These findings support the presence of overlapping stimulation sites within the subthalamic nucleus and its superior border, with different cortical connectivity patterns, associated with maximum improvement in tremor, rigidity and bradykinesia.

  • 32. Akram, Harith
    et al.
    Wu, Chengyuan
    Hyam, Jonathan
    Foltynie, Thomas
    Limousin, Patricia
    De Vita, Enrico
    Yousry, Tarek
    Jahanshahi, Marjan
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, Queen Square, London, UK.
    Behrens, Timothy
    Ashburner, John
    Zrinzo, Ludvic
    L-Dopa Responsiveness Is Associated With Distinctive Connectivity Patterns in Advanced Parkinson's Disease2017In: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 32, no 6, 874-883 p.Article in journal (Refereed)
    Abstract [en]

    Background: Neuronal loss and dopamine depletion alter motor signal processing between cortical motor areas, basal ganglia, and the thalamus, resulting in the motor manifestations of Parkinson's disease. Dopamine replacement therapy can reverse these manifestations with varying degrees of improvement. Methods: To evaluate functional connectivity in patients with advanced Parkinson's disease and changes in functional connectivity in relation to the degree of response to L-dopa, 19 patients with advanced Parkinson's disease underwent resting-state functional magnetic resonance imaging in the on-medication state. Scans were obtained on a 3-Tesla scanner in 3x3x2.5mm(3) voxels. Seed-based bivariate regression analyses were carried out with atlas-defined basal ganglia regions as seeds, to explore relationships between functional connectivity and improvement in the motor section of the UPDRS-III following an L-dopa challenge. False discovery rate-corrected P was set at < 0.05 for a 2-tailed t test. Results: A greater improvement in UPDRS-III scores following L-dopa administration was characterized by higher resting-state functional connectivity between the prefrontal cortex and the striatum (P=0.001) and lower resting-state functional connectivity between the pallidum (P=0.001), subthalamic nucleus (P=0.003), and the paracentral lobule (supplementary motor area, mesial primary motor, and primary sensory areas). Conclusions: Our findings show characteristic basal ganglia resting-state functional connectivity patterns associated with different degrees of L-dopa responsiveness in patients with advanced Parkinson's disease. L-Dopa exerts a graduated influence on remapping connectivity in distinct motor control networks, potentially explaining some of the variance in treatment response.

  • 33. Al Nimer, Faiez
    et al.
    Elliott, Christina
    Bergman, Joakim
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Khademi, Mohsen
    Dring, Ann M
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Aeinehband, Shahin
    Bergenheim, Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Christensen, Jeppe Romme
    Sellebjerg, Finn
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Linington, Christopher
    Olsson, Tomas
    Piehl, Fredrik
    Lipocalin-2 is increased in progressive multiple sclerosis and inhibits remyelination2016In: Neurology: Neuroimmunology and neuroinflammation, ISSN 0948-6259, E-ISSN 2332-7812, Vol. 3, no 1, e191Article in journal (Refereed)
    Abstract [en]

    Objective: We aimed to examine the regulation of lipocalin-2 (LCN2) in multiple sclerosis (MS) and its potential functional relevance with regard to myelination and neurodegeneration. Methods: We determined LCN2 levels in 3 different studies: (1) in CSF and plasma from a case-control study comparing patients with MS (n = 147) with controls (n = 50) and patients with relapsing-remitting MS (n = 75) with patients with progressive MS (n = 72); (2) in CSF and brain tissue microdialysates from a case series of 7 patients with progressive MS; and (3) in CSF at baseline and 60 weeks after natalizumab treatment in a cohort study of 17 patients with progressive MS. Correlation to neurofilament light, a marker of neuroaxonal injury, was tested. The effect of LCN2 on myelination and neurodegeneration was studied in a rat in vitro neuroglial cell coculture model. Results: Intrathecal production of LCN2 was increased predominantly in patients with progressive MS (p < 0.005 vs relapsing-remitting MS) and displayed a positive correlation to neurofilament light (p = 0.005). Levels of LCN2 in brain microdialysates were severalfold higher than in the CSF, suggesting local production in progressive MS. Treatment with natalizumab in progressive MS reduced LCN2 levels an average of 13% (p < 0.0001). LCN2 was found to inhibit remyelination in a dose-dependent manner in vitro. Conclusions: LCN2 production is predominantly increased in progressive MS. Although this moderate increase does not support the use of LCN2 as a biomarker, the correlation to neurofilament light and the inhibitory effect on remyelination suggest that LCN2 might contribute to neurodegeneration through myelination-dependent pathways.

