Ricerc@Sapienza

Resilience and vulnerability to stressful stimuli can influence mood disorders' onset. According to learned helplessness paradigm, different degrees of control that individuals can exert over stressors are a crucial variable in coping response and psychopathological outcome.
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. Our recent works demonstrated an important role of miR-34a in mouse Dorsal Raphe Nuclei (DRN) in regulating stress response. We found that the miR-34a is expressed with high level and specificity in the DRN, exerting a modulatory role on genes related to plasticity as well as stress-related psychiatric illnesses.
In this research proposal we hypothesize that miR-34 specifically interfere with cortical inhibition of DRN, mainly acting on GABA interneurons.
Mir-34 Wild Type and Knockout mice will be exposed to either excapable or inescapable stressors and their depression-like behavior will be evaluated. After that, GABAergic DRN activation in response to this stressful conditions will be analyzed using c-fos expression.