Effect of acute restraint stress on mitochondrial function and its repercussions on late anxiety-like behaviors and extinction of aversive memory in adult male and female rats subjected to maternal separation

• Grant number: 23/13386-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): September 01, 2024
• Effective date (End): April 30, 2027
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Carolina Demarchi Munhoz
• Grantee: Robbert Mota Pereira
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Throughout life, it is inevitable to experience stressful situations; in some cases, brain structures such as the hypothalamus, amygdala, and hippocampus (HP) are affected, which can trigger or worsen anxiety disorders and impair memory processing and learning. Glucocorticoid hormones (GCs), released by activation of the hypothalamic-pituitary-adrenal axis (HPA axis), are the main mediators of the stress response, coordinating both acute and late responses. GCs are important for cognition, emotions, and initial stress processing, in addition to modulating mitochondrial function, essential for maintaining physiological balance. When stress occurs early in life, mediated by the absence of maternal care, proper nutrition, and low temperatures, it can predispose the individual throughout their life, especially since the HPA axis is still developing. Literature has indicated that during a stressful event, impaired stress responsiveness can impact mitochondrial function, altering the density of Ca2+ and K+ ion channels and the dynamics between mitochondrial fusion and fission. Although studies focus on investigating the acute and late effects of GCs on brain structures, little is known about the repercussions of early-life stress on hippocampal mitochondrial function in adulthood. The objective of this study is to assess the impact of early-life stress caused by maternal separation on the late effects of acute restraint stress in adulthood in male and female rats. To achieve this, we will evaluate mitochondrial function and oxidative stress in the hippocampus, late anxiety-like behavior, and aversive memory extinction. In this project, we aim to understand how a stress-free early life affects the ability to cope with stress in adulthood, considering mitochondria as a biomarker. This can provide important tools for lifelong health promotion strategies.