  • 34.
    Alafuzoff, Irina
    et al.
    Department of Neuroscience and Neurology, University of Kuopio Finland .
    Aho, L
    Helisalmi, S
    Mannermaa, A
    Soininen, H
    Beta-amyloid deposition in brains of subjects with diabetes2009In: Neuropathology and Applied Neurobiology, ISSN 0305-1846, E-ISSN 1365-2990, Vol. 35, no 1, 60-68 p.Article in journal (Refereed)
    Abstract [en]

    AIM:

    A causative association between diabetes mellitus (DM) and Alzheimer's disease (AD) has been suggested based on clinical and epidemiological studies. One hypothesis is that the link between DM and AD is related to the function of insulin-degrading enzyme (IDE), an enzyme that degrades not only insulin and pancreatic amylin but also beta-amyloid (Abeta). Thus, in diabetics, insulin and Abeta might compete for IDE and this might lead to an increase in Abeta. The objective of this study was to test the hypothesis that hyperinsulinaemia can elevate Abeta levels and thus contribute to AD pathology in humans.

    METHODS:

    Neuropathological examination was carried out employing conventional and immunohistochemical (IHC) methods of the brains obtained post mortem from 701 aged subjects.

    RESULTS:

    The loads of IHC/Abeta, silver stained neuritic plaques (NP) and neurofibrillary tangles (NFT) were significantly higher in subjects carrying the Apolipoprotein E e4 allele. In contrast, the loads of Abeta, NPs and NFT in the brains were not influenced by hyperglycaemia when comparing 134 diabetic with 567 non-diabetic subjects.

    CONCLUSIONS:

    We conclude that the hypothesis that hyperinsulinaemia would significantly elevate the Abeta load and thus increase the extent of AD pathology cannot be supported. Our result challenges the claim that DM is a direct risk factor of developing AD. Thus further studies on pathological lesions in demented diabetics should be conducted.

  • 35.
    Alafuzoff, Irina
    et al.
    Department of Neuroscience and Neurology, University of Kuopio Finland .
    Thal, Dietmar R.
    Arzberger, Thomas
    Bogdanovic, Nenad
    Al-Sarraj, Safa
    Bodi, Istvan
    Boluda, Susan
    Bugiani, Orso
    Duyckaerts, Charles
    Gelpi, Ellen
    Gentleman, Stephen
    Giaccone, Giorgio
    Graeber, Manuel
    Hortobagyi, Tibor
    Höftberger, Romana
    Ince, Paul
    Ironside, James W.
    Kavantzas, Nikolaos
    King, Andrew
    Korkolopoulou, Penelope
    Kovács, Gábor G.
    Meyronet, David
    Monoranu, Camelia
    Nilsson, Tatjana
    Parchi, Piero
    Patsouris, Efstratios
    Pikkarainen, Maria
    Revesz, Tamas
    Rozemuller, Annemieke
    Seilhean, Danielle
    Schulz-Schaeffer, Walter
    Streichenberger, Nathalie
    Wharton, Stephen B.
    Kretzschmar, Hans
    Assessment of beta-amyloid deposits in human brain: a study of the BrainNet Europe Consortium2009In: Acta Neuropathologica, ISSN 0001-6322, E-ISSN 1432-0533, Vol. 117, no 3, 309-320 p.Article in journal (Refereed)
    Abstract [en]

