Neurochemical Research

, Volume 42, Issue 9, pp 2658–2665 | Cite as

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

  • Yusuke Yoshii
  • Taikai Inoue
  • Yuya Uemura
  • Yusaku Iwasaki
  • Toshihiko Yada
  • Yusaku Nakabeppu
  • Mami NodaEmail author
Original Paper


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.


Molecular hydrogen Parkinson’s disease Ghrelin Vagal afferents Ghrelin-knock out mice 



We thank Prof. David A. Brown (UCL, UK) for reading the manuscript and Prof. Fusao Kato (Jikei University, Japan) for providing useful comments. We thank Prof. Masayasu Kojima and Dr. Takahiro Sato (Kurume University, Japan) for supplying us ghrelin-KO mice. We also thank Miss Megumi Yamafuji (Graduate School of Pharmaceutical Science, Kyushu University, Japan), Dr. Hiroko Nomaru (Medical Institute of Bioregulation, Kyushu University, Japan) for helping some of the experiments. This work was partly supported by Laboratory for Technical Supports Medical Institute of Bioregulation and the Research Support Center, Graduate School of Medical Sciences, Kyushu University.

Compliance with Ethical Standards

Conflict of interest

The authors declare no conflict of interest associated with this manuscript.


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Yusuke Yoshii
    • 1
  • Taikai Inoue
    • 1
  • Yuya Uemura
    • 1
  • Yusaku Iwasaki
    • 2
  • Toshihiko Yada
    • 2
  • Yusaku Nakabeppu
    • 3
  • Mami Noda
    • 1
    Email author
  1. 1.Laboratory of Pathophysiology, Graduate School of Pharmaceutical SciencesKyushu UniversityFukuokaJapan
  2. 2.Division of Integrative Physiology, Department of PhysiologyJichi Medical University School of MedicineShimotsukeJapan
  3. 3.Division of Neurofunctional Genomics, Medical Institute of BioregulationKyushu UniversityFukuokaJapan

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