Neurotoxicology · 2025
Sevoflurane exposure in juvenile causes persistent learning and memory impairment via inducing endoplasmic reticulum stress in caenorhabditis elegans and mice.
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Zhao Ayang, Jin Hongjiang, Ma Xiaofei, Fan Guibo, Gao Yueyue, Rong Yuting, Sun Siqi, Zhang Ao, Qi Sihua
Аннотация
BACKGROUND: Exposure to general anesthetics during early postnatal development is linked to enduring cognitive deficits in rodent and non-human primate models. However, the mechanisms by which inhaled anesthetics induce neuronal death and synaptic alterations remain unclear.
METHODS: C. elegans and neonatal male mice were administered sevoflurane. Subsequently, their learning and memory capabilities were assessed, and the potential mechanisms influencing learning and memory in C. elegans and mice were explored.
RESULTS: Early developmental exposure to sevoflurane resulted in learning and memory impairment in C. elegans. The eIF3l and ced-3 genes are critical for sevoflurane-induced developmental neurotoxicity in C. elegans. Endoplasmic reticulum stress is a possible mechanism underlying developmental neurotoxicity induced by sevoflurane in C. elegans. In neonatal mice, sevoflurane induced endoplasmic reticulum stress in hippocampal neurons independently of eIF3l, which was mitigated by TUDCA ( tauroursodeoxycholic acid, an ER stress inhibitor). Additionally, mature mice exposed to sevoflurane during the neonatal period exhibited decreased synaptic function in the hippocampus, which was alleviated by TUDCA. Persistent cognitive dysfunction was observed in adult mice exposed to sevoflurane during the neonatal period, which was alleviated by TUDCA.
CONCLUSION: Our findings demonstrate that early developmental exposure to sevoflurane induces endoplasmic reticulum stress, which may result in a decrease in memory and learning capabilities. TUDCA may alleviate these effects.
METHODS: C. elegans and neonatal male mice were administered sevoflurane. Subsequently, their learning and memory capabilities were assessed, and the potential mechanisms influencing learning and memory in C. elegans and mice were explored.
RESULTS: Early developmental exposure to sevoflurane resulted in learning and memory impairment in C. elegans. The eIF3l and ced-3 genes are critical for sevoflurane-induced developmental neurotoxicity in C. elegans. Endoplasmic reticulum stress is a possible mechanism underlying developmental neurotoxicity induced by sevoflurane in C. elegans. In neonatal mice, sevoflurane induced endoplasmic reticulum stress in hippocampal neurons independently of eIF3l, which was mitigated by TUDCA ( tauroursodeoxycholic acid, an ER stress inhibitor). Additionally, mature mice exposed to sevoflurane during the neonatal period exhibited decreased synaptic function in the hippocampus, which was alleviated by TUDCA. Persistent cognitive dysfunction was observed in adult mice exposed to sevoflurane during the neonatal period, which was alleviated by TUDCA.
CONCLUSION: Our findings demonstrate that early developmental exposure to sevoflurane induces endoplasmic reticulum stress, which may result in a decrease in memory and learning capabilities. TUDCA may alleviate these effects.