Ricerc@Sapienza

Chronic or cumulative stress sustained over a long period of time increases the risk of affective illness. Mounting clinical and preclinical evidences support the involvement of non-coding RNA such as microRNAs (miRs) in the long-term adaptive (and maladaptive) response of the brain to psychological stressors. Among miRs, the miR-34 family plays a role in stress-related psychiatric conditions and in the neurobiological mechanisms that underlie the regulation of stress response.
Our recent data demonstrated an important role of miR-34a in mouse Dorsal Raphe Nuclei (DRN) in regulating the stress response. We found that the miR-34a is expressed with high level
and specificity in the DRN and we demonstrated that is implied in the behavioral and neurochemical response to stress.
In this research proposal we hypothesize that miR-34 involvement in stress-coping response may be acting through GABAergic signaling in DRN. After selective DRN miR-34 deletion, we will investigate the role of miR-34 in the behavioral and functional modifications induced in the mouse brain by acute stress exposure. After that, to mimic the chronic adversities exposure that occurs in clinical psychiatric onset, a chronic mild unpredictable stress paradigm will be used to evaluate behavioral and neurochemical phenotype underlying stress vulnerability and resilience.