Stress-induced epigenetic alterations in early life on infralimbic mineralocorticoid modulation in adult-challenged rats: influences on late anxiety-like behavior and extinction memory

• Grant number: 21/14690-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: March 01, 2023
• End date: February 28, 2026
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Carolina Demarchi Munhoz
• Grantee: Kairo Alan Albernaz Mariano
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Stress is a fundamental condition for survival. It concerns the ability to respond physiologically and behaviorally to events that threaten the physical and emotional integrity of the organism. Added to stress, anxiety and the ability to store information as memories constitute a basic set of abilities of several animal species, including humans. Individuals deal with aversive situations and return to a normal lifestyle when adversity ends. Nevertheless, in certain circumstances, traumas caused by high-stress levels can be preceded by increased anxiety and memory distortions in stress-related disorders, inducing an exhaustion process that makes individuals susceptible to them. Early-life stress is a fundamental cause of behavioral changes and epigenetic alterations that influence adulthood, especially when are linked to the hypothalamus-pituitary-adrenal glands axis alterations, formed by structures responsive and responsible for a stressor's response. The HPA axis releases glucocorticoids during stress, targeting mineralocorticoid (MR) and glucocorticoid (GR) receptors. These receptors act as transcription factors in the rapid neuronal excitability responses associated with stress and in the formation and maintenance of aversive memories. MR and GR are present in essential regions related to cognition, emotions, and early stress processing, such as the medial prefrontal cortex (mPFC). However, while most studies attempt to elucidate the stress-induced deleterious actions of glucocorticoids via GR, the objective of this project is to understand how early life epigenetic alterations influence stress, anxiety, and memory in adulthood and how MR of the mPFC is inserted in this context.