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Published on: February 2, 2017
Environmental enrichment mitigates sevoflurane-induced neurodevelopmental injury via cGAS-STING-dependent microglial
Feixiang Li1, Bingqing Gong2, Haiyan Wu3
1Anesthesia & Operation Center, Beijing Chao-Yang Hospital, Capital Medical University, Beijing Key Laboratory of Precision Translational Medicine in Anesthes, Beijing, 100020, China. lfxone@126.com.
Background:
Neonatal exposure to sevoflurane has been implicated in long-term neurodevelopmental abnormalities, yet the underlying mechanisms remain unresolved. This study sought to determine whether cGAS-STING-mediated microglial activation and aberrant synaptic pruning underlie sevoflurane-induced cognitive deficits and to assess how environmental conditions modulate these processes.
Methods:
Neonatal mice underwent sevoflurane exposure followed by rearing in enriched (EE) or impoverished (IE) environments. Cognitive function, synaptic structure, microglial activity, mitochondrial status, and cGAS-STING signaling were evaluated using behavioral tests, immunostaining, biochemical assays, and pharmacological inhibition.
Results:
Sevoflurane exposure induced cognitive impairment, microglial overactivation, mitochondrial dysfunction, and excessive synaptic pruning resulting from microglial overactivation. EE mitigated these abnormalities by preserving mitochondrial integrity and reducing mtDNA-driven cGAS-STING activation, thereby preventing the microglia-mediated imbalance in synaptic pruning and improving cognitive outcomes. In contrast, IE exacerbated mitochondrial injury, aggravated synaptic loss, and further worsened cognitive impairment.
Conclusion:
Sevoflurane disrupts neurodevelopment through a mitochondria-cGAS-microglia-synapse pathway. Environmental enrichment offers significant neuroprotection, highlighting both cGAS-STING signaling and early-life environmental modulation as promising targets for preventing anesthesia-related neurodevelopmental injury.
