A mouse study looked at whether drinking hydrogen‑rich water protects against Parkinson‑like brain damage and whether the stomach hormone ghrelin (or its receptor) is needed for that protection. Even when ghrelin was missing or its receptor was blocked with a ghrelin‑receptor antagonist (D‑Lys³‑GHRP‑6), the hydrogen water still helped, suggesting other factors are at play.

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.