Microglia mediate memory dysfunction via excitatory synaptic elimination in a fracture surgery mouse model

Autor: Shuming Li, Huan Liu, Pin Lv, Yu Yao, Liangyu Peng, Tianjiao Xia, Chao Yan, Zhengliang Ma, Zhang-Peng Chen, Chunjie Zhao, Xiaoping Gu
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Journal of Neuroinflammation, Vol 21, Iss 1, Pp 1-19 (2024)
Druh dokumentu: article
ISSN: 1742-2094
DOI: 10.1186/s12974-024-03216-2
Popis: Abstract Cognitive impairment is a common issue among human patients undergoing surgery, yet the neural mechanism causing this impairment remains unidentified. Surgical procedures often lead to glial cell activation and neuronal hypoexcitability, both of which are known to contribute to postoperative cognitive dysfunction (POCD). However, the role of neuron-glia crosstalk in the pathology of POCD is still unclear. Through integrated transcriptomics and proteomics analyses, we found that the complement cascades and microglial phagocytotic signaling pathways are activated in a mouse model of POCD. Following surgery, there is a significant increase in the presence of complement C3, but not C1q, in conjunction with presynaptic elements. This triggers a reduction in excitatory synapses, a decline in excitatory synaptic transmission, and subsequent memory deficits in the mouse model. By genetically knockout out C3ar1 or inhibiting p-STAT3 signaling, we successfully prevented neuronal hypoexcitability and alleviated cognitive impairment in the mouse model. Therefore, targeting the C3aR and downstream p-STAT3 signaling pathways could serve as potential therapeutic approaches for mitigating POCD.
Databáze: Directory of Open Access Journals
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