MCHR1 in Both Dopaminergic Neurons and Astrocytes in the SNpc Contributes to Acupuncture's Anti-Parkinsonian Effects.

Acupuncture stimulation at the GB34 acupoint has been reported to alleviate motor dysfunction in Parkinson's disease (PD) by activating the lateral hypothalamic melanin concentrating hormone (MCH) neurons projecting to the substantia nigra pars compacta (SNpc). MCH receptor 1 (MCHR1) signaling is also known to be essential for the anti-Parkinsonian effects of acupuncture. However, the cellular distribution of MCHR1 and its cell type-specific contributions to the therapeutic effects of acupuncture in PD remain largely unexplored. Here, we show that MCHR1 is expressed in both dopaminergic neurons and astrocytes within the SNpc, with higher expression in dopaminergic neurons. We further demonstrate that cell-type-specific gene-silencing of MCHR1 in either dopaminergic neurons or astrocytes significantly blocks acupuncture-induced motor recovery and dopaminergic neuron protection. These findings indicate that both neuronal and astrocytic MCHR1 contribute to the anti-Parkinsonian effects of acupuncture. Together, this study provides new insight into MCHR1 as a potential therapeutic target for PD.