Ricerc@Sapienza

Exposure to traumatic stressors causes long lasting changes in emotionality and behavior increasing susceptibility to disease and mental disorders. Many studies had reported that stress is able to impair specific synaptic functions in neural circuit that plays a key role in development and expression of stress-related disorders. Epigenetic factors have emerged as one of the most promising areas for earlier prevention and novel therapy for stress-related disorders and it has been demonstrated that microRNAs (miRs) play a central role in epigenetic regulation of several psychiatric disorders.
Consistently, different reports suggest a crucial role for miRs in modulating neurobiological processes, including dendritic morphological changes and neurotransmitters homeostasis. MicroRNAs (miRs)-34 have recently been implicated in emotional responses to stress and pathogenesis of psychopatologies. Interestingly, miRNAs can exert their action also locally at the level of synapses and thus regulate the experience-dependent remodeling specific neural circuits, with obvious implications for neuropsychiatric disorders. In order to improve our understanding of the regulatory function of miRNAs in the brain and exploit the miRNAs for the design of new drugs, the cell-type specific expression need to be identified.
On the basis of our preliminary data the present project will evaluate, in mouse model of stress, the role of miR-34a in the selective regulation of GABAergic transmission in the dorsal raphe nuclei (DRN). Moreover the implication of this regulation on the manifestation of depressive-like phenotypes following exposure to chronic stress will be evaluated.