2. Academic Validation
  3. A complement-microglial axis driving inhibitory synapse related protein loss might contribute to systemic inflammation-induced cognitive impairment

A complement-microglial axis driving inhibitory synapse related protein loss might contribute to systemic inflammation-induced cognitive impairment

  • Int Immunopharmacol. 2020 Oct;87:106814. doi: 10.1016/j.intimp.2020.106814.
Shu-Ming Li 1,  Bin Li 1,  Ling Zhang 1,  Guang-Fen Zhang 1,  Jie Sun 1,  Mu-Huo Ji 2,  Jian-Jun Yang 3
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China.
  • 2 Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. Electronic address: [email protected].
  • 3 Department of Anesthesiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China; Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. Electronic address: [email protected].
PMID: 32707491 DOI: 10.1016/j.intimp.2020.106814
Abstract

Systemic inflammation induces cognitive impairments via unclear mechanisms. Increasing evidence has suggested complement C3/C3a receptor signaling, a key component of innate immune pathogen defense, plays an important role in cognition and neurodegeneration, whereas its dysfunction is implicated in many neurological disorders. However, it remains unclear whether complement C3/C3a receptor signaling was involved in systemic inflammation-induced cognitive impairments. In the present study, we showed that hippocampal complement C3 levels in astrocytes and C3a receptor expressions in microglia were specifically up-regulated after lipopolysaccharide (LPS) injection. Interestingly, LPS selectively induced inhibitory but not excitatory synapse related protein loss. Notably, C3a receptor antagonist SB290157 trifluoroacetate attenuated LPS-induced hippocampal neuroinflammation and inhibitory synapse related protein loss, contributing to improved cognitive function. In conclusion, our study suggests that complement C3/C3a receptor signaling plays a key role in LPS-induced cognitive impairments, which may serve a therapeutic target for systemic inflammation related cognitive disorders.

Keywords

Cognition; Complement C3; Microglia; Synapse.

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