PROJECT: JTC2017: MicroSynDep

Major depressive disorder (MDD) is one of the most relevant public health challenges. 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 and integrated approach that combines studies conducted in animal models, in post-mortem brain samples from depressed individuals, and a clinical trial. Our analyses will range from cellular and subcellular neuroimaging, high-throughput molecular biology, state-of-the-art microglia-based Omics, to classical electrophysiology, and behavioral phenotyping. By focusing on microglia-synapse interactions, our project will provide novel insights into the molecular cellular and 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.