Microglial Abnormalities in the Pathophysiology of Schizophrenia - Abstract
The etiology of schizophrenia remains unclear while, in many aspects, the neuropathology of schizophrenia has recently been reported to be closely associated with microglia dysfunction. Microglia, which are the major players of innate immunity in the CNS, respond rapidly to even minor pathological changes in the brain and contribute directly to neuroinflammation by producing various pro-inflammatory cytokines and free radicals. Recent human studies have revealed microglial activation in schizophrenia using postmortem brains or in vivo neuroimaging techniques. We and other researchers have recently shown the inhibitory effects of some antipsychotics on the release of inflammatory cytokines and free radicals from activated microglia, both of which have recently been known to cause the synaptic pathology, a decrease in neurogenesis, and white matter abnormalities often found in the brains of patients with schizophrenia. In addition, recent evidence strongly suggests a neurodevelopmental role of microglia in regulating synapse formation/function by their interaction with synapses and phagocytotic activity. It is not known whether microglia dysfunction and microglia-orchestrated neuroinflammation are the primary cause of schizophrenia but they are closely related to the progression and outcomes of schizophrenia. Understanding microglial pathology may shed new light on the therapeutic strategies for schizophrenia.