Central Role of Hypothalamic Circuits for Acupuncture's Anti-Parkinsonian Effects

Ju Young Oh, Hyowon Lee, Sun Young Jang, Hyunjin Kim, Geunhong Park, Almas Serikov, Jae Hwan Jang, Junyeop Kim, Seulkee Yang, Moonsun Sa, Sung Eun Lee, Young Eun Han, Tae Yeon Hwang, Sharon Jiyoon Jung, Hee Young Kim, Seung Eun Lee, Soo Jin Oh, Jeongjin Kim, Jeongyeon Kim, Jongpil KimThomas J. McHugh, C. Justin Lee, Min Ho Nam, Hi Joon Park

Research output: Contribution to journalArticlepeer-review

Abstract

Despite clinical data stretching over millennia, the neurobiological basis of the effectiveness of acupuncture in treating diseases of the central nervous system has remained elusive. Here, using an established model of acupuncture treatment in Parkinson's disease (PD) model mice, we show that peripheral acupuncture stimulation activates hypothalamic melanin-concentrating 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-induced 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-based explanation for the therapeutic effectiveness of traditional acupuncture, but also a potential cellular target for treating both motor and non-motor PD symptoms.

Original languageEnglish
Article number2403245
JournalAdvanced Science
Volume11
Issue number43
DOIs
StatePublished - 20 Nov 2024

Keywords

  • Parkinson's disease (PD)
  • acupuncture
  • hypothalamus
  • melanin-concentrating hormone (MCH)
  • motor and non-motor symptoms
  • neural circuitry

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