Evaluation of the CXCR4 receptor's role in adult hypothalamic neurogenesis

• Grant number: 25/00121-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: March 01, 2025
• End date: February 28, 2027
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Natália Ferreira Mendes
• Grantee: Igor Vinicius Sousa Cavalheiro
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 22/06282-7 - Involvement of CXCL12/CXCR4 pathway in monocyte chemotaxis and postnatal neurogenesis during hypothalamic inflammation and of maternal obesity in monocyte sexual dimorphism., AP.GR

Abstract

By integrating signals from both central and peripheral sources, the hypothalamus plays a crucial role in maintaining homeostasis. This regulation is finely tuned, ensuring that the organism responds appropriately to the environmental and physiological adaptations necessary for species evolution. As a protective mechanism, neurogenesis in the hypothalamus continues into adulthood, responding to various stimuli such as neurotrophic factors, hormones, nutrients, and chemokine signaling. Neural stem cells, located in the third ventricle and the subventricular zone, have the ability to differentiate into different types of neurons and glial cells. The newly formed neurons and cells migrate to their designated areas, integrating into existing neural networks and parenchymal cells. From published single-cell sequencing data, we found that both the arcuate nucleus of the hypothalamus and the median eminence express the chemokine receptor CXCR4 in tanycytes, specialized glial cells that play a critical role in regulating neurogenesis and communicating with neural stem cells. In the hippocampus, it has been shown that the interaction between CXCL12 and CXCR4 leads to the recruitment of neural stem cells, promoting their migration and differentiation into neurons. However, the role of CXCR4 in hypothalamic neurogenesis has not yet been explored. In this project, we will investigate whether the expression of CXCR4 in the hypothalamus is influenced by diet and/or sex and analyze the effects of removing this receptor from tanycytes on cell proliferation, survival and differentiation, as well as its potential impact on energy balance. The results may uncover a new signaling pathway involved in the regulation of hypothalamic neurogenesis, providing fresh insights into the mechanisms controlling energy homeostasis and hypothalamic neuronal plasticity.