GSE123027
The role microglia in electroconvulsive threapy (ECT) in depressed-like mice
Recent studies implicate microglia alterations in the pathogenesis and pathophysiology of depression. For example, chronic unpredictable stress (CUS) in mice can cause degeneration of microglia and depressive-like symptoms, which can be reversed by microglia stimulating drugs. To further test the causal role of microglia in CUS-induced depression and its reversal by an anti-depressive procedure, we examined the effects of microglia depletion with the CSF-1 antagonist PLX5622 or pharmacological blockade of microglial activation with minocycline on normal mood-related behavior, CUS-induced depressive-like symptoms, and the amelioration of these symptoms by electroconvulsive treatment (ECT). We report that microglia-depleted mice showed no depression, anxiety or spatial memory disturbances. Microglia depletion had no effect on the development of CUS-induced depressive-like symptoms and suppressed neurogenesis, but it completely abrogated the beneficial effects of ECT on depression and neurogenesis, as well as on the all ECT-induced transcriptomic changes. ECT induced several morphological changes in microglia, suggestive of increased activation status, and blockade of this activation by minocycline attenuated the anti-depressive and pro-neurogenesis effect of ECT and reduced the number of contacts between microglia and neurogenic cells. The immune checkpoint gene Lag3, whose expression by microglia was increased following CUS, was the only microglial transcript significantly reduced by ECT. Furthermore, treatment of depressed-like mice with a LAG3 monoclonal antibody was further tested. Overall design: 2*2  Chornic unpredictable stress exposed mice treated with ECT/SHAM* Control Diet/PLX Diet. There is an extra control non-stressed group.