Ricerc@Sapienza

Stress has important effects on brain functions inducing long-lasting effects on both cognition and emotions. On one hand, these effects depend on individual's ability to cope with stress, wherein coping is defined as the behavioral, psychological and physiological effort to master a stressful situation. Therefore, coping strategies are the major determinant of stress resilience or vulnerability. In general, resilient or hardy individuals use active coping strategies when facing stressful life experiences. The appraisal and development of stress-coping strategies is controlled by cortico-limbic areas. On the other hand, stress-coping behavior style depends on genetic, epigenetic and environmental factors. Among epigenetic modulators of gene expression, microRNAs (miRs) have emerged as key regulators of the neurobiological processes controlling the stress response. In particular, miRs belonging to the miR-34 family have been linked to pathogenesis of psychopathologies, including depression, characterized by alterations in coping strategies to stress. Thus, genetic differences in miR-34 expression may contribute to individual stress coping response, making circulating levels of this specific miR a useful biomarker for identifying vulnerable/resilient individuals. Accordingly, we have shown that down-regulation miR-34 expression is associated to resilience to the effects of stress and with a significant reduction of the prefrontal-cortex-amygdala neurochemical response in mouse.Using a translational approach, this project aims to investigate in the animal model and in healthy humans: i) whether individual differences in miR-34 expression are able to predict differences in behavioral response to stress, as determined by their cognitive performance following stress exposure; ii) the role of the prefrontal-cortex-amygdala circuit in mediating the relationship between individuals' coping style, their s¿ miR-34 expression and cognitive performance.