The role of the a7nAChR receptor in preventing the activation of the ceramide pathway

• Grant number: 24/21772-6
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: May 01, 2025
• End date: July 31, 2025
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Marcio Alberto Torsoni
• Grantee: Melissa Santos de Aguiar
• Supervisor: Herve Le Stunff
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
• Institution abroad: Institut Des Neurosciences Paris-Saclay, France
• Associated to the scholarship: 23/11551-0 - Effects of acute exposure to high-fat diet on epigenetic control that may modulate ±7nAchR receptor expression in hypothalamic cells., BP.IC

Abstract

The hypothalamus is one of the main regulatory centers for energy homeostasis and this control is profoundly impaired by inflammatory processes that damage hypothalamic signaling, which can result in the development of metabolic disorders. The lipid species that accumulate under these conditions, such as ceramides or their metabolites, are among the most detailed because they can lead to neuroinflammation and dysregulation of energy metabolism. The ¿7nAchR is expressed in the central nervous system and recent studies have demonstrated the ability of these receptors to activate signal transduction pathways that result in the inhibition of the transcription of pro-inflammatory cytokines and modulate energy homeostasis. We recently demonstrated that the consumption of a high-fat diet (DH) for three days was able to reduce the hypothalamic expression of the ¿7nAChR receptor and make the hypothalamus more susceptible to inflammatory damage. On the other hand, the selective receptor agonist impairs the power of the inflammatory response. These results demonstrated that the inflammatory process induced by LPS or HFD can reduce the expression of ¿7nAChR, early on, and making the cell or cellular environment more permissive to another inflammatory process. In this context, we investigated and understood the role of the ¿7nAChR receptor in preventing the activation of the ceramide pathway. To this end, expand our knowledge in ¿7nAChR research and bring new methodological approaches to contribute to the development and improvement of techniques that will add to our scientific and academic environment. Innovative techniques will be imported and improved, such as the method for quantifying ceramides using diacylglycerol kinase