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Evaluation of the medial prefrontal cortex interhemispheric connections in the resilience and susceptibility to the social defeat stress: because the side matters

Grant number: 20/15216-2
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): May 01, 2021
Effective date (End): April 30, 2023
Field of knowledge:Biological Sciences - Pharmacology - Neuropsychopharmacology
Principal researcher:Ricardo Luiz Nunes de Souza
Grantee:Gessynger Morais Silva
Home Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Although the known association between stress and the development of psychiatric diseases, not every individual who has experienced adversities develops such diseases. This is related to individual characteristics, which determine how each individual cope and adapts to adversity, leading up to its resilience or susceptibility to the stress. The great prevalence of such diseases, together with the low efficacy and high rates of adverse effects of the currently available pharmacological therapy, make the understanding of the mechanisms related to this resilience and susceptibility important to the discovery of new therapeutical targets. In this sense, the functional lateralization of the medial prefrontal cortex (mPFC) and its alterations related to the chronic stress exposure has gained attention in recent years. Results suggest that the chronic stress induces long-lasting alterations in the mPFC, decreasing left mPFC (LmPFC) activity and increasing right mPFC (RmPFC) activity, resulting in the behavioral alterations found in stress susceptible individuals. Considering the wide interhemispheric connection and the inhibitory tone between the LmPFC and the RmPFC, our hypothesis is that alterations in the activity of such projections during stressful situations is related to the stress susceptibility. To test this hypothesis, the aim of this work is to evaluate the effects of the chemogenetic manipulation of the interhemispheric projections of the mPFC in an animal model of psychosocial stress, in addition to characterize morphologically these projections in female and male mice, since the increased female susceptibility to the development of mood disorders is well described.

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