Behavioral effects of direct in vivo reprogramming of reactive glial cells into interneurons in the medial prefrontal cortex

• Grant number: 21/13515-5
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: March 14, 2022
• End date: September 13, 2022
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Alline Cristina de Campos
• Grantee: Franciele Franco Scarante
• Supervisor: Benedikt A. Berninger
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: King's College London, England
• Associated to the scholarship: 19/09178-3 - Involvement of endocannabinoid signaling and neuroplasticity within the prefrontal cortex in the behavioral effects of the combination cannabidiol and escitalpram in stressed mice, BP.DR

Abstract

The medial prefrontal cortex (mPFC) participates in the neurobiology of stress responses and in the pathophysiology of anxiety- and depression-like phenotypes. The activity of GABAergic interneurons modulates mPFC function and controls the behavioral responses coordinated by this brain region. Interestingly, reactive glial cells, particularly NG2 glial cells, are a potential source of new GABAergic interneurons in the adult brain. Recently, studies have introduced the possibility of directly reprogramming reactive glial cells into GABAergic interneurons in vivo by inducing the expression of transcription factors via a retroviral vector that stably transfects proliferative cells only. Being NG2 glial cells the main proliferative cells in most brain regions, the injection of these retroviral vectors will target mainly this cell type. Therefore, the goal of this project is to evaluate the behavioral effects of the direct in vivo reprogramming of reactive glial cells into GABAergic interneurons in the mPFC of mice. We will use C57Bl/6J male mice that will receive the intra-mPFC injection of the retroviral vectors that induce glia-to-interneuron reprogramming. Six-to-eight weeks later, mice will be submitted to tasks to evaluate anxiety- and depression-like behaviors. We will use the behavioral tasks novelty suppressed feeding and tail suspension test. The glial-to-interneuron reprogramming efficacy will be confirmed labeling transfected cells with interneuron molecular markers through immunohistochemistry. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

GALANTE, CHIARA; MARICHAL, NICOLAS; SCARANTE, FRANCIELE FRANCO; GHAYAD, LITSA MARIA; SHI, YOURAN; SCHUURMANS, CAROL; BERNINGER, BENEDIKT; PERON, SOPHIE. Enhanced proliferation of oligodendrocyte progenitor cells following retrovirus mediated Achaete-scute complex-like 1 overexpression in the postnatal cerebral cortex in vivo. FRONTIERS IN NEUROSCIENCE, v. 16, p. 14-pg., 2022-12-02. (21/13515-5)