Puech Clementine, Badran Mohammad, Runion Alexandra R, Barrow Max B, Qiao Zhuanhong, Khalyfa Abdelnaby, Gozal David
Child Health Research Institute, Department of Child Health, School of Medicine, University of Missouri, Columbia, MO, USA.
Undergraduate Student Research Program, University of Missouri, Columbia, MO, USA.
Neurobiol Sleep Circadian Rhythms. 2022 Oct 10;13:100084. doi: 10.1016/j.nbscr.2022.100084. eCollection 2022 Nov.
Obstructive sleep apnea (OSA) is a chronic and highly prevalent condition characterized by chronic intermittent hypoxia (IH) and sleep fragmentation (SF), and can lead to a vast array of end-organ morbidities, particularly affecting cardiovascular, metabolic and neurobehavioral functioning. OSA can induce cognitive and behavioral and mood deficits. Male C57Bl/6J 8-week-old mice were housed in custom-designed cages with a silent motorized mechanical sweeper traversing the cage floor at 2-min intervals (SF) during daylight for four weeks. Sleep control (SC) consisted of keeping sweeper immobile. IH consisted of cycling FiO 21% 90 seconds-6.3% 90s or room air (RA; FiO 21%) for sixteen weeks and combined SF-IH was conducted for nine weeks. Open field novel object recognition (NOR) testing, elevated-plus maze test (EPMT), and forced swimming test (FST) were performed. SF induced cognitive NOR performance impairments in mice along with reduced anxiety behaviors while IH induced deficits in NOR performance, but increased anxiety behaviors. SF-IH induced impaired performance in NOR test of similar magnitude to IH or SF alone. Combined SF-IH exposures did not affect anxiety behaviors. Thus, both SF an IH altered cognitive function while imposing opposite effects on anxiety behaviors. SF-IH did not magnify the detrimental effects of isolated SF or IH and canceled out the effects on anxiety. Based on these findings, the underlying pathophysiologic processes underlying IH and SF adverse effects on cognitive function appear to differ, while those affecting anxiety counteract each other.
阻塞性睡眠呼吸暂停（OSA）是一种慢性且高度普遍的病症，其特征为慢性间歇性缺氧（IH）和睡眠片段化（SF），可导致一系列终末器官疾病，尤其影响心血管、代谢和神经行为功能。OSA可引发认知、行为和情绪缺陷。8周龄雄性C57Bl/6J小鼠被安置在定制设计的笼子里，在白天期间，一个静音电动机械清扫器每隔2分钟横穿一次笼底（模拟睡眠片段化），持续四周。睡眠对照组（SC）则是让清扫器保持不动。间歇性缺氧组（IH）是让吸入氧浓度在21%（90秒）-6.3%（90秒）之间循环或吸入室内空气（RA；吸入氧浓度21%），持续16周，而联合睡眠片段化与间歇性缺氧组（SF-IH）持续9周。进行旷场新物体识别（NOR）测试、高架十字迷宫测试（EPMT）和强迫游泳测试（FST）。睡眠片段化导致小鼠认知NOR测试表现受损，同时焦虑行为减少，而间歇性缺氧导致NOR测试表现缺陷，但焦虑行为增加。联合睡眠片段化与间歇性缺氧组（SF-IH）在NOR测试中的表现受损程度与单独的间歇性缺氧组或睡眠片段化组相似。联合暴露于睡眠片段化与间歇性缺氧组（SF-IH）并未影响焦虑行为。因此，睡眠片段化和间歇性缺氧都改变了认知功能，同时对焦虑行为产生相反的影响。联合睡眠片段化与间歇性缺氧组（SF-IH）并未放大单独的睡眠片段化或间歇性缺氧的有害影响，且抵消了对焦虑的影响。基于这些发现，间歇性缺氧和睡眠片段化对认知功能产生不良影响的潜在病理生理过程似乎不同，而对焦虑的影响则相互抵消。
