Obstructive sleep apnea (OSA), a chronic sleep disorder characterized by repetitive reduction or cessation of airflow during sleep, is widely prevalent and is associated with adverse neurocognitive sequelae including increased risk of Alzheimer's disease (AD). In humans, OSA is more common in elderly males. OSA is characterized by sleep fragmentation and chronic intermittent hypoxia (CIH), and recent epidemiological studies point to CIH as the best predictor of neurocognitive sequelae associated with OSA. The sex- and age- specific effects of OSA-associated CIH on specific cell populations such as γ-aminobutyric acid (GABA)-ergic neurons in the hippocampus and the medial prefrontal cortex (mPFC), regions important for cognitive function, remain largely unknown. The present study examined the effect of 35 days of either moderate (10% oxygen) or severe (5% oxygen) CIH on GABAergic neurons in the mPFC and hippocampus of young and aged male and female mice as well as post-accelerated ovarian failure (AOF) female mice. In the mPFC and hippocampus, the number of GABA-labeled neurons increased in aged and young severe CIH males compared to controls but not in young moderate CIH males. This change was not representative of the individual GABAergic cell subpopulations, as the number of parvalbumin-labeled neurons decreased while the number of somatostatin-labeled neurons increased in the hippocampus of severe CIH young males only. In all female groups, the number of GABA-labeled cells was not different between CIH and controls. However, in the mPFC, CIH increased the number of parvalbumin-labeled neurons in young females and the number of somatostatin-labeled cells in AOF females but decreased the number of somatostatin-labeled cells in aged females. In the hippocampus, CIH decreased the number of somatostatin-labeled neurons in young females. CIH decreased the density of vesicular GABA transporter in the mPFC of AOF females only. These findings suggest sex-specific changes in GABAergic neurons in the hippocampus and mPFC with males showing an increase of this cell population as compared to their female counterparts following CIH. Age at exposure and severity of CIH also differentially affect the GABAergic cell population in mice.

中文翻译：

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性别和年龄对慢性间歇性缺氧后小鼠前额叶皮层和海马中的GABA能神经元有不同的影响。

阻塞性睡眠呼吸暂停（OSA）是一种慢性睡眠障碍，其特征是在睡眠过程中反复减少或停止气流，广泛流行，并与不良的神经认知后遗症相关，包括增加了阿尔茨海默氏病（AD）的风险。在人类中，OSA在老年男性中更为常见。OSA的特征是睡眠破碎和慢性间歇性缺氧（CIH），最近的流行病学研究指出，CIH是与OSA相关的神经认知后遗症的最佳预测指标。与OSA相关的CIH的性别和年龄特异性作用对特定细胞群（如海马和认知功能重要区域的海马和前额叶皮层（mPFC）中的γ-氨基丁酸（GABA）-能神经元）的作用尚不清楚。本研究检查了35天的中度（10％氧气）或重度（5％氧气）CIH对成年和成年雄性和雌性小鼠的mPFC和海马中的GABA能神经元以及卵巢加速衰竭的影响（ AOF）雌性小鼠。在mPFC和海马中，与对照组相比，老年和年轻的重症CIH男性中GABA标记的神经元数量增加，而中度的CIH男性则没有。这种变化不能代表单个GABA能细胞亚群，因为仅重度CIH年轻男性海马中小白蛋白标记的神经元数量减少而生长抑素标记的神经元数量增加。在所有女性组中，CIH和对照组之间GABA标记的细胞数量没有差异。但是，在mPFC中，CIH增加了年轻女性中小白蛋白标记的神经元的数量和AOF女性中生长抑素标记的细胞的数量，但降低了老年女性中生长抑素标记的细胞的数量。在海马中，CIH减少了年轻女性中生长抑素标记的神经元的数量。CIH仅在AOF女性的mPFC中降低了水泡GABA转运蛋白的密度。这些发现表明，在海马和mPFC中，GABA能神经元的性别特异性改变与雄性相比，与CIH后的雌性相比，雄性显示出该细胞群的增加。暴露时的年龄和CIH的严重程度也会不同地影响小鼠的GABA能细胞群。CIH减少了年轻女性中生长抑素标记的神经元的数量。CIH仅在AOF女性的mPFC中降低了水泡GABA转运蛋白的密度。这些发现表明，在海马和mPFC中，GABA能神经元的性别特异性改变与雄性相比，与CIH后的雌性相比，雄性显示出该细胞群的增加。暴露时的年龄和CIH的严重程度也会不同地影响小鼠的GABA能细胞群。CIH减少了年轻女性中生长抑素标记的神经元的数量。CIH仅在AOF女性的mPFC中降低了水泡GABA转运蛋白的密度。这些发现表明，在海马和mPFC中，GABA能神经元的性别特异性改变与雄性相比，与CIH后的雌性相比，雄性显示出该细胞群的增加。暴露时的年龄和CIH的严重程度也会不同地影响小鼠的GABA能细胞群。