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Here, using an established model of acupuncture treatment in Parkinson's disease (PD) model mice, we show that peripheral acupuncture stimulation activates hypothalamic melanin\u2010concentrating hormone (MCH) neurons via nerve conduction. We further identify two separate neural pathways originating from anatomically and electrophysiologically distinct MCH neuronal subpopulations, projecting to the substantia nigra and hippocampus, respectively. Through chemogenetic manipulation specifically targeting these MCH projections, their respective roles in mediating the acupuncture\u2010induced motor recovery and memory improvements following PD onset are demonstrated, as well as the underlying mechanisms mediating recovery from dopaminergic neurodegeneration, reactive gliosis, and impaired hippocampal synaptic plasticity. Collectively, these MCH neurons constitute not only a circuit\u2010based explanation for the therapeutic effectiveness of traditional acupuncture, but also a potential cellular target for treating both motor and non\u2010motor PD symptoms.<\/jats:p>","DOI":"10.1002\/advs.202403245","type":"journal-article","created":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T07:36:15Z","timestamp":1723188975000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Central Role of Hypothalamic Circuits for Acupuncture's Anti\u2010Parkinsonian Effects"],"prefix":"10.1002","volume":"11","author":[{"given":"Ju\u2010Young","family":"Oh","sequence":"first","affiliation":[{"name":"College of Korean Medicine Kyung Hee University  Seoul 02447 Republic of Korea"},{"name":"Studies of Translational Acupuncture Research (STAR) Kyung Hee University  Seoul 02447 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyowon","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Korean Medicine Kyung Hee University  Seoul 02447 Republic of Korea"},{"name":"Brain Science Institute Korea Institute of Science and Technology (KIST)  Seoul 02792 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun\u2010Young","family":"Jang","sequence":"additional","affiliation":[{"name":"College of Korean Medicine Kyung Hee University  Seoul 02447 Republic of Korea"},{"name":"Studies of Translational Acupuncture Research (STAR) Kyung Hee University  Seoul 02447 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunjin","family":"Kim","sequence":"additional","affiliation":[{"name":"Brain Science Institute Korea Institute of Science and Technology (KIST)  Seoul 02792 Republic of Korea"},{"name":"Department of KHU\u2010KIST Convergence Science and Technology Kyung Hee University  Seoul 02447 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geunhong","family":"Park","sequence":"additional","affiliation":[{"name":"Brain Science Institute Korea Institute of Science and Technology (KIST)  Seoul 02792 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Almas","family":"Serikov","sequence":"additional","affiliation":[{"name":"Brain Science Institute Korea Institute of Science and Technology (KIST)  Seoul 02792 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae\u2010Hwan","family":"Jang","sequence":"additional","affiliation":[{"name":"Studies of Translational Acupuncture Research (STAR) Kyung Hee University  Seoul 02447 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyeop","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory of Stem Cells &amp; Cell Reprogramming Department of Chemistry Dongguk University  Seoul 04629 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seulkee","family":"Yang","sequence":"additional","affiliation":[{"name":"Brain Science Institute Korea Institute of Science and Technology (KIST)  Seoul 02792 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moonsun","family":"Sa","sequence":"additional","affiliation":[{"name":"Center for Cognition and Sociality Institute for Basic Science  Daejeon 34126 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Eun","family":"Lee","sequence":"additional","affiliation":[{"name":"Center for Cognition and Sociality Institute for Basic Science  Daejeon 34126 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young\u2010Eun","family":"Han","sequence":"additional","affiliation":[{"name":"Brain Science Institute Korea Institute of Science and Technology (KIST)  Seoul 02792 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae\u2010Yeon","family":"Hwang","sequence":"additional","affiliation":[{"name":"College of Korean Medicine Kyung Hee University  Seoul 02447 Republic of Korea"},{"name":"Studies of Translational Acupuncture Research (STAR) Kyung Hee University  Seoul 02447 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon Jiyoon","family":"Jung","sequence":"additional","affiliation":[{"name":"Technological Convergence Center Korea Institute of Science and Technology (KIST)  Seoul 02792 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Physiology Yonsei University  Seoul 03722 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Eun","family":"Lee","sequence":"additional","affiliation":[{"name":"Center for Cognition and Sociality Institute for Basic Science  Daejeon 34126 Republic of Korea"},{"name":"Research Animal Resource Center Korea Institute of Science and Technology (KIST)  Seoul 02792 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo\u2010Jin","family":"Oh","sequence":"additional","affiliation":[{"name":"Brain Science Institute Korea Institute of Science and Technology (KIST)  Seoul 02792 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeongjin","family":"Kim","sequence":"additional","affiliation":[{"name":"Brain Science Institute Korea Institute of Science and Technology (KIST)  Seoul 02792 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeongyeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Emotion, Cognition &amp; 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