Consumption of Molecular Hydrogen Prevents the Stress-Induced Impairments in Hippocampus-Dependent Learning Tasks during Chronic Physical Restraint in Mice

Consumption of Molecular Hydrogen Prevents the Stress-Induced Impairments in Hippocampus-Dependent Learning Tasks during Chronic Physical Restraint in Mice
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DOI:
10.1038/npp.2008.95
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发表时间:
2009-01-01
影响因子:
7.6
通讯作者:
Ohta, Shigeo
Ohta, Shigeo
中科院分区:
医学1区
文献类型:
--
作者:
Nagata, Kazufumi;Nakashima-Kamimura, Naomi;Ohta, Shigeo

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我们已经报道了氢(H-2)作为一种有效的抗氧化剂通过气体快速扩散。当将氢饱和的水(氢水)放入大鼠胃中时,在血液中检测到几μ M水平的氢。由于氢气不适合持续消耗,我们使用小鼠研究了自由饮用氢水而不是吸入氢气是否通过减少氧化应激来预防认知障碍。通过三种不同的方法:被动回避学习、物体识别任务和Morris水迷宫,对小鼠进行慢性物理束缚应激,增强了大脑中氧化应激标志物丙二醛和4-羟基-2-壬烯醛的水平,并损害了学习和记忆。在整个过程中随意饮用氢水抑制了氧化应激标志物的增加,并防止认知障碍,这三种方法都可以判断,而当没有压力时,氢水并没有改善认知能力。通过5-溴-2 '-脱氧尿苷掺入和增殖标记物Ki-67免疫染色观察到,束缚应激抑制海马齿状回的神经增殖。氢水的消耗改善了减少的增殖,尽管神经发生和认知障碍中的氢依赖性变化之间的机制联系尚不清楚。因此,持续消耗氢水可以减少大脑中的氧化应激,并防止由慢性身体约束引起的学习和记忆力下降。氢水可能适用于认知或其他神经元疾病的预防性使用。
We have reported that hydrogen (H-2) acts as an efficient antioxidant by gaseous rapid diffusion. When water saturated with hydrogen ( hydrogen water) was placed into the stomach of a rat, hydrogen was detected at several mu M level in blood. Because hydrogen gas is unsuitable for continuous consumption, we investigated using mice whether drinking hydrogen water ad libitum, instead of inhaling hydrogen gas, prevents cognitive impairment by reducing oxidative stress. Chronic physical restraint stress to mice enhanced levels of oxidative stress markers, malondialdehyde and 4-hydroxy-2-nonenal, in the brain, and impaired learning and memory, as judged by three different methods: passive avoidance learning, object recognition task, and the Morris water maze. Consumption of hydrogen water ad libitum throughout the whole period suppressed the increase in the oxidative stress markers and prevented cognitive impairment, as judged by all three methods, whereas hydrogen water did not improve cognitive ability when no stress was provided. Neural proliferation in the dentate gyrus of the hippocampus was suppressed by restraint stress, as observed by 5-bromo-2'-deoxyuridine incorporation and Ki-67 immunostaining, proliferation markers. The consumption of hydrogen water ameliorated the reduced proliferation although the mechanistic link between the hydrogen-dependent changes in neurogenesis and cognitive impairments remains unclear. Thus, continuous consumption of hydrogen water reduces oxidative stress in the brain, and prevents the stress-induced decline in learning and memory caused by chronic physical restraint. Hydrogen water may be applicable for preventive use in cognitive or other neuronal disorders.