Impact of chronic stress in adolescence on neural circuits and regulation of the HPA axis: role of signaling via glucocorticoid receptor

• Grant number: 25/26220-4
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: September 01, 2026
• End date: December 31, 2030
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Carolina Demarchi Munhoz
• Grantee: Gabriela Esteves Sbardellotto
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Adolescence represents a critical neurodevelopmental window characterized by intense synaptic plasticity and functional remodeling of corticolimbic circuits involved in emotional, cognitive, and neuroendocrine regulation. During this period, the proper integration between the medial prefrontal cortex, hippocampus, amygdala, and the hypothalamic-pituitary-adrenal (HPA) axis is essential for the establishment of adaptive stress responses in adulthood. Increasing evidence indicates that chronic stress exposure during adolescence may disrupt this maturational process, leading to persistent alterations in glucocorticoid receptor (GR)-dependent plasticity, corticolimbic circuit activity, and neuroendocrine responsiveness. However, the mechanisms through which these long-lasting alterations become established throughout development remain poorly understood. Therefore, the present project aims to investigate how stress exposure during adolescence interferes with the functional maturation of medial prefrontal cortex-basolateral amygdala and medial prefrontal cortex-dorsal hippocampus circuits, as well as with glucocorticoid signaling-dependent mechanisms associated with vulnerability or resilience to stress in adulthood. To address this question, the study will integrate behavioral, neuroendocrine, and neurobiological analyses in male and female rats, seeking to identify sex-dependent mechanisms potentially involved in the development of stress-related psychiatric disorders, including anxiety, depression, and post-traumatic stress disorder (PTSD). (AU)