Involvement of the alpha-7 nicotinic receptor (±7nAChR) of the hippocampus and prefrontal cortex in the behavioral and plastic responses resulting from the consumption of a high-fat diet

• Grant number: 22/08010-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: August 01, 2022
• End date: May 31, 2026
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Licio Augusto Velloso
• Grantee: Gabriela Pandini Silote
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
• Associated research grant: 13/07607-8 - OCRC - Obesity and Comorbidities Research Center, AP.CEPID

Abstract

Obesity and depressive disorder are considered serious health problems that have high prevalence and morbidity and mortality rates. Obesity is associated with increased prevalence and severity of the depressive disorder, and this association occurs in a bidirectional manner. However, the molecular mechanisms involved in the association of depression with obesity have not been elucidated. Interestingly, evidence points out that immune and inflammatory aspects are involved in both conditions. Several studies show an increase in plasma levels of pro-inflammatory cytokines such as interleukin 6 (IL-6), interleukin 1 beta (IL-1²), tumor necrosis factor-alpha (TNF-±) and increased activation of microglia that may contribute to the worsening of the inflammatory response at the central level in obesity and depression. The cholinergic system plays an important role in inflammation. Notably, in both pathologies, there is a deficit in the anti-inflammatory response mediated by the alpha-7 nicotinic receptor (±7nAChR). Previous studies revealed that the high-fat diet (HFD) increased the expression of pro-inflammatory mediators in the hypothalamus, promoted the accumulation of microglia and astrocytes, and reduced the expression of the ±7nAChR receptor in the same brain region after three days of high-fat diet consumption. However, no studies have investigated the involvement of the ±7nAChR receptor modulatory response in depressive disorder associated with high-fat diet consumption. Our objective will be to investigate the participation of the ±7nAChR receptor located in the hippocampus (HPC) and prefrontal cortex (PFC) in behavioral, metabolic, endocrine, inflammatory and plastic alterations induced by the consumption of a high-fat diet. (AU)