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.
摘要:
尽管临床数据延续了几千年,针灸治疗中枢神经系统疾病的有效性的神经生物学基础仍然难以捉摸。这里,使用已建立的帕金森病(PD)模型小鼠的针刺治疗模型,我们显示,周围针刺刺激通过神经传导激活下丘脑黑色素浓缩激素(MCH)神经元。我们进一步确定了源自解剖学和电生理学上不同的MCH神经元亚群的两个独立的神经通路。投射到黑质和海马体,分别。通过专门针对这些MCH预测的化学遗传学操作,证明了它们各自在介导PD发作后针刺诱导的运动恢复和记忆改善中的作用,以及介导多巴胺能神经变性恢复的潜在机制,反应性神经胶质增生,海马突触可塑性受损。总的来说,这些MCH神经元不仅构成了对传统针灸治疗效果的基于电路的解释,但也是治疗运动和非运动PD症状的潜在细胞靶标。