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

Abstract

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 mM 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 0 -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.

Effect of Molecular Hydrogen Saturated Alkaline Electrolyzed Water on Disuse Muscle Atrophy in Gastrocnemius Muscle

“…Therefore, we would have to consider that ingestion of HSW in this HU model is not a likely promising agent for a therapeutic antioxidant to suppress oxidative stress during HU and progression of disuse muscle atrophy. However, considering previous evidence in animal studies that drinking H 2 -saturated water ad libitum reduces oxidative stress (Nagata et al, 2008;Ohsawa et al, 2008;Sato et al, 2008), our results, such as the trend toward suppression of 8-OHdG and SOD-like activity in HSW, suggest something that we cannot ignore. We observed that H 2 concentrations of both AEW and HSW had plunged to nearly one-half after one day.…”

Neuroprotective effects of hydrogen saline in neonatal hypoxia–ischemia rat model

“…ONOO − also reacts with carbon dioxide (CO2) present in biological fluids to form reactive intermediates that can oxidize thiols and nitrate phenolic compounds, such as tyrosine (Valko et al, 2007 Fukuda et al, 2007). They also found that inhalation of hydrogen gas reduced infarct size in the rat model of myocardial ischemia-reperfusion injury (Hayashida et al, 2008) and intragastric administration of H 2 saline prevented the stress-induced decline in learning and memory caused by chronic physical restraint (Nagata et al, 2008). …”

“…It is established that hydrogen at a concentration above 4% is inflammable and dangerous, and application of hydrogen gas requires either a sealed chamber or mask. In a previous study that hydrogen water was administered into the stomach of rats (Nagata et al, 2008). Even though this gastric administration is safe, but hydrogen in water tends to evaporate and loss hydrogen in the stomach or intestine, and it is difficult to control concentration and absorption.…”

Protective effect of hydrogen-rich saline on ischemia/reperfusion injury in rat skin flap

“…H 2 was reported as a new antioxidant and a selective scavenger of ·OH effective in various organs (Nagata et al, 2009;Zheng et al, 2009;Sun et al, 2011). H 2 can convert hydroxyl into water (H 2 +·OH →H 2 O+·H).…”