Physical Activity Attenuates Intermittent Hypoxia-induced Spatial Learning Deficits and Oxidative Stress
Physical Activity Attenuates Intermittent Hypoxia-induced Spatial Learning Deficits and Oxidative Stress
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DOI：
10.1164/rccm.201001-0108oc
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发表时间：
2010-07-01
影响因子：
24.7
通讯作者：
Goldbart, Aviv D.
中科院分区：
文献类型：
--
作者：
Gozal, David;Nair, Deepti;Goldbart, Aviv D.
理由-暴露于间歇性缺氧（IH），如发生在睡眠呼吸障碍，与实质性的认知障碍，氧化应激和炎症，并增加神经元细胞损失的大脑区域的基础学习和记忆在大鼠。在神经元损伤和变性的模型中，体力活动（PA）现在被认为是神经保护的。目的：研究PA是否会改善IH诱导的缺陷。将年轻成年Sprague-Dawley大鼠随机分为正常活动（NA）或PA 4个治疗组，持续3个月，然后进行常氧（RA）测量和主要结果：暴露于IH的大鼠在水迷宫中定位隐藏平台的潜伏期和路径长度均出现显著损伤，并且在探测试验中空间偏差降低。在PA-IH大鼠中未观察到这些损伤。此外，PA-IH组，相对于NA-IH，赋予更大的抵抗脂质过氧化和8羟基-2 '-脱氧鸟苷（DNA损伤）在皮层和海马。在PA的神经保护作用的支持，PA-IH与NA-IH大鼠表现出更大的AKT激活和神经元胰岛素生长因子-1在这些regions.Conclusions：行为的修改，如增加体力活动与IH诱导的空间任务缺陷的敏感性降低，并导致氧化应激减少，可能通过改善胰岛素生长因子-1 Akt神经元信号的保存。考虑到PA的许多优点，应在睡眠呼吸障碍患者中寻求针对导致PA增加的行为改变的干预策略。
Rationale-. Exposure to intermittent hypoxia (IH), such as occurs in sleep-disordered breathing, is associated with substantial cognitive impairments, oxidative stress and inflammation, and increased neuronal cell losses in brain regions underlying learning and memory in rats. Physical activity (PA) is now recognized as neuroprotective in models of neuronal injury and degeneration.Objectives: To examine whether PA will ameliorate IH-induced deficits.Methods: Young adult Sprague-Dawley rats were randomly assigned to one of four treatment groups including normal activity (NA) or PA for 3 months and then subjected to either normoxia (RA) or exposure to IH during the light phase during the last 14 days.Measurements and Main Results: Significant impairments in IH-exposed rats emerged on both latency and pathlength to locate the hidden platform in a water maze and decreased spatial bias during the probe trials. These impairments were not observed in PA-IH rats. In addition, the PA-IH group, relative to NA-IH, conferred greater resistance to both lipid peroxidation and 8hydroxy-2'-deoxyguanosine (DNA damage) in both the cortex and hippocampus. In support of a neuroprotective effect from PA, PA-IH versus NA-IH rats showed greater AKT activation and neuronal insulin growth factor-1 in these regions.Conclusions: Behavioral modifications such as increased physical activity are associated with decreased susceptibility to IH-induced spatial task deficits and lead to reduced oxidative stress, possibly through improved preservation of insulin growth factor-1 Akt neuronal signaling. Considering the many advantages of PA, interventional strategies targeting behavioral modifications leading to increased PA should be pursued in patients with sleep-disordered breathing.