Experimental posttraumatic stress disorder: the influence of early life stress and characterization of neural circuits

Author(s)

Nayara Cobra Barreiro Barroca

• Document type: Master's Dissertation
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC)
• Defense date: 2020-03-25

Examining board members

Norberto Garcia Cairasco; Nayanne Beckmann Bosaipo; Cláudia Maria Gaspardo

• Advisor: Norberto Garcia Cairasco

Abstract

Early life stress (ELS) situations such as physical, sexual and emotional abuse or neglect are associated with a higher risk of developing psychopathology in adulthood, such as posttraumatic stress disorder (PTSD), triggered by a traumatic event, notably characterized by symptoms related to trauma releif, avoidance and hypervigilance responses. PTSD symptoms reflect stress-induced changes in neurobiological systems and their inadequate adaptation to exposure to intense stressors, with factors contributing to individual vulnerability or resilience to the disorder. The aim of this study was to evaluate the effects of an ELS protocol on maternal care pattern and its consequences on the dynamics of hippocampal activation by proteins related to synaptic plasticity (Egr1, Arc and c-Fos) and in the electrophysiological hippocampal activity/currents (mEPSCs) from P9 to P21, as well as the behavioral consequences and activation of neuronal circuits after a second acute stressor in adulthood, in an experimental PTSD model based on the predator confrontation paradigm. We identified changes in maternal care pattern, notably a higher entropy rate for ELS group, a greater amplitude of mEPSC recordings in P9 ELS, as well as reduced dVenus+ and c-Fos+ cell density in ELS P21. Furthermore, we could observe a qualitative difference in the pattern of activation and distribution of Egr1, Arc and c-Fos positive cells, regardless of the ELS protocol, an indication of developmental changes. We highlight some behavioral differences after exposure to predators between ELS and CTRL groups in the PTSD-like model, such as alterations in escape responses for ELS males and time spent in the burrow for ELS females, as well as an increase in the density of c-Fos+ cells in the PVN of ELS animals that were exposed to trauma. (AU)

• FAPESP's process: 17/10484-6 - Experimental posttraumatic stress disorder: the influence of early life stress and characterization of neural circuits
• Grantee: Nayara Cobra Barreiro Barroca
• Support Opportunities: Scholarships in Brazil - Master