Complexity of Stomach–Brain Interaction Induced by Molecular Hydrogen in Parkinson’s Disease Model Mice

Abstract

Molecular hydrogen (H2), as a new medical gas, has protective effects in neurological disorders including Parkinson’s disease (PD). In our previous report, the neuroprotective effect of drinking water with saturated H2 (H2 water) in PD mice might be due to stomach–brain interaction via release of gastric hormone, ghrelin. In the present study, we assessed the effect of H2-induced ghrelin more precisely. To confirm the contribution of ghrelin in H2 water-drinking PD model mice, ghrelin-knock out (KO) mice were used. Despite the speculation, the effect of H2 water was still observed in ghrelin-KO PD model mice. To further check the involvement of ghrelin, possible contribution of ghrelin-induced vagal afferent effect was tested by performing subdiaphragmatic vagotomy before treating with H2 water and administration of MPTP (1-methyl- 4-phenyl-1,2,3,6-tetrahydropyridine). The protective effect of H2 water was still observed in the vagotomized mice in substantia nigra, suggesting that stimulation of vagal afferent nerves is not involved in H2-induced neuroprotection. Other neuroprotective substitutes in ghrelin-KO mice were speculated because H2-induced neuroprotection was not cancelled by ghrelin receptor antagonist, D-Lys3 GHRP-6, in ghrelin-KO PD model mice, unlike in wild-type PD model mice. Our results indicate that ghrelin may not be the only factor for H2-induced neuroprotection and other factors can substitute the role of ghrelin when ghrelin is absent, raising intriguing options of research for H2-responsive factors.

Study details

Article type

Original Research

Disease / injury model

MPTP-induced Parkinson’s disease mouse model

Duration

21 days

Dose comparison

No explicit dose/concentration comparison was performed; all groups received saturated H2 water (0.8 ppm) ad libitum.

Dose-dependent effect

No

Outcome

Positive

Findings

Oral administration of hydrogen-rich water provided neuroprotection in a mouse model of Parkinson’s disease, even in the absence of ghrelin or after vagotomy, suggesting that ghrelin is not the sole mediator of H2-induced neuroprotection and that other compensatory mechanisms exist.