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  3. Piezo1 participates in sevoflurane-induced developmental neurotoxicity via neuroinflammation and synaptic damage in the hippocampus

Piezo1 participates in sevoflurane-induced developmental neurotoxicity via neuroinflammation and synaptic damage in the hippocampus

  • Int Immunopharmacol. 2025 Jul 26:163:115284. doi: 10.1016/j.intimp.2025.115284.
Yang Zhang 1,  Xinru Liu 2,  Ying Gao 1,  Chengwen Fu 3,  Yanan Xue 1,  Dongsheng Wang 1,  Jin Hong 4,  Li Ren 5,  Liwen Zha 6,  Yunzhi Ling 7,  Congli Zhang 8,  Xiaohong Li 9
Affiliations

Affiliations

  • 1 Department of Anesthesiology, First Affiliated Hospital of Bengbu Medical University, Bengbu 233004, China.
  • 2 Department of Anesthesiology, First Affiliated Hospital of Bengbu Medical University, Bengbu 233004, China; Brain and Neurological Research Laboratory, Bengbu Medical University, Bengbu 233000, China.
  • 3 Department of Anesthesiology, First Affiliated Hospital of Bengbu Medical University, Bengbu 233004, China; Key Laboratory of Cardio-Cerebrovascular Foundation and Clinical Sciences, Bengbu Medical University, Bengbu 233000, China.
  • 4 Department of Anesthesia, Bengbu Medical University, Bengbu 233000, China.
  • 5 Department of Clinical Laboratory Medicine, Bengbu Medical University, Bengbu 233000, China.
  • 6 Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hongkong 999077, China.
  • 7 Department of Anesthesiology, First Affiliated Hospital of Bengbu Medical University, Bengbu 233004, China. Electronic address: ling_yunzhi1977@163.com.
  • 8 Department of Anesthesiology, First Affiliated Hospital of Bengbu Medical University, Bengbu 233004, China; Department of Clinical Laboratory Medicine, Bengbu Medical University, Bengbu 233000, China. Electronic address: byfy1010@163.com.
  • 9 Department of Anesthesiology, First Affiliated Hospital of Bengbu Medical University, Bengbu 233004, China; Brain and Neurological Research Laboratory, Bengbu Medical University, Bengbu 233000, China. Electronic address: lixiaohong9078@163.com.
PMID: 40716188 DOI: 10.1016/j.intimp.2025.115284
Abstract

Background: Multiple exposures to sevoflurane in developmental neonatal mice lead to neurocognitive deficits. The present study investigates the role and mechanisms of Piezo1 in sevoflurane-induced developmental neurotoxicity.

Methods: Neonatal mice received sevoflurane on postnatal days (P) 6, 7, and 8. Piezo1 function was assessed using inhibitor GsMTx4 and agonist Yoda1. Cognitive function was evaluated via behavioral tests. Neuroinflammation was assessed by ELISA, Western blot, and immunofluorescence. Synaptic integrity was analyzed by Golgi staining.

Results: Sevoflurane induced cognitive deficits, neuroinflammation, and synaptic damage, and increased Piezo1 expression. Yoda1 exacerbated cognitive deficits. GsMTx4 rescued cognitive function and synaptic plasticity, reduced microglial phagocytosis, and suppressed complement activation. In vitro, sevoflurane increased Piezo1 expression and intracellular calcium flux in BV2 microglia; GsMTx4 blocked these effects. Yoda1 amplified calcium flux, pro-inflammatory cytokines (TNF-α/IL-6), and C1q expression, which were abolished by calcium chelator BAPTA-AM.

Conclusion: Piezo1 mediates sevoflurane-induced developmental neurotoxicity via calcium-dependent microglial complement signaling and synaptic phagocytosis. Piezo1 inhibition is considered a potential therapeutic strategy.

Keywords

Cognitive deficits; Developmental neurotoxicity; Neuroinflammation; Sevoflurane; Synaptic plasticity.

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