Oral ‘hydrogen water’ induces neuroprotective ghrelin secretion in mice

Abstract

The therapeutic potential of molecular hydrogen (H2) is emerging in a number of human diseases and in their animal models, including in particular Parkinson’s disease (PD). H2 supplementation of drinking water has been shown to exert disease-modifying effects in PD patients and neuroprotective effects in experimental PD model mice. However, H2 supplementation does not result in detectable changes in striatal H2 levels, indicating an indirect effect. Here we show that H2 supplementation increases gastric expression of mRNA encoding ghrelin, a growth hormone secretagogue, and ghrelin secretion, which are antagonized by the b1-adrenoceptor blocker, atenolol. Strikingly, the neuroprotective effect of H2 water was abolished by either administration of the ghrelin receptor-antagonist, D-Lys3 GHRP-6, or atenolol. Thus, the neuroprotective effect of H2 in PD is mediated by enhanced production of ghrelin. Our findings point to potential, novel strategies for ameliorating pathophysiology in which a protective effect of H2 supplementation has been demonstrated.

Study details

Article type

Original Research

Disease / injury model

MPTP-induced Parkinson's disease model in mice

Duration

7 days

Dose comparison

Hydrogen water was administered at concentrations ranging from 0.04 to 0.8 mM; neuroprotective and ghrelin-inducing effects were observed to be dose-independent within this range.

Dose-dependent effect

No

Outcome

Positive

Findings

Oral administration of hydrogen water in mice induces gastric ghrelin gene expression and secretion, which mediates neuroprotection in a Parkinson's disease model. The neuroprotective effect is dependent on b1-adrenergic receptor signaling and is abolished by ghrelin receptor antagonism or b1-blockade.