Abstract
The inability to successfully adapt to stress produces pathological changes that can lead to depression. Molecular hydrogen has anti-oxidative and anti-inflammatory activities and neuroprotective effects. However, the potential role of molecular hydrogen in stress-related disorders is still poorly understood. The present study aims to investigate the effects of hydrogen gas on resilience to stress in mice. The results showed that repeated inhalation of hydrogen-oxygen mixed gas [67%:33% (V/V)] significantly decreased both the acute and chronic stress-induced depressive- and anxiety-like behaviors of mice, assessed by tail suspension test (TST), forced swimming test (FST), novelty suppressed feeding (NSF) test, and open field test (OFT). ELISA analyses showed that inhalation of hydrogen-oxygen mixed gas blocked CMS-induced increase in the serum levels of corticosterone, adrenocorticotropic hormone, interleukin-6, and tumor necrosis factor-α in mice exposed to chronic mild stress. Finally, inhalation of hydrogen gas in adolescence significantly increased the resilience to acute stress in early adulthood, which illustrates the long-lasting effects of hydrogen on stress resilience in mice. This was likely mediated by inhibiting the hypothalamic-pituitary-adrenal axis and inflammatory responses to stress. These results warrant further exploration for developing molecular hydrogen as a novel strategy to prevent the occurrence of stress-related disorders.
Highlights
Stress-related disorders, such as depression and anxiety, are the most common and debilitating psychiatric diseases around the world[1]
In the current study, using acute and chronic stress mice model, we explored the potential effects of molecular hydrogen on behavioural changes in response to stress in adult mice
We found that repeated inhalation of hydrogen gas enhanced resilience of mice subjected to acute or chronic stress by blocking the normal stress-induced depressive-and anxiety-like behaviours
Summary
Stress-related disorders, such as depression and anxiety, are the most common and debilitating psychiatric diseases around the world[1]. Increasing evidence from animal and human studies indicate that molecular hydrogen offers significant neuroprotective effects in neuropathic pain, Parkinson’s disease, Alzheimer’s disease, and brain injury via alleviating excessive inflammatory response and oxidative stress[27, 29,30,31] These neurological benefits may be mediated by second messenger systems such as H2-induced neuroprotective gastric ghrelin secretion[32]. Zhang and colleagues reported that hydrogen-rich water had antidepressant-like effects in CMS-treated mice by inhibiting oxidative stress, inflammation and apoptosis in the hippocampus and prefrontal cortex[35] These studies strongly suggest that hydrogen, as a potential preventive and/ or therapeutic molecule, has beneficial effects on resilience to stress and even to stress-related disorders including depression and anxiety. We assessed the HPA activity and immune response by measuring the serum levels of corticosterone (CORT), adrenocorticotropic hormone (ACTH), IL-6 and TNF-α to elucidate the potential mechanism(s) of hydrogen using a chronic mild stress (CMS) mouse model
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