    beta-Amyloid (A-beta) related pathology shows a range of lesions which differ both qualitatively and quantitatively. Pathologists, to date, mainly focused on the assessment of both of these aspects but attempts to correlate the findings with clinical phenotypes are not convincing. It has been recently proposed in the same way as iota and alpha synuclein related lesions, also A-beta related pathology may follow a temporal evolution, i.e. distinct phases, characterized by a step-wise involvement of different brain-regions. Twenty-six independent observers reached an 81% absolute agreement while assessing the phase of A-beta, i.e. phase 1 = deposition of A-beta exclusively in neocortex, phase 2 = additionally in allocortex, phase 3 = additionally in diencephalon, phase 4 = additionally in brainstem, and phase 5 = additionally in cerebellum. These high agreement rates were reached when at least six brain regions were evaluated. Likewise, a high agreement (93%) was reached while assessing the absence/presence of cerebral amyloid angiopathy (CAA) and the type of CAA (74%) while examining the six brain regions. Of note, most of observers failed to detect capillary CAA when it was only mild and focal and thus instead of type 1, type 2 CAA was diagnosed. In conclusion, a reliable assessment of A-beta phase and presence/absence of CAA was achieved by a total of 26 observers who examined a standardized set of blocks taken from only six anatomical regions, applying commercially available reagents and by assessing them as instructed. Thus, one may consider rating of A-beta-phases as a diagnostic tool while analyzing subjects with suspected Alzheimer's disease (AD). Because most of these blocks are currently routinely sampled by the majority of laboratories, assessment of the A-beta phase in AD is feasible even in large scale retrospective studies.

  • 36.
    Alaie, Iman
    et al.
    Uppsala Univ, Dept Psychol, Uppsala, Sweden.
    Frick, Andreas
    Uppsala Univ, Dept Psychol, Uppsala, Sweden.
    Marteinsdottir, Ina
    Linköping Univ, Dept Clin & Expt Med, Linköping, Sweden.
    Hartvig, Per
    Univ Copenhagen, Dept Drug Design & Pharmacol, Copenhagen, Denmark.
    Tillfors, Maria
    Örebro University, School of Law, Psychology and Social Work, Örebro University, Sweden.
    Eriksson, Elias
    Univ Gothenburg, Dept Pharmacol, Gothenburg, Sweden.
    Fredrikson, Mats
    Uppsala Univ, Dept Psychol, Uppsala, Sweden.
    Furmark, Tomas
    Uppsala Univ, Dept Psychol, Uppsala, Sweden.
    Serotonin Synthesis Rate and the Tryptophan Hydroxylase-2 G-703T Polymorphism in Social Anxiety Disorder2014In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 75, no 9, 357S-357S p.Article in journal (Other academic)
  • 37. Alakurtti, Kati
    et al.
    Johansson, Jarkko J.
    Joutsa, Juho
    Laine, Matti
    Backman, Lars
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Rinne, Juha O.
    Long-term test-retest reliability of striatal and extrastriatal dopamine D-2/3 receptor binding: study with [C-11]raclopride and high-resolution PET2015In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 35, no 7, 1199-1205 p.Article in journal (Refereed)
    Abstract [en]

    We measured the long-term test-retest reliability of [C-11]raclopride binding in striatal subregions, the thalamus and the cortex using the bolus-plus-infusion method and a high-resolution positron emission scanner. Seven healthy male volunteers underwent two positron emission tomography (PET) [C-11]raclopride assessments, with a 5-week retest interval. D-2/3 receptor availability was quantified as binding potential using the simplified reference tissue model. Absolute variability (VAR) and intraclass correlation coefficient (ICC) values indicated very good reproducibility for the striatum and were 4.5%/0.82, 3.9%/0.83, and 3.9%/0.82, for the caudate nucleus, putamen, and ventral striatum, respectively. Thalamic reliability was also very good, with VAR of 3.7% and ICC of 0.92. Test-retest data for cortical areas showed good to moderate reproducibility (6.1% to 13.1%). Our results are in line with previous test-retest studies of [C-11]raclopride binding in the striatum. A novel finding is the relatively low variability of [C-11]raclopride binding, providing suggestive evidence that extrastriatal D-2/3 binding can be studied in vivo with [C-11]raclopride PET to be verified in future studies.

