Adverse cognitive effects of high-fat diet in a murine model of sleep apnea are mediated by NADPH oxidase activity.
Adverse cognitive effects of high-fat diet in a murine model of sleep apnea are mediated by NADPH oxidase activity.
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DOI：
10.1016/j.neuroscience.2012.09.068
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发表时间：
2012-12-27
期刊：
影响因子：
3.3
通讯作者：
Gozal, D.
中科院分区：
文献类型：
--
作者：
Nair, D.;Ramesh, V.;Gozal, D.
睡眠期间的间歇性缺氧（IH），比如在睡眠呼吸暂停（SA）中出现的情况，会诱导烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶活化增加以及海马学习和记忆能力下降。与IH类似，高脂肪 - 精制碳水化合物饮食（HFD）在睡眠呼吸暂停患者中经常出现，在常氧条件下也能诱导类似的氧化应激和认知缺陷，这表明NADPH氧化酶活性过高可能是这两种情况下中枢神经系统（CNS）功能障碍的原因。在缺乏NADPH氧化酶活性的雄性小鼠（gp91phox - /Y）和喂食高脂肪饮食的野生型同窝小鼠中，评估了光照期间高脂肪饮食和间歇性缺氧对水迷宫中两种空间学习形式以及氧化应激标志物的影响。在标准位置训练任务中，gp91phox - /Y表现出正常的学习能力，并且免受暴露于间歇性缺氧的野生型同窝小鼠所出现的空间学习缺陷的影响。此外，与对照组相比，暴露于高脂肪饮食和间歇性缺氧的野生型小鼠的焦虑水平升高，而gp91phox - /Y小鼠则没有变化。此外，在间歇性缺氧 - 高脂肪饮食暴露后，野生型小鼠（而非gp91phox - /Y小鼠）的海马裂解物中丙二醛（MDA）和8 - 羟基脱氧鸟苷（8 - OHdG）水平显著升高。肥胖和西方化饮食以及以睡眠期间间歇性缺氧为特征的睡眠障碍所导致的认知缺陷，至少在一定程度上都是由NADPH氧化酶活性过高所介导的。
Intermittent hypoxia (IH) during sleep, such as occurs in sleep apnea (SA), induces increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation and deficits in hippocampal learning and memory. Similar to IH, high fat-refined carbohydrate diet (HFD), a frequent occurrence in patients with SA, can also induce similar oxidative stress and cognitive deficits under normoxic conditions, suggesting that excessive NADPH oxidase activity may underlie central nervous system (CNS) dysfunction in both conditions. The effect of HFD and IH during the light period on two forms of spatial learning in the water maze as well as on markers of oxidative stress was assessed in male mice lacking NADPH oxidase activity (gp91phox-/Y) and wild-type littermates fed HFD. On a standard place training task, gp91phox_/Y displayed normal learning, and was protected from the spatial learning deficits observed in wild-type littermates exposed to IH. Moreover, anxiety levels were increased in wild-type mice exposed to HFD and IH as compared to controls, while no changes emerged in gp91phox_/Y mice. Additionally, wild-type mice, but not gp91phox_/Y mice, had significantly elevated levels of malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG) in hippocampal lysates following IH-HFD exposures. The cognitive deficits of obesity and westernized diets and those of sleep disorders that are characterized by IH during sleep are both mediated, at least in part, by excessive NADPH oxidase activity.
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