背景:由于医疗需要,孕妇可能需要在全身麻醉下进行非产科手术,孕妇在妊娠后期经常会出现睡眠障碍。临床前研究表明,母亲异氟烷暴露(MISO)或母亲睡眠剥夺(MSD)有助于后代的认知障碍。对小鼠的研究表明,SD可以加重异氟烷引起的认知缺陷。然而,目前尚不清楚MSD是否会加重MISO诱导的后代认知缺陷.本研究的目的是探讨MSD和MISO对子代认知功能的联合作用以及神经炎症和突触功能在MSD+MISO过程中的作用。
方法:在妊娠日(GD)14,通过吸入将妊娠小鼠暴露于1.4%异氟烷4小时。然后在GD15-21期间对大坝进行SD处理6小时(12:00-18:00小时)。在3个月大的时候,对后代小鼠进行Morris水迷宫测试以评估认知功能。然后使用分子生物学方法评估炎症和抗炎标志物以及突触功能相关蛋白的水平。
结果:这项研究的结果表明,MISO导致认知功能障碍,MSD加剧了这种影响。此外,MSD加剧了母体异氟烷吸入,导致白细胞介素(IL)-1β的表达水平增强,IL-6和肿瘤坏死因子-α,以及IL-10,突触素,突触后密度-95、生长相关蛋白-43和脑源性神经营养因子。
结论:我们的发现表明,MSD加重了雄性后代小鼠MISO诱导的认知缺陷,这些结果与神经炎症和突触功能的改变有关。
BACKGROUND: Pregnant women may need to undergo non-obstetric surgery under general anesthesia owing to medical needs, and pregnant women frequently experience sleep disturbances during late gestation. Preclinical studies demonstrated that maternal isoflurane exposure (MISO) or maternal sleep deprivation (MSD) contributed to cognitive impairments in offspring. Research studies in mice have revealed that SD can aggravate isoflurane-induced cognitive deficits. However, it remains unclear whether MSD aggravates MISO-induced cognitive deficits in offspring. The purpose of this research was to explore the combined effects of MSD and MISO on offspring cognitive function and the role of neuroinflammation and synaptic function in the process of MSD + MISO.
METHODS: Pregnant mice were exposed to 1.4% isoflurane by inhalation for 4 h on gestational day (GD) 14. Dams were then subjected to SD for 6 h (12:00-18:00 h) during GD15-21. At 3 months of age, the offspring mice were subjected to the Morris water maze test to assess cognitive function. Then the levels of inflammatory and anti-inflammatory markers and synaptic function-related proteins were assessed using molecular biology methods.
RESULTS: The results of this study demonstrated that MISO led to cognitive dysfunction, an effect that was aggravated by MSD. In addition, MSD exacerbated the maternal isoflurane inhalation, leading to an enhancement in the expression levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha and a reduction in the hippocampal levels of IL-10, synaptophysin, post-synaptic density-95, growth-associated protein-43, and brain-derived neurotrophic factor.
CONCLUSIONS: Our findings revealed that MSD aggravated the cognitive deficits induced by MISO in male offspring mice, and these results were associated with neuroinflammation and alternations in synaptic function.