Pathophysiology of post-traumatic stress symptoms: searching for intermediate phenotypes of re-experiencing in an animal model.

Proponente Simona Cabib - Professore Ordinario
Sottosettore ERC del proponente del progetto
Componenti gruppo di ricerca

Post-Traumatic Stress Disorder (PTSD) is a severe and debilitating disturbance with a lifetime prevalence estimate of 0.3% to 6.1%. Although it is amongst the very few mental diseases with a recognized pathogen -the experience of an extreme stressful event- the psychobiological processes leading to PTSD are still poorly understood. The search for intermediate phenotypes (IPs) -specific brain-based pathophysiological mechanisms leading to altered brain function and specific symptoms- has been recently proposed as a promising strategy. The proposed research is aimed at identifying IPs underlying persistent relapses of trauma-related memories in PTDS using a translational approach.
The first year of this 3-years project will be dedicated to the development of an animal model of a recognized PTDS pathogenic trajectory in mice. The pathogenic trajectory to be modeled is based on clinical and preclinical evidences supporting an interaction between sex, early childhood adversities, and proximal trauma in the development of severe re-experiencing symptoms and higher levels of physiological reactivity to trauma recalling. The model is based on preliminary results indicating that the experience of an unstable maternal environment (repeated cross-fostering [RCF]) moderates stress-induced neuroplasticity within the medial pre-Frontal Cortex (mpFC) of adult C57BL/6 mice sex-dependently. Indeed, learning- induced plasticity in mpFC is involved in acquisition and extinction of fear-related memories in either human or non-human animals.
In the first year we plan to perform the following experiments: 1. Test the effects of a proximal acute stress on acquisition and extinction of conditioned fear in RCF adult male and female mice; 2. Test the hypothesis of a parallel influence of estrogens on behavioral and neuroplastic effects of stress in RCF adult female mice.

LS5_2, LS5_5, SH4_6

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