EVALUATION OF THE EFFECT OF HYPOXIA ON THE ACTIVATION OF PATHWAYS RELATED TO THE CONTROL OF AGING IN PROOPIOMELANOCORTIN NEURONS OF THE HYPOTHALAMUS

• Grant number: 24/01959-4
• Support Opportunities: Scholarships in Brazil - Master
• Start date: July 01, 2024
• End date: February 28, 2026
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Licio Augusto Velloso
• Grantee: Carolina Namie Sato Cortezão
• 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

Abstract

Proopiomelanocortin (POMC) neurons of the hypothalamus are important componentsof a neural circuit that regulates aging. Previous studies have demonstrated that theactivity of the inflammatory transcription factor, NFk NFk², in POMC neurons of thehypothalamus activates systemic pathways that accelerate the aging process. Instudies that characterized this phenomenon, genetic interventions were used toactivate or inactivate NFk NFk²; dietary intervention with increased consumption of fattyacids, were also used as an intervention to activate inflammatory signaling in thehypothalamus. During aging, there is a progressive reduction in cerebral blood flow,resulting in a decline in neuronal oxygenation. Howe ver, it is not known whetherexposure to a hypoxic environment can contribute to accelerating the aging process. Inthis exploratory project we will use a cell line of POMC neurons to evaluate the impactof exposure to hypoxia on the activation of NFk NFk² and other components of the cellularpathway that regulates aging. To this end, in the first stage of the study POMC neuronsin culture will be exposed to an oxygen gradient ranging from 20% to 3%. NFk NFk² activitywill then be measured by Elisa and the highest oxygen concentration that results inNFkNFk² activation will be used in subsequent experiments. In the second part of thestudy, we will evaluate the expression of genes responsive to NFk NFk², such as IL1 IL1²,TNFTNF± and IL 6. The expression of TGF TGF² and RNA granules, both components of thesignaling pathway that promotes aging, will also be measured. Finally, we will evaluatethe structure and function of mitochondria through fluorescence microscopy, labelingwith Mito tracker , and determination of oxygen consumption u sing the Seahorseequipment. We believe that the study could help advance the understanding of themechanisms involved in the regulation of the aging process by POMC neurons in thehypothalamus.