Role of vasopressin neurons from the supraoptic nucleus in controlling the activity of hypothalamic paraventricular corticotropin-releasing hormone neurons in fasted and refed mice.

• Grant number: 23/12497-9
• Support Opportunities: Scholarships in Brazil - Master
• Start date: May 01, 2024
• End date: April 30, 2026
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Rodrigo César Rorato
• Grantee: Ana Paula Neves Brianezi
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

The hypothalamic-pituitary-adrenal (HPA) axis is associated with the control of energy homeostasis. Corticotropin-releasing hormone neurons situated in the paraventricular nucleus of the hypothalamus (CRHPVN), the major HPA axis regulator, are known to coordinate metabolism via endocrine, autonomic and behavioral responses after stressful stimuli, such as food deprivation. The HPA axis can be activated through metabolic stress induced by fasting. In addition, recent studies have suggested that changes in plasma hormones levels related to metabolic states, such as leptin and insulin, may be involved in fasting-induced HPA axis activation. Furthermore, it has been described that CRHPVN neurons receive inputs from different brain sites which can sense changes in peripheral energy stores, such as the supraoptic (SON) nucleus. Hence, the present study proposes to investigate the role of SON arginine-vasopressin (AVPSON) expressing neurons projection to CRFPVN neurons and its implication in food intake responses of animals submitted to fasting or fasting and refeeding. Thereby, genetically modified animals associated with viral vectors carrying the genetic sequence for the expression of muscarinic mutant receptors (DREADDs) will allow us to modulate OTSON neuronal activity of fasted and refed animals. The understanding of the AVPSON - CRFPVN connection dynamic may elucidate the pathways/mechanisms involved in the modulation of the HPA axis activity during metabolic stress and provide scientific data for possible future therapies for the control of metabolic diseases, such as obesity and diabetes.