title: Novel Neuroprotective Effects of Melanin-Concentrating Hormone in Parkinson's Disease.
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.
authors.affiliation: Integrative Parkinson's Disease Research Group, Acupuncture & Meridian Science Research Center, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemoon-gu, Seoul, 02447, Republic of Korea.|College of Korean Medicine, Daejeon University, 62 Daehak-ro, Dong-gu, Daejeon, 34520, Republic of Korea.
authors.forename: Ji-Yeun
authors.initials: JY
authors.lastname: Park
authors.affiliation: Integrative Parkinson's Disease Research Group, Acupuncture & Meridian Science Research Center, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemoon-gu, Seoul, 02447, Republic of Korea.|Department of Meridian and Acupoint, Dongguk University, Dongguk-ro 32, Ilsandong-gu, Goyang-si, Gyeonggi-do, 10326, Republic of Korea.
authors.forename: Seung-Nam
authors.initials: SN
authors.lastname: Kim
authors.affiliation: Department of Biomedical Engineering, Dongguk University, 3-ga, Pil-dong, Chung-gu, Seoul, 04620, Republic of Korea.
authors.forename: Junsang
authors.initials: J
authors.lastname: Yoo
authors.affiliation: Integrative Parkinson's Disease Research Group, Acupuncture & Meridian Science Research Center, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemoon-gu, Seoul, 02447, Republic of Korea.
authors.forename: Jaehwan
authors.initials: J
authors.lastname: Jang
authors.affiliation: Integrative Parkinson's Disease Research Group, Acupuncture & Meridian Science Research Center, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemoon-gu, Seoul, 02447, Republic of Korea.|Department of Korean Medical Science, Graduate School of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemoon-gu, Seoul, 02447, Republic of Korea.
authors.forename: Ahreum
authors.initials: A
authors.lastname: Lee
authors.affiliation: Integrative Parkinson's Disease Research Group, Acupuncture & Meridian Science Research Center, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemoon-gu, Seoul, 02447, Republic of Korea.|Department of Korean Medical Science, Graduate School of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemoon-gu, Seoul, 02447, Republic of Korea.
authors.forename: Ju-Young
authors.initials: JY
authors.lastname: Oh
authors.affiliation: Department of Biomedical Engineering, Dongguk University, 3-ga, Pil-dong, Chung-gu, Seoul, 04620, Republic of Korea.
authors.forename: Hongwon
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Biomedical Engineering, Dongguk University, 3-ga, Pil-dong, Chung-gu, Seoul, 04620, Republic of Korea.
authors.forename: Seung Tack
authors.initials: ST
authors.lastname: Oh
authors.affiliation: Integrative Parkinson's Disease Research Group, Acupuncture & Meridian Science Research Center, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemoon-gu, Seoul, 02447, Republic of Korea.|Stroke and Neurological Disorders Center, Kyung Hee University Hospital at Gangdong, Seoul, 05278, Republic of Korea.
authors.forename: Seong-Uk
authors.initials: SU
authors.lastname: Park
authors.affiliation: Department of Biomedical Engineering, Dongguk University, 3-ga, Pil-dong, Chung-gu, Seoul, 04620, Republic of Korea. jk2316@gmail.com.
authors.forename: Jongpil
authors.initials: J
authors.lastname: Kim
authors.affiliation: Integrative Parkinson's Disease Research Group, Acupuncture & Meridian Science Research Center, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemoon-gu, Seoul, 02447, Republic of Korea. acufind@khu.ac.kr.|Department of Korean Medical Science, Graduate School of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemoon-gu, Seoul, 02447, Republic of Korea. acufind@khu.ac.kr.
authors.forename: Hi-Joon
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Department of Biomedical Sciences, Center for Creative Biomedical Scientists, Chonnam National University, Gwangju, 61469, Republic of Korea. jsong0304@hanmail.net.
authors.forename: Songhee
authors.initials: S
authors.lastname: Jeon
mesh_terms: D015670:Acupuncture Therapy / Q000379:methods*; D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D007028:Hypothalamic Hormones / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D008543:Melanins / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018696:Neuroprotective Agents / Q000378:metabolism*; D020734:Parkinsonian Disorders / Q000378:metabolism* / Q000517:prevention & control*; D010907:Pituitary Hormones / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D016896:Treatment Outcome
chemical_list: D007028:Hypothalamic Hormones; D008543:Melanins; D018696:Neuroprotective Agents; D010907:Pituitary Hormones; C019463:melanin-concentrating hormone
keywords: Acupuncture; Dopamine neuroprotection; Lateral hypothalamus; Melanin-concentrating hormone (MCH); Parkinson’s disease