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

• Grant number: 21/07288-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: August 01, 2021
• End date: July 31, 2025
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Licio Augusto Velloso
• Grantee: Ariane Maria Zanesco
• Host 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
• Associated scholarship(s): 24/03519-1 - The effects of BDNF production by Kiss1 neurons in adult hypothalamic neurogenesis, BE.EP.DR

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)