C3 and major depressive disorder: The enrichment of pathways like NOD-like receptor signaling and Fc gamma R-mediated phagocytosis in C3−/− microglia aligns with recent studies showing the C3-C3aR pathway as a key mediator of microglial activation, neuroinflammation, and interactions with astrocytes, contributing to neurodegeneration and depression (24, 64, 65).