Research progress on the role of microglia in the pathogenesis of depression

Depression is a globally prevalent psychiatric disorder associated with reduced life expectancy and a diminished quality of life. Patients with depression commonly experience symptoms such as anhedonia, persistent low mood, and suicidal tendencies, which impose significant societal and familial burdens. Although the etiology of depression remains elusive and its pathogenesis is complex, understanding these mechanisms is critical for guiding effective clinical interventions. Recent research underscores neuroinflammation, driven by microglia—the brain’s key immune cells—as a crucial factor in its pathogenesis. Microglia dynamically regulate brain homeostasis but, under chronic stress, shift to pro-inflammatory states, releasing cytokines like IL-1β and activating pathways like NLRP3 inflammasome and tryptophan-kynurenine metabolism. These processes contribute to neuronal damage and depressive behaviors, with studies showing heightened microglial activity in brain regions like the prefrontal cortex and hippocampus in affected individuals. This review highlights microglia’s dual role in depression, emphasizing inflammation, neuroplasticity, and P2X7 receptor mechanisms as key contributors. Unraveling these interactions is vital for identifying new therapeutic targets, promising improved management of depression through targeting neuroinflammatory pathways.