Department of Anaesthesiology, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.
School of Life Sciences, China Medical University, Shenyang, People's Republic of China.
Br J Anaesth. 2024 Oct;133(4):810-822. doi: 10.1016/j.bja.2024.05.047. Epub 2024 Aug 13.
Repeated exposure to sevoflurane during early developmental stages is a risk factor for social behavioural disorders, but the underlying neuropathological mechanisms remain unclear. As the hippocampal cornu ammonis area 2 subregion (CA2) is a critical centre for social cognitive functions, we hypothesised that sevoflurane exposure can lead to social behavioural disorders by disrupting neuronal activity in the CA2.
Neonatal mice were anaesthetised with sevoflurane 3 vol% for 2 h on postnatal day (PND) 6, 8, and 10. Bulk RNA sequencing of CA2 tissue was conducted on PND 12. Social cognitive function was assessed by behavioural experiments, and in vivo CA2 neuronal activity was recorded by multi-channel electrodes on PND 60-65.
Repeated postnatal exposure to sevoflurane impaired social novelty recognition in adulthood. It also caused a decrease in the synchronisation of neuronal spiking, gamma oscillation power, and spike phase-locking between GABAergic spiking and gamma oscillations in the CA2 during social interaction. After sevoflurane exposure, we observed a reduction in the density and dendritic complexity of CA2 GABAergic neurones, and decreased expression of transcription factors critical for GABAergic neuronal development after.
Repeated postnatal exposure to sevoflurane disturbed the development of CA2 GABAergic neurones through downregulation of essential transcription factors. This resulted in impaired electrophysiological function in adult GABAergic neurones, leading to social recognition deficits. These findings reveal a potential electrophysiological mechanism underlying the long-term social recognition deficits induced by sevoflurane and highlight the crucial role of CA2 GABAergic neurones in social interactions.
在早期发育阶段反复接触七氟醚是社交行为障碍的一个风险因素，但潜在的神经病理学机制尚不清楚。由于海马角 2 亚区（CA2）是社交认知功能的关键中心，我们假设七氟醚暴露可通过破坏 CA2 中的神经元活动导致社交行为障碍。
在出生后第 6、8 和 10 天，用 3%七氟醚麻醉新生小鼠 2 小时。在出生后第 12 天对 CA2 组织进行大规模 RNA 测序。通过行为实验评估社交认知功能，在出生后第 60-65 天通过多通道电极记录 CA2 神经元活动。
反复的产后暴露于七氟醚可损害成年后的社交新异性识别能力。它还导致在社交互动期间 CA2 中 GABA 能神经元的尖峰同步性、γ 振荡功率以及尖峰相位锁定到 γ 振荡的减少。在七氟醚暴露后，我们观察到 CA2 GABA 能神经元的密度和树突复杂性降低，并且在以后关键的转录因子表达减少。
反复的产后暴露于七氟醚通过下调关键的转录因子扰乱 CA2 GABA 能神经元的发育。这导致成年 GABA 能神经元的电生理功能受损，导致社交识别缺陷。这些发现揭示了七氟醚引起的长期社交识别缺陷的潜在电生理机制，并强调了 CA2 GABA 能神经元在社交互动中的关键作用。