  • 38.
    Algurén, Beatrix
    et al.
    Institute for Health and Rehabilitation Sciences (IHRS), Unit for Biopsychosocial Health, Ludwig-Maximilians-University, Munich, Germany.
    Lundgren Nilsson, Åsa
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Nursing Science.
    Sunnerhagen, Katharina S.
    Functioning of patients with first-ever stroke six weeks after admission – a report from Sweden applying the International Classification of Functioning (ICF)2007Conference paper (Refereed)
  • 39.
    Ali, Zafar
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Human Molecular Genetics Laboratory, National Institute for Biotechnology and Genetic Engineering (NIBGE), PIEAS, 38000 Faisalabad, Pakistan.
    Klar, Joakim
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Jameel, Mohammad
    Human Molecular Genetics Laboratory, National Institute for Biotechnology and Genetic Engineering (NIBGE), PIEAS, 38000 Faisalabad, Pakistan.
    Khan, Kamal
    Human Molecular Genetics Laboratory, National Institute for Biotechnology and Genetic Engineering (NIBGE), PIEAS, 38000 Faisalabad, Pakistan.
    Fatima, Ambrin
    Human Molecular Genetics Laboratory, National Institute for Biotechnology and Genetic Engineering (NIBGE), PIEAS, 38000 Faisalabad, Pakistan.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Baig, Shahid
    Human Molecular Genetics Laboratory, National Institute for Biotechnology and Genetic Engineering (NIBGE), PIEAS, 38000 Faisalabad, Pakistan.
    Dahl, Niklas
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Novel SACS mutations associated with intellectual disability, epilepsy and widespread supratentorial abnormalities2016In: Journal of the Neurological Sciences, ISSN 0022-510X, E-ISSN 1878-5883, Vol. 371, 105-111 p.Article in journal (Refereed)
    Abstract [en]

    We describe eight subjects from two consanguineous families segregating with autosomal recessive childhood onset spastic ataxia, peripheral neuropathy and intellectual disability. The degree of intellectual disability varied from mild to severe and all four affected individuals in one family developed aggressive behavior and epilepsy. Using exome sequencing, we identified two novel truncating mutations (c.2656C>T (p.Gln886*)) and (c.4756_4760delAATCA (p.Asn1586Tyrfs*3)) in the SACS gene responsible for autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). MRI revealed typical cerebellar and pontine changes associated with ARSACS as well as multiple supratentorial changes in both families as likely contributing factors to the cognitive symptoms. Intellectual disability and behavioral abnormalities have been reported in some cases of ARSACS but are not a part of the characteristic triad of symptoms that includes cerebellar ataxia, spasticity and peripheral neuropathy. Our combined findings bring further knowledge to the phenotypic spectrum, neurodegenerative changes and genetic variability associated with the SACS gene of clinical and diagnostic importance.

