Novel Neuroprotective Effects of Melanin-Concentrating Hormone in Parkinson’s Disease

Ji Yeun Park, Seung Nam Kim, Junsang Yoo, Jaehwan Jang, Ahreum Lee, Ju Young Oh, Hongwon Kim, Seung Tack Oh, Seong Uk Park, Jongpil Kim, Hi Joon Park, Songhee Jeon

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Acupuncture has shown the therapeutic effect on various neurodegenerative disorders including Parkinson’s disease (PD). While investigating the neuroprotective mechanism of acupuncture, we firstly found the novel function of melanin-concentrating hormone (MCH) as a potent neuroprotective candidate. Here, we explored whether hypothalamic MCH mediates the neuroprotective action of acupuncture. In addition, we aimed at evaluating the neuroprotective effects of MCH and elucidating underlying mechanism in vitro and in vivo PD models. First, we tested whether hypothalamic MCH mediates the neuroprotective effects of acupuncture by challenging MCH-R1 antagonist (i.p.) in mice PD model. We also investigated whether MCH has a beneficial role in dopaminergic neuronal protection in vitro primary midbrain and human neuronal cultures and in vivo MPTP-induced, Pitx3−/−, and A53T mutant mice PD models. Transcriptomics followed by quantitative PCR and western blot analyses were performed to reveal the neuroprotective mechanism of MCH. We first found that hypothalamic MCH biosynthesis was directly activated by acupuncture treatment and that administration of an MCH-R1 antagonist reverses the neuroprotective effects of acupuncture. A novel finding is that MCH showed a beneficial role in dopaminergic neuron protection via downstream pathways related to neuronal survival. This is the first study to suggest the novel neuroprotective action of MCH as well as the involvement of hypothalamic MCH in the acupuncture effects in PD, which holds great promise for the application of MCH in the therapy of neurodegenerative diseases.

Original languageEnglish
Pages (from-to)7706-7721
Number of pages16
JournalMolecular Neurobiology
Volume54
Issue number10
DOIs
StatePublished - 1 Dec 2017

Keywords

  • Acupuncture
  • Dopamine neuroprotection
  • Lateral hypothalamus
  • Melanin-concentrating hormone (MCH)
  • Parkinson’s disease

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