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Characterization of the molecular mechanisms that regulate adult neurogenesis in the hypothalamus in response to reproductive stimulus

Grant number: 21/07288-6
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): August 01, 2021
Effective date (End): July 31, 2023
Field of knowledge:Biological Sciences - Physiology - General Physiology
Principal researcher:Licio Augusto Velloso
Grantee:Ariane Maria Zanesco
Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:13/07607-8 - OCRC - Obesity and Comorbidities Research Center, AP.CEPID

Abstract

Adult neurogenesis in the hypothalamus is known to renew subpopulations of neurons that play central roles in controlling energy homeostasis. Still incipient studies suggest that stimuli with reproductive hormones also induce neurogenesis in the hypothalamus, potentially generating neurons that play an important role in preserving reproductive capacity. Recent studies indicate that BDNF is an important mediator in the process of hypothalamic neurogenesis in response to regulatory signals of energy homeostasis. Using bioinformatics to evaluate hypothalamic neurons that express BDNF, we identified the subpopulations FezF1 and Kiss1. Kiss1 neurons are important for reproductive function, however FezF1 neurons have virtually unknown function. Based on these data, we hypothesized that reproductive stimuli can activate the expression of BDNF in these subpopulations of neurons generating a neurogenesis inducing signal that aims to renew neurons with a regulatory function of reproduction. To test this hypothesis, we will use reporter mice for Kiss1 and FezF1 and evaluate BDNF production after different types of stimuli representative of reproductive activity. In the second part of the study, we will use FezF1-cre and Kiss1-cre mice to inhibit BDNF expression in each of these subpopulations; then we will assess the impact of the respective inhibitions on neurogenesis induced by representative stimuli of reproductive activity. This study can lead to advances on understanding the hypothalamic mechanisms that regulate reproduction and how these phenomena are preserved throughout life. (AU)

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