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Schizophrenia-associated complement C4 impairs synaptic connectivity and decreases microglia-synapse interactions through CR3 signaling - PubMed

7 hours ago
  • #complement system
  • #microglia
  • #schizophrenia
  • High-expression variants of complement C4 gene increase schizophrenia risk.
  • C4 overexpression (C4-OE) in mouse frontal cortex lowers synapse density and mimics schizophrenia phenotypes.
  • C4-OE effects on synapse density and function are rescued in CR3-deficient mice, indicating CR3 involvement.
  • C4-OE reduces microglial surveilled volume, motility, and contacts with synaptic structures, contrary to excessive elimination models.
  • CR3 deficiency abolishes microglial changes, suggesting CR3 mediates microglia-synapse interaction modulation in schizophrenia.