Wang Yanhong, Chen Yun, Zhang Mengxiao, Yuan Chengdong, Zhang Yu, Liu Xingjian, Zhang Yi, Liang Xiaoli
Department of Anesthesiology, Second Affiliated Hospital of Zunyi Medical University, Zunyi, China.
Department of Anesthesiology, Xishui County People's Hospital, Zunyi, China.
Front Mol Neurosci. 2024 Nov 27;17:1459358. doi: 10.3389/fnmol.2024.1459358. eCollection 2024.
Whether repeated inhalation of sevoflurane during the neonatal period causes long-term learning and memory impairments in humans is unclear. Some recent investigations have indicated that general anesthesia drugs affect histone methylation modification and may further affect learning and memory ability. This study aimed to explore the role and mechanism of histone methylation in long-term cognitive dysfunction caused by repeated inhalation of sevoflurane during the neonatal period.
Neonatal SD rats were assigned into three groups. Sevoflurane group and sevoflurane +AS8351 group were exposed to 2% sevoflurane for 4 h on postnatal day 7 (P7), day 14 (P7) and day 21 (P21), and the control group was inhaled the air oxygen mixture at the same time. From postnatal day 22 to 36, rats in the +AS8351 group were treated with AS8351 while those in the Sevoflurane group and control group were treated with normal saline. Half of the rats were carried out Y-maze, Morris water maze (MWM), western blot and transmission electron microscope at P37, and the remaining rats were fed to P97 for the same experiment.
Neonatal sevoflurane exposure affected histone demethylase expression in hippocampus, changed histone methylation levels, Down-regulated synapse-associated protein expression, impaired synaptic plasticity and long-term cognitive dysfunction and KDM5B inhibitors partially restored the negative reaction caused by sevoflurane exposure.
In conclusion, KDM5B inhibitor can save the long-term learning and memory impairment caused by sevoflurane exposure in neonatal period by inhibiting KDM5B activity.
新生儿期反复吸入七氟醚是否会导致人类长期学习和记忆障碍尚不清楚。最近的一些研究表明，全身麻醉药物会影响组蛋白甲基化修饰，并可能进一步影响学习和记忆能力。本研究旨在探讨组蛋白甲基化在新生儿期反复吸入七氟醚所致长期认知功能障碍中的作用及机制。
将新生SD大鼠分为三组。七氟醚组和七氟醚+AS8351组在出生后第7天（P7）、第14天（P14）和第21天（P21）暴露于2%七氟醚4小时，对照组同时吸入空气-氧气混合气体。从出生后第22天至36天，+AS8351组大鼠用AS8351治疗，而七氟醚组和对照组大鼠用生理盐水治疗。一半的大鼠在P37时进行Y迷宫、莫里斯水迷宫（MWM）、蛋白质免疫印迹法和透射电子显微镜检查，其余大鼠饲养至P97进行相同实验。
新生儿期七氟醚暴露影响海马中组蛋白去甲基化酶表达，改变组蛋白甲基化水平，下调突触相关蛋白表达，损害突触可塑性和长期认知功能障碍，KDM5B抑制剂部分恢复了七氟醚暴露引起的不良反应。
总之，KDM5B抑制剂可通过抑制KDM5B活性挽救新生儿期七氟醚暴露所致的长期学习和记忆损伤。
