Effects of early life stress and Egr1 gene expression in the hippocampal synaptic plasticity

• Grant number: 18/21240-3
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• Effective date (Start): May 01, 2019
• Effective date (End): October 31, 2019
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal Investigator: Norberto Garcia Cairasco
• Grantee: Nayara Cobra Barreiro Barroca
• Supervisor: Harm J. Krugers
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Research place: University of Amsterdam (UvA), Netherlands
• Associated to the scholarship: 17/10484-6 - Experimental posttraumatic stress disorder: the influence of early life stress and characterization of neural circuits, BP.MS

Abstract

Stressful situations during early life (early life stress, ELS), such as physical, sexual and emotional abuse or neglect, are associated with a higher risk of developing psychopathologies in adult life, like posttraumatic stress disorder (PTSD), which is triggered by a traumatic event, and is characterized by inappropriate processing of emotional information resulting in anxiety, revival, avoidance behavior and hypervigilant responses. Enhanced risk for developing stress-related psychopathology may be related to ELS-induced alterations in neuronal morphology and function in areas that are critical for emotional memory processing such as the hippocampus. In particular, altered hippocampal function has been related to reduced contextualization, and consequently, generalized fear responses. A critical question that remains elusive is exactly how changes early in life can have such persistent effects on hippocampal function. In this project we will test the role of early growth response 1 (Egr1), which regulates synaptic function, synaptic plasticity and epigenetic modification of receptors for stress-hormones, and preliminary data from the University of Amsterdam (UvA) group indicates the Egr1 expression is affected by ELS. In the main project, we aim to assess if stress experienced during early periods of postnatal development is related to a greater behavioral response in an experimental PTSD model and to analyze neurobiological substrates that may be related to the etiology and course of the disorder. In this BEPE-Project, we intend to assess the immediate ELS impacts on synaptic plasticity and its relation with Egr1 gene expression. To do so, we will use an animal model of early life stress (ELS), in which there is an abnormal and fragmented maternal care, and evaluate synaptic plasticity by electrophysiological assessment. After that, we will modulate the Egr1 expression in ELS animals using molecular tools, aiming to revert the possible ELS impacts on synaptic function and plasticity. These studies will provide a first step to uncover the molecular pathways that lead to altered neuronal function and related behaviour after ELS. (AU)