  • 40.
    Alit, Abir
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine oncology.
    Grönberg, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Federspiel, B.
    Dept Pathol, Copenhagen, Denmark..
    Hjortland, G. O.
    Dept Oncol, Oslo, Norway..
    Ladekarl, M.
    Dept Oncol, Aarhus, Denmark..
    Langer, S. W.
    Dept Oncol, Copenhagen, Denmark..
    Welin, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine oncology.
    Knigge, U.
    Dept Surg C, Copenhagen, Denmark.;Dept Endocrinol PE, Copenhagen, Denmark..
    Sorbye, H.
    Dept Oncol, Bergen, Norway..
    Grimelius, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Tiensuu Janson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine oncology.
    Expression of Mutated p53 Protein in Gastroenteropancreatic Neuroendocrine Carcinoma (WHO G3)2016In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 103, 43-43 p.Article in journal (Refereed)
  • 41.
    Alm, Per A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Logopedi.
    Is it Thinking and not Feeling that influence variability of stuttering in social situations?: About stuttering and social cognition2015In: 10Th Oxford Dysfluency Conference, ODC 2014, 2015, 289-290 p.Conference paper (Refereed)
  • 42.
    Alm, Per A
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Dreimanis, Karolina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Neuropathic pain: transcranial electric motor cortex stimulation using high frequency random noise: Case report of a novel treatment2013In: Journal of Pain Research, ISSN 1178-7090, E-ISSN 1178-7090, Vol. 6, 479-486 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Electric motor cortex stimulation has been reported to be effective for many cases of neuropathic pain, in the form of epidural stimulation or transcranial direct current stimulation (tDCS). A novel technique is transcranial random noise stimulation (tRNS), which increases the cortical excitability irrespective of the orientation of the current. The aim of this study was to investigate the effect of tRNS on neuropathic pain in a small number of subjects, and in a case study explore the effects of different stimulation parameters and the long-term stability of treatment effects.

    METHODS: THE STUDY WAS DIVIDED INTO THREE PHASES: (1) a double-blind crossover study, with four subjects; (2) a double-blind extended case study with one responder; and (3) open continued treatment. The motor cortex stimulation consisted of alternating current random noise (100-600 Hz), varying from 0.5 to 10 minutes and from 50 to 1500 μA, at intervals ranging from daily to fortnightly.

    RESULTS: One out of four participants showed a strong positive effect (also compared with direct-current-sham, P = 0.006). Unexpectedly, this effect was shown to occur also for very weak (100 μA, P = 0.048) and brief (0.5 minutes, P = 0.028) stimulation. The effect was largest during the first month, but remained at a highly motivating level for the patient after 6 months.

    DISCUSSION: The study suggests that tRNS may be an effective treatment for some cases of neuropathic pain. An important result was the indication that even low levels of stimulation may have substantial effects.

  • 43.
    Almberg, Maria
    et al.
    Mobility Centre Gothenburg, Sweden.
    Selander, Helena
    Mobility Centre Gothenburg, Sweden.
    Falkmer, Marita
    Jönköping University, School of Education and Communication, HLK, CHILD. School of Occupational Therapy and Social Work, Faculty of Health Sciences, Curtin University, Perth, Australia.
    Vaz, Sharmila
    School of Occupational Therapy and Social Work, Faculty of Health Sciences, Curtin University, Perth, Australia.
    Ciccarelli, Marina
    School of Occupational Therapy and Social Work, Faculty of Health Sciences, Curtin University, Perth, Australia.
    Falkmer, Torbjörn
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Rehabilitation. Jönköping University, School of Health and Welfare, HHJ. CHILD. School of Occupational Therapy and Social Work, Faculty of Health Sciences, Curtin University, Perth, Australia.
    Experiences of facilitators or barriers in driving education from learner and novice drivers with ADHD or ASD and their driving instructors2017In: Developmental Neurorehabilitation, ISSN 1751-8423, E-ISSN 1751-8431, Vol. 20, no 2, 59-67 p.Article in journal (Refereed)
    Abstract [en]

    Background: Little is known about whether individuals with autism spectrum disorder (ASD) or attention deficit hyperactive disorder (ADHD) experience any specific facilitators or barriers to driving education.

    Objective: To explore the facilitators or barriers to driving education experienced by individuals with ASD or ADHD who obtained a learner’s permit, from the perspective of the learner drivers and their driving instructors.

    Methods: Data were collected from 33 participants with ASD or ADHD, and nine of their driving instructors.

    Results: Participants with ASD required twice as many driving lessons and more on-road tests than those with ADHD. Participants with ADHD repeated the written tests more than those with ASD. Driving license theory was more challenging for individuals with ADHD, whilst individuals with ASD found translating theory into practice and adjusting to “unfamiliar” driving situations to be the greatest challenges.

