Histological changes associated with neuroimmune-metabolic interactions in the hypothalamus

• Grant number: 25/11576-8
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2025
• End date: October 31, 2026
• Field of knowledge: Biological Sciences - Biology
• Principal Investigator: Natália Ferreira Mendes
• Grantee: Natália Ferreira Mendes
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• City of the host institution: Campinas
• 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
• Associated scholarship(s): 25/25342-9 - Impact of a high-fat diet on CXCR4 expression in hypothalamic tanycytes, BP.IC; 25/25369-4 - Histological analysis of alterations induced by a maternal high-fat diet in adult CCR2-knockout offspring., BP.IC

Abstract

The hypothalamus plays a central role in regulating energy homeostasis, integrating central and peripheral signals, such as hormones and neurotransmitters, to adjust neural responses that control feeding behavior and metabolism. Among the cellular components of this region, tanycytes stand out as specialized glial cells located along the wall of the third ventricle. These cells contribute to neurogenesis and to the maintenance of neural circuits involved in physiological functions essential for survival. Evidence indicates that adverse stimuli during intrauterine development can cause long-lasting changes in the structure and function of the central nervous system, particularly affecting the hypothalamic neuronal network and predisposing offspring to metabolic disorders. Over the past decade, adult hypothalamic neurogenesis and the effects of fetal programming on metabolism have been widely studied. However, the role of chemokine receptors and the involvement of immune cells in these processes remain poorly understood. In this context, this proposal encompasses two research projects. The first aim is to characterize the presence of CCR2-positive myeloid cells in the hypothalamus of adult offspring from CCR2-knockout mice, using a model of metabolic programming induced by a high-fat diet. Morphological changes in key tissues involved in the regulation of energy balance in these offspring will also be analyzed. The second project will assess the expression and distribution of the CXCR4 receptor in tanycytes, exploring its modulation by a high-fat diet and its potential involvement in hypothalamic neurogenesis. The expected results may expand our knowledge about the mechanisms by which diet influences neuronal plasticity and the recruitment of immune cells in the brain, contributing to the development of new therapeutic approaches for metabolic and neuroendocrine disorders. (AU)