Microglia in Bipolar Disorder: Roles in Cell Communication and State-Dependent Alterations
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Microglia, the central nervous system’s (CNS) resident immune cells, are indispensable for neural homeostasis, synaptic plasticity, and neuroimmune crosstalk. In bipolar disorder (BD) which is a serious mental disorder, emerging evidence reveals that microglial dysfunction diverges from classical neuroinflammatory activation, instead manifesting as subtle phenotypic shifts that perturb neuron–glia communication. Recent studies identify altered receptor expressions (e.g., CX3CR1, CD206 which disrupt synaptic pruning, neurotrophic signaling, and cytokine balance. Critically, microglial activity fluctuates with mood states, manic phases correlate with hyper-ramified morphology, while depressive episodes associate with synaptic dysregulation. Advances in neuroimaging and induced microglia-like (iMG) models now enable precise dissection of these state-dependent changes, offering pathways for therapies targeting microglial modulation.