    Conclusion: Obtaining a driving license was associated with stressful training experience.

  • 44. Alping, P.
    et al.
    Islam-Jakobsson, Protik
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Novakova, L.
    Salzer, Jonatan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Björck, A.
    Axelsson, M.
    Malmeström, C.
    Fink, K.
    Frisell, T.
    Lycke, J.
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Piehl, F.
    Superior efficacy and tolerability of rituximab as compared to fingolimod for MS patients switching from natalizumab due to positive JC virus serology2015In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 21, no 11, 555-555 p., P1079Article in journal (Other academic)
  • 45.
    Alping, P.
    et al.
    Danderyd Hosp, Karolinska Inst, Clin Neurosci, Stockholm, Sweden..
    Svenningsson, A.
    Danderyd Hosp, Karolinska Inst, Clin Sci, Stockholm, Sweden..
    Salzer, J.
    Umea Univ, Pharmacol & Clin Neurosci, Umea, Sweden..
    Burman, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Uppsala Univ, Neurosci, Uppsala, Sweden..
    Dahle, C.
    Linkoping Univ, Clin & Expt Med, Linkopin, Sweden..
    Fink, K.
    Danderyd Hosp, Karolinska Inst, Clin Neurosci, Stockholm, Sweden..
    Hillert, J.
    Danderyd Hosp, Karolinska Inst, Clin Neurosci, Stockholm, Sweden..
    Lycke, J.
    Univ Gothenburg, Clin Neurosci & Rehabil, Gothenburg, Sweden..
    Landtblom, A-M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Martin, C.
    Danderyd Hosp, Karolinska Inst, Clin Sci, Stockholm, Sweden..
    Nilsson, P.
    Lund Univ, Neurol, Lund, Sweden..
    Walentin, F.
    Orebro Univ Hosp, Neurol, Orebro, Sweden..
    Olsson, T.
    Danderyd Hosp, Karolinska Inst, Clin Neurosci, Stockholm, Sweden..
    Frisell, T.
    Karolinska Inst, Med Solna, Stockholm, Sweden..
    Piehl, F.
    Danderyd Hosp, Karolinska Inst, Clin Neurosci, Stockholm, Sweden..
    Rituximab in multiple sclerosis; data from the swedish MS registry.2016In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 22, no suppl. 3, 49-49 p.Article in journal (Refereed)
  • 46. Alping, Peter
    et al.
    Frisell, Thomas
    Novakova, Lenka
    Islam-Jakobsson, Protik
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Salzer, Jonatan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Björck, Anna
    Axelsson, Markus
    Malmeström, Clas
    Fink, Katharina
    Lycke, Jan
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Piehl, Fredrik
    Rituximab versus Fingolimod after Natalizumab in Multiple Sclerosis Patients2016In: Annals of Neurology, ISSN 0364-5134, E-ISSN 1531-8249, Vol. 79, no 6, 950-958 p.Article in journal (Refereed)
    Abstract [en]

    Objective: Many JC virus antibody-positive relapsing-remitting multiple sclerosis (RRMS) patients who are stable on natalizumab switch to other therapies to avoid progressive multifocal leukoencephalopathy.

    Methods: We compared outcomes for all RRMS patients switching from natalizumab due to JC virus antibody positivity at 3 Swedish multiple sclerosis centers with different preferential use of rituximab and fingolimod (Stockholm, n = 156, fingolimod 51%; Gothenburg, n = 64, fingolimod 88%; Umea, n = 36, fingolimod 19%), yielding a total cohort of N = 256 (fingolimod 55%).

