Sanfilippo-Cohn Benjamin, Lai Saien, Zhan Guanxia, Fenik Polina, Pratico Domenico, Mazza Emilio, Veasey Sigrid C
Center for Sleep and Respiratory Neurobiology and Department of Medicine, University of Pennsylvania, Philadelphia 19104, USA.
Sleep. 2006 Feb;29(2):152-9. doi: 10.1093/sleep/29.2.152.
Adult male mice exposed to long-term intermittent hypoxia (LTIH), modeling sleep apnea oxygenation patterns, develop nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent residual hypersomnolence and oxidative injury in select brain regions, including wake-active regions. Premenopausal females are less susceptible to selective oxidative brain injuries. We sought to determine whether female mice exposed to LTIH would confer resistance to LTIH-induced wake impairments and oxidative injuries.
Young adult male and female C57BI/6J mice were studied in a university laboratory.
Mice were randomly assigned to either LTIH or sham LTIH for 8 weeks. Total (24-h) wake time and mean sleep latency were measured under 2 conditions: rested and following 6 hours of enforced wakefulness. NADPH oxidase activation, carbonylation, and lipid peroxidation assays were also performed to assess sex differences in oxidative responses to LTIH.
In contrast with the significant LTIH-induced wake impairments observed in male mice, females following LTIH showed normal wake times and sleep latencies. Female mice revealed less baseline carbonylation and less carbonylation following LTIH but showed robust NADPH oxidase activation and lipid peroxidation. In contrast with the female relative resistance to LTIH sleepiness, female mice showed more-pronounced sleepiness and delta response after enforced wakefulness.
Despite a robust oxidative response to LTIH, age-matched female mice may be protected, at least temporarily, from LTIH wake impairments by lower basal carbonylation. In contrast, females show greater wake impairments after sleep deprivation. We hypothesize sex differences in polysomnographic predictors of sleepiness and residual sleepiness in humans with sleep apnea.
成年雄性小鼠暴露于长期间歇性低氧（LTIH）环境中，模拟睡眠呼吸暂停时的氧合模式，会在包括觉醒活跃区域在内的特定脑区出现烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶依赖性的残余嗜睡和氧化损伤。绝经前女性对选择性脑氧化损伤的易感性较低。我们试图确定暴露于LTIH的雌性小鼠是否能抵抗LTIH诱导的觉醒障碍和氧化损伤。
在大学实验室中对年轻成年雄性和雌性C57BI/6J小鼠进行研究。
将小鼠随机分为LTIH组或假LTIH组，为期8周。在两种条件下测量总（24小时）觉醒时间和平均睡眠潜伏期：休息状态下以及强制觉醒6小时后。还进行了NADPH氧化酶激活、羰基化和脂质过氧化测定，以评估对LTIH氧化反应的性别差异。
与雄性小鼠中观察到的LTIH诱导的显著觉醒障碍相反，LTIH后的雌性小鼠觉醒时间和睡眠潜伏期正常。雌性小鼠基线羰基化水平较低，LTIH后羰基化增加较少，但显示出强烈的NADPH氧化酶激活和脂质过氧化。与雌性对LTIH嗜睡的相对抗性相反，雌性小鼠在强制觉醒后表现出更明显的嗜睡和δ波反应。
尽管对LTIH有强烈的氧化反应，但年龄匹配的雌性小鼠可能因较低的基础羰基化水平而至少暂时免受LTIH觉醒障碍的影响。相比之下，雌性在睡眠剥夺后表现出更大的觉醒障碍。我们推测睡眠呼吸暂停患者在多导睡眠图嗜睡和残余嗜睡预测指标上存在性别差异。
