Paraquat induces microglial cause early neuronal synaptic deficits through activation of the classical complement cascade response

Abstract

Synapse loss is considered to be an early event in the dysfunction of the central nervous system (CNS), precedes neuronal decline, which is the main pathological change in mild cognitive impairment (MCI). Accumulating evidence has shown that neuronal synapse loss is associated with hyperactivity of microglial phagocytosis. In the CNS, microglia act as macrophages to clear cellular debris and weakened synapses, but the mechanism by which microglia activation leads to phagocytosis disorder remains unclear. Therefore, we treated mice with paraquat (PQ) in intraperitoneal injection to explore the mechanism by which microglia exert immunotoxicity in the CNS and cause neuronal synapse loss. Immunofluorescence results exposed synapses decreased with PQ exposure time, but the staining HE and Nissl showed that neuronal cell bodies were hardly affected. Fluorescence co-localization found that C1q (classical complement cascade initiation factor) was gradually deposited in the postsynaptic membrane of neurons to trigger the cascade reaction, thereby causing the excessive deposition of C3, a key factor of the classical complement cascade, and further induces hyperactivation of microglia, leads to phagocytosis disorder. IHC results demonstrated that the parallel relationship. Therefore, all our preliminary results throw light on the mechanism by which PQ abnormally triggers the immune system to produce immunotoxicity leading to microglial phagocytic dysfunction.