    Results: Within 1.5 years of cessation of natalizumab, 1.8% (rituximab) and 17.6% (fingolimod) of patients experienced a clinical relapse (hazard ratio for rituximab = 0.10, 95% confidence interval [CI] = 0.02-0.43). The hazard ratio (favoring rituximab) for adverse events (5.3% vs 21.1%) and treatment discontinuation (1.8% vs 28.2%) were 0.25 (95% CI = 0.10-0.59) and 0.07 (95% CI = 0.02-0.30), respectively. Furthermore, contrast-enhancing lesions were found in 1.4% (rituximab) versus 24.2% (fingolimod) of magnetic resonance imaging examinations (odds ratio = 0.05, 95% CI = 0.00-0.22). Differences remained when adjusting for possible confounders (age, sex, disability status, time on natalizumab, washout time, follow-up time, and study center).

    Interpretation: Our findings suggest an improved effectiveness and tolerability of rituximab compared with fingolimod in stable RRMS patients who switch from natalizumab due to JC virus antibody positivity. Although residual confounding factors cannot be ruled out, the shared reason for switching from natalizumab and the preferential use of either rituximab or fingolimod in 2 of the centers mitigates these concerns.

  • 47.
    Alsiö, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Rask-Andersen, Mathias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Chavan, Rohit A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Olszewski, Pawel K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Levine, Allen S.
    Fredriksson, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Exposure to a high-fat high-sugar diet causes strong up-regulation of proopiomelanocortin and differentially affects dopamine D1 and D2 receptor gene expression in the brainstem of rats2014In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 559, 18-23 p.Article in journal (Refereed)
    Abstract [en]

    A strong link between obesity and dopamine (DA) has been established by studies associating body weight status to variants of genes related to DA signalling. Human and animal studies investigating this relationship have so far focused mainly on the role of DA within the mesolimbic pathway. The aim of this study was to investigate potential DA receptor dysregulation in the brainstem, where these receptors play a potential role in meal termination, during high-fat high-sugar diet (HFHS) exposure. Expression of other key genes, including proopiomelanocortin (POMC), was also analyzed. We randomized rats into three groups; ad libitum access to HFHS (n=24), restricted HFHS access (n=10), or controls (chow-fed, n=10). After 5 weeks, brainstem gene expression was investigated by qRT-PCR. We observed an increase in POMC expression in ad libitum HFHS-fed rats compared to chow-fed controls (p<0.05). Further, expression of DA D2 receptor mRNA was down-regulated in the brainstem of the HFHS ad libitum-fed rats (p<0.05), whereas expression of the DA D1 receptor was upregulated (p<0.05) in these animals compared to chow-fed rats. In control experiments, we observed no effect relative to chow-fed controls on DA-receptor or POMC gene expression in the hypothalamus of HFHS diet-exposed rats, or in the brainstem of acutely food deprived rats. The present findings suggest brainstem POMC to be responsive to palatable foods, and that DA dysregulation after access to energy-dense diets occurs not only in striatal regions, but also in the brainstem, which could be relevant for overeating and for the development and maintenance of obesity.

  • 48.
    Alstermark, Bror
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Ekerot, Carl-Fredrik
    The lateral reticular nucleus: integration of descending and ascending systems regulating voluntary forelimb movements2015In: Frontiers in Computational Neuroscience, ISSN 1662-5188, Vol. 9, 102Article in journal (Refereed)
    Abstract [en]

    Cerebellar control of movements is dependent on mossy fiber input conveying information about sensory and premotor activity in the spinal cord. While much is known about spino-cerebellar systems, which provide the cerebellum with detailed sensory information, much less is known about systems conveying motor information. Individual motoneurones do not have projections to spino-cerebellar neurons. Instead, the fastest route is from last order spinal interneurons. In order to identify the networks that convey ascending premotor information from last order interneurons, we have focused on the lateral reticular nucleus (LRN), which provides the major mossy fiber input to cerebellum from spinal interneuronal systems. Three spinal ascending systems to the LRN have been investigated: the C3-C4 propriospinal neurones (PNs), the ipsilateral forelimb tract (iFT) and the bilateral ventral flexor reflex tract (bVFRT). Voluntary forelimb movements involve reaching and grasping together with necessary postural adjustments and each of these three interneuronal systems likely contribute to specific aspects of forelimb motor control. It has been demonstrated that the command for reaching can be mediated via C3-C4 PNs, while the command for grasping is conveyed via segmental interneurons in the forelimb segments. Our results reveal convergence of ascending projections from all three interneuronal systems in the LRN, producing distinct combinations of excitation and inhibition. We have also identified a separate descending control of LRN neurons exerted via a subgroup of cortico-reticular neurones. The LRN projections to the deep cerebellar nuclei exert a direct excitatory effect on descending motor pathways via the reticulospinal, vestibulospinal, and other supraspinal tracts, and might play a key role in cerebellar motor control. Our results support the hypothesis that the LRN provides the cerebellum with highly integrated information, enabling cerebellar control of complex forelimb movements.

