南京大学朱景宁等研究人员合作发现，组胺能神经支配的丘脑腹前核缓解6-OHDA诱导的帕金森病大鼠运动缺陷。相关论文于2024年12月2日在线发表在《神经科学通报》杂志上。

研究人员评估了组胺对丘脑腹前核（VA）神经元活动和帕金森病（PD）运动缺陷的贡献。功能磁共振成像显示PD患者的VA活动减少。对VA神经元或组胺能传入神经的光遗传学激活，显著缓解了6-OHDA诱导的PD大鼠的运动缺陷。

此外，组胺通过H1和H2受体及其偶联的超极化激活环核苷酸门控通道、内向整流K⁺通道或Ca²⁺激活的K⁺通道激活VA神经元。这些结果表明，组胺能传入神经通过偏向VA活动积极补偿帕金森运动缺陷。这些发现提示，靶向VA组胺受体及其下游离子通道可能是治疗PD运动功能障碍的潜在策略。

据悉，VA是基底神经节的主要靶点，且与PD的发病机制密切相关。值得注意的是，VA直接接受来自下丘脑组胺能系统的神经支配。然而，组胺在PD中的作用尚不清楚。

附：英文原文

Title: Histaminergic Innervation of the Ventral Anterior Thalamic Nucleus Alleviates Motor Deficits in a 6-OHDA-Induced Rat Model of Parkinson’s Disease

Author: Xu, Han-Ting, Xi, Xiao-Ya, Zhou, Shuang, Xie, Yun-Yong, Cui, Zhi-San, Zhang, Bei-Bei, Xie, Shu-Tao, Li, Hong-Zhao, Zhang, Qi-Peng, Pan, Yang, Zhang, Xiao-Yang, Zhu, Jing-Ning

Issue&Volume: 2024-12-02

Abstract: The ventral anterior (VA) nucleus of the thalamus is a major target of the basal ganglia and is closely associated with the pathogenesis of Parkinson’s disease (PD). Notably, the VA receives direct innervation from the hypothalamic histaminergic system. