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

Abstract

Molecular hydrogen (H), 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 H (H 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 H-induced ghrelin more precisely. To confirm the contribution of ghrelin in H water-drinking PD model mice, ghrelin-knock out (KO) mice were used. Despite the speculation, the effect of H 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 H water and administration of MPTP (1-methyl- 4-phenyl-1,2,3,6-tetrahydropyridine). The protective effect of H water was still observed in the vagotomized mice in substantia nigra, suggesting that stimulation of vagal afferent nerves is not involved in H-induced neuroprotection. Other neuroprotective substitutes in ghrelin-KO mice were speculated because H-induced neuroprotection was not cancelled by ghrelin receptor antagonist, D-Lys 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 H-induced neuroprotection and other factors can substitute the role of ghrelin when ghrelin is absent, raising intriguing options of research for H-responsive factors.

Dissecting the Role of Subtypes of Gastrointestinal Vagal Afferents

“…Both SDV and SDA are well-established techniques in rat, however, there are less studies using these techniques in mouse models. Mice undergoing bilateral SDV have been shown to survive for at least two weeks post-surgery (Iwasaki et al, 2015;Yoshii et al, 2017). However, a study has reported the lethality of this procedure in mice due to gastric distension and pyloric stenosis (Dezfuli et al, 2018).…”

<p>The Effects of 24-Week, High-Concentration Hydrogen-Rich Water on Body Composition, Blood Lipid Profiles and Inflammation Biomarkers in Men and Women with Metabolic Syndrome: A Randomized Controlled Trial</p>

“…22 However, the mechanism appears more complicated since the protective effects of HRW were still observed in a ghrelin-KO mice model of Parkinson's disease. 23 Nevertheless, it appears that a higher concentration of H 2 is at least as effective as, and often more effective than, a lower H 2 concentration. For example, it has been demonstrated that high-concentration hydrogen produced via magnesium was more effective than lowconcentration H 2 contained in alkaline ionized water in attenuating non-alcoholic fatty liver disease (NAFLD) in mice fed a high-fat diet.…”

Recent advances in the neuroprotective effects of medical gases

“…In a rat model of subarachnoid hemorrhage, injection of H 2 saline inhibits the nuclear factor-kappa B pathway and the nucleotide binding and oligomerization domain-like receptor family pyrin domain–containing three inflammasomes, which subsequently reduces the systemic inflammatory response and promotes the neurological function, as well as behavioural recovery 31. Yoshii et al38 reported that the observed neuroprotective effect of drinking hydrogen water could be associated with the secretion of ghrelin, a gastric hormone, in the stomach. However, the mechanism of H 2 appears to differ between the various experimental models.…”