Related Experiment Video
Updated: Sep 13, 2025
Pentylenetetrazole-Induced Kindling Mouse Model
Published on: June 12, 2018
Piezo1 participates in sevoflurane-induced developmental neurotoxicity via neuroinflammation and synaptic damage in
Yang Zhang1, Xinru Liu2, Ying Gao1
1Department of Anesthesiology, First Affiliated Hospital of Bengbu Medical University, Bengbu 233004, China.
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.
Insights
Sevoflurane exposure harms developing brains by increasing Piezo1 activity, leading to neuroinflammation and cognitive deficits. Inhibiting Piezo1 offers a potential therapeutic strategy to protect against this developmental neurotoxicity.
Area of Science:
- Neuroscience
- Toxicology
- Developmental Biology
Background:
- Repeated sevoflurane exposure in neonatal mice causes neurocognitive deficits.
- The role of Piezo1 in sevoflurane-induced developmental neurotoxicity is investigated.
Purpose of the Study:
- To elucidate the mechanisms underlying sevoflurane's neurotoxic effects.
- To determine Piezo1's involvement in sevoflurane-induced developmental neurotoxicity.
Main Methods:
- Neonatal mice were exposed to sevoflurane; Piezo1 function was modulated with GsMTx4 and Yoda1.
- Cognitive function, neuroinflammation, and synaptic integrity were assessed.
- In vitro studies used BV2 microglia to examine Piezo1-mediated calcium signaling.
Main Results:
- Sevoflurane exposure impaired cognitive function, increased neuroinflammation, and damaged synapses, correlating with elevated Piezo1 expression.
- Piezo1 inhibition (GsMTx4) reversed cognitive deficits and neuroinflammation, while activation (Yoda1) worsened outcomes.
- In vitro, sevoflurane increased Piezo1-dependent calcium flux and inflammatory cytokine release in microglia.
Conclusions:
- Piezo1 is a key mediator of sevoflurane-induced developmental neurotoxicity.
- The mechanism involves calcium-dependent microglial complement signaling and synaptic phagocytosis.
- Targeting Piezo1 presents a potential therapeutic avenue for mitigating sevoflurane's adverse effects.
More Related Videos
10:08The Pilocarpine Model of Temporal Lobe Epilepsy and EEG Monitoring Using Radiotelemetry System in Mice
Published on: February 27, 2018
08:23Adaptation of Microelectrode Array Technology for the Study of Anesthesia-induced Neurotoxicity in the Intact Piglet Brain
Published on: May 12, 2018