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Zhao, Ming‐ming; Gu, Han‐wen; Pan, Wei‐tong; Liu, Pan‐miao; Zhu, Ting‐ting; Shang, Hui‐jie; Jia, Min; Yang, Jian‐jun
CNS neuroscience & therapeutics, January 2024, Volume: 30, Issue: 1Journal Article
Aims Sevoflurane is widely used for general anesthesia in children. Previous studies reported that multiple neonatal exposures to sevoflurane can induce long‐term cognitive impairment in adolescent rats, but the underlying mechanisms were not defined. Methods Postnatal day 6 (P6) to P8 rat pups were exposed to 30% oxygen with or without 3% sevoflurane balanced with air. The Y maze test (YMT) and Morris water maze (MWM) tests were performed in some cohorts from age P35 to assess cognitive functions, and their brain samples were harvested at age P14, 21, 28, 35, and 42 for measurements of various molecular entities and in vivo electrophysiology experiments at age P35. Results Sevoflurane exposure resulted in cognitive impairment that was associated with decreased synCAM1 expression in parvalbumin (PV) interneurons, a reduction of PV phenotype, disturbed gamma oscillations, and dendritic spine loss in the hippocampal CA3 region. Enriched environment (EE) increased synCAM1 expression in the PV interneurons and attenuated sevoflurane‐induced cognitive impairment. The synCAM1 overexpression by the adeno‐associated virus vector in the hippocampal CA3 region restored sevoflurane‐induced cognitive impairment, PV phenotype loss, gamma oscillations decrease, and dendritic spine loss. Conclusion Our data suggested that neonatal sevoflurane exposure results in cognitive impairment through decreased synCAM1 expression in PV interneurons in the hippocampus. Neonatal exposure to repeated sevoflurane anesthesia resulted in cognitive impairment associated with decreased synCAM1 expression in the hippocampal PV interneurons, reduced PV interneurons phenotype, and disturbed gamma oscillations. Moreover, overexpression of synCAM1 in the hippocampal PV interneurons improved cognitive function by restoring PV expression and gamma oscillations after repeated sevoflurane exposure.
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