Department of Pediatrics, Pritzker School of Medicine, The University of Chicago, Chicago, IL, United States.
Neuroscience. 2012 Dec 27;227:361-9. doi: 10.1016/j.neuroscience.2012.09.068. Epub 2012 Oct 11.
Intermittent hypoxia (IH) during sleep, such as occurs in sleep apnea (SA), induces increased 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 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 on 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.
间歇性低氧（IH），如在睡眠呼吸暂停（SA）中发生的，会导致 NADPH 氧化酶激活增加和海马学习记忆缺陷。与 IH 类似，高脂肪精制碳水化合物饮食（HFD），在 SA 患者中经常发生，也可以在常氧条件下诱导类似的氧化应激和认知缺陷，这表明过多的 NADPH 氧化酶活性可能是这两种情况中枢神经系统功能障碍的基础。在雄性小鼠中评估了 HFD 和 IH 在光期对水迷宫中两种形式的空间学习以及氧化应激标志物的影响，这些小鼠缺乏 NADPH 氧化酶活性（gp91phox⁻/Y），并且喂食 HFD 的野生型同窝仔。在标准位置训练任务中，gp91phox⁻/Y 显示出正常的学习能力，并且免受暴露于 IH 的野生型同窝仔中观察到的空间学习缺陷的影响。此外，与对照组相比，暴露于 HFD 和 IH 的野生型小鼠的焦虑水平升高，而 gp91phox⁻/Y 小鼠没有变化。此外，只有野生型小鼠，而不是 gp91phox⁻/Y 小鼠，在 IH-HFD 暴露后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。肥胖和西式饮食的认知缺陷以及以睡眠期间 IH 为特征的睡眠障碍的认知缺陷，至少部分是由过多的 NADPH 氧化酶活性介导的。
