Circulating messenger for neuroprotection induced by molecular hydrogen

Abstract

Molecular hydrogen (H2) showed protection against various kinds of oxidative stress- related diseases. First it was reported that the mechanism of therapeutic effects of H2 was anti-oxidative effect due to inhibition of most cytotoxic reactive oxygen species (ROS), hydroxy radical (•OH). However, after chronic administration of H2 in drinking water, oxidative stress-induced nerve injury is significantly attenuated even in the absence of H2. It suggests indirect signaling of H2 and gastrointestinal tract is involved. Indirect effects of H2 could be tested by giving H2 water only before nerve injury, as preconditioning. For example, preconditioning of H2 for certain period (~7 days) in Parkinson’s disease model mice shows significant neuroprotection. As the mechanism of indirect effect, H2 in drinking water induces ghrelin production and release from the stomach via β1-adrenergic receptor stimulation. Released ghrelin circulates in the body, being transported across the blood-brain barrier, activates its receptor, growth-hormone secretagogue receptor (GHSR). H2-induced upregulation of ghrelin mRNA is also shown in ghrelin-producing cell line, SG-1. These observations help understand the chronic effects of H2 and raise intriguing preventive and therapeutic options using H2. Key words: molecular hydrogen, preconditioning, Parkinson’s disease, ghrelin

Study details

Article type

Review

Disease / injury model

Parkinson’s disease

Dose comparison

The review describes that 7 days of preconditioning with hydrogen water (0.8-1.0 ppm) is necessary for significant neuroprotection, while shorter durations (1 or 3 days) are insufficient.

Dose-dependent effect

Yes

Outcome

Positive

Findings

Chronic administration of molecular hydrogen (H2) in drinking water provides neuroprotection against oxidative stress-induced nerve injury, particularly in Parkinson’s disease models, via an indirect mechanism involving increased ghrelin production and release from the stomach, which acts as a circulating messenger to the brain.