  • 49.
    Alstermark, Bror
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Hultborn, H
    University of Copenhagen Department of Neuroscience and Pharmacology Copenhagen N. Denmark.
    Jankowska, E
    Sahlgrenska Academy, University of Gothenburg Department of Physiology Gothenburg Sweden.
    Pettersson, L-G
    Sahlgrenska Academy, University of Gothenburg Department of Physiology Gothenburg Sweden.
    Anders Lundberg (1920-2009).2010In: Experimental Brain Research, ISSN 0014-4819, E-ISSN 1432-1106, Vol. 200, no 3-4, 193-195 p.Article in journal (Other (popular science, discussion, etc.))
    Abstract [en]

    Anders Lundberg was one of the founding editorial board members for EBR when it began its life in 1976 under the editorship of John Eccles. He was also one of the most prolific contributors to the journal with a total of 49 papers, including a series of 16 on the topic of “integration in descending motor pathways controlling the forelimb in the cat”. He continued as an editor of the journal until volume 16 when he persuaded his younger colleague Hans Hultborn to take his place. Hans is one of the authors of the obituary. –John Rothwell

  • 50.
    Althini, Susanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Experimental Studies of BMP Signalling in Neuronal Cells2003Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The developing nervous system depends largely on extracellular cues to shape its complex network of neurons. Classically, neurotrophins are known to be important mediators in this process. More recently, Bone Morphogenetic Proteins (BMPs), belonging to the Transforming Growth Factor beta (TGFβ) superfamily of secreted cytokines, have been shown to exert a wide range of effects, such as cellular growth, differentiation, survival and apoptosis, both in the developing and adult nervous system. They signal via serine/threonine kinase receptor essentially to the Smad pathway, which carries the signal to the nucleus where the transcription of target genes is regulated.

    This thesis investigates the functions of BMPs in the nervous system, using a set of different models. Firstly, a targeted deletion of GDF10 (BMP3b) in the mouse was established to evaluate the role of this growth/differentiation factor in the hippocampal formation, a brain area known to be involved in memory processing. Other members of the TGFβ superfamily likely compensate for the lack of GDF10, since no detectable alterations in hippocampal function or gene transcription profile have been found. Secondly, a mouse model was set up, with the aim to study impaired BMP-signalling in dopaminergic neurons. The tyrosine hydroxylase (TH) locus was used to drive the expression of dominant negative BMP receptors by means of bicistronic mRNAs. TH is the rate-limiting enzyme in the biosynthesis of catecholamine and the mice described, show a graded decrease of TH-activity resulting in severe to mild dopamine deficiency. The contribution of the dominant negative BMP receptors to the phenotype is however secondary to the apparent TH hypomorphism. The final theme of this thesis is the potentiating effects of BMPs on neurotrophin-induced neurite outgrowth as studied in explanted ganglia from chick embryos and in the rat phaeochromocytoma cell line PC12. A number of pharmacological inhibitors of intracellular signalling kinases were applied to the cultures in order to reveal the contribution of different pathways to the enhanced neurite outgrowth. We made the unexpected finding that inhibition of MEK signalling mimicked the potentiating effects of BMP stimulation in the chick system. The underlying mechanisms for the synergistic effects, however, are still an enigma.

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