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Ghrelin restores memory impairment following olfactory bulbectomy in mice by activating hippocampal NMDA1 and MAPK1 gene expression
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Univ Nacl Cordoba, CONICET, Inst Invest Ciencias Salud INICSA, Inst Fisiol Humana, Santa Rosa 1085, X5000ESU, Cordoba, Argentina.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Univ Nacl Cordoba, CONICET, Inst Invest Ciencias Salud INICSA, Inst Fisiol Humana, Santa Rosa 1085, X5000ESU, Cordoba, Argentina; Univ Nacl Cordoba, Fac Ciencias Med, Santa Rosa 1085, X5000ESU, Cordoba, Argentina.ORCID iD: 0000-0002-4346-9883
Univ Nacl Cordoba, Fac Ciencias Quim, IFEC, Dept Farmacol, CONICET, Av Haya Torre & Medina Allende, Cordoba, Argentina.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
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2021 (English)In: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 410, article id 113341Article in journal (Refereed) Published
Abstract [en]

Ghrelin (Ghrl) is an orexigenic peptide with potential roles in the modulation of anxiety- and depressive-like symptoms induced by bilateral olfactory bulbectomy (OB) in rodents. In the present work, we assessed whether intrahippocampal Ghrl could reverse OB-induced depressive-like and amnesic effects by regulating molecular mechanisms related to neuroplasticity. Adult female albino Swiss mice were divided into sham and OB groups, and infused with saline (S) or Ghrl 0.03 nmol/μl, 0.3 nmol/μl, or 3 nmol/μl into the hippocampus before exposition to open-field test (OFT) and tail suspension test (TST) or immediately after training in the object recognition test (ORT). After test phase in ORT, animals were euthanized and their hippocampi were dissected to study the expression of genes related to memory. The OB-S animals presented hyperlocomotion in OFT, increased immobility in TST and memory impairment compared to sham-S (p < 0.05), but acute intrahippocampal infusion of Ghrl 0.3 nmol/μl produced an improvement on these parameters in OB animals (p < 0.05). In addition, this dose of Ghrl reversed OB-induced low expression of NMDA1 and MAPK1 iso1 and up-regulated the expression of CaMKIIa iso1 and iso2, and MAPK1 iso2 (p < 0.05). These results extend the existing literature regarding OB-induced behavioral and neurochemical changes, and provide mechanisms that could underlie the antidepressant effect of Ghrl in this model.

Place, publisher, year, edition, pages
Springer Nature, 2021. Vol. 410, article id 113341
Keywords [en]
Ghrelin, Olfactory bulbectomy, Depression, Object recognition memory, NMDA, MAPK, ERK2
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:uu:diva-449003DOI: 10.1016/j.bbr.2021.113341ISI: 000663471200013PubMedID: 33964353OAI: oai:DiVA.org:uu-449003DiVA, id: diva2:1591493
Funder
Swedish Research CouncilThe Swedish Brain FoundationAvailable from: 2021-09-06 Created: 2021-09-06 Last updated: 2024-01-15Bibliographically approved

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Poretti, María BelénRodríguez, Pamela ElizabethSchiöth, Helgi B.Carlini, Valeria Paola
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