Abstract # 3109 Alterations in microglia and their interaction with adult newborn (neurogenic) cells in the hippocampus underlie the anti-depressive effects of electroconvulsive therapy (ECT)

Abstract

Studies in our laboratory demonstrated that the development of depressive symptoms following exposure to chronic unpredictable stress (CUS) in mice is associated with microglia decline and dystrophy. Consistently, microglia stimulating drugs, such as LPS or M-CSF, reversed the depressive-like condition in CUS-exposed rodents. Electroconvulsive therapy (ECT) is one of the most effective treatments for depression. Although it has been used for decades, the mechanisms underlying ECT’s action are still elusive. We report here that the anti-depressive effects of ECT in CUS-exposed mice were associated with alterations in microglia density and morphology indicative of activation. This activation is crucial for the anti-depressive effects of ECT, because in mice treated with minocycline concomitantly with ECT these effects were diminished. Facilitation of hippocampal adult neurogenesis is considered an important mechanism of action of anti-depressive procedures. To test the role of microglia in these effects we first demonstrated that following microglia depletion (induced by PLX5622), the elimination, formation, maintenance and circuit integration of synapses on newborn (but not mature) cells were impaired. We next showed that minocycline blocked the positive effects of ECT on neurogenesis in “depressed-like” mice, by reducing the contacts between microglia and neurogeneic (doublecortin-positive) cells. These findings suggest that the effects of ECT on hippocampal microglia and their contacts with newborn cells are essential for restoration of hippocampal neurogenesis, resulting in reversal of stress-induced depression.