Ricerc@Sapienza

Major depressive disorder (MDD) is one of the most relevant public health challenges at clinical, social and economic levels. One of the main causes of this burden is the limited comprehension of the molecular mechanisms underlying the pathology. Synaptic dysfunction, which has been suggested to be central to MDD, is determined by a complex interplay between different cell types, among which microglia exert a key role. In recent years, these cells were shown to be crucial for regulating synapses and remodeling of neuronal circuits. In the present project, we aim to study microglial implication in synaptic dysfunction in MDD and following exposure to chronic stress, the major risk factor for MDD. A further aim is to investigate the microglial role in the remission from MDD, which has been only limitedly explored. To these goals, we will exploit a multidisciplinary approach and our analyses will range from molecular, to electrophysiology, imaging and behavioral phenotyping. By focusing on microglia-synapse interactions, our project will provide novel insights into the molecular and cellular mechanisms underlying synaptic dysfunction in MDD and represent a point of major importance for the future development of novel therapeutic strategies that specifically target microglia, thus advancing the field of MDD treatment that has not substantially progressed over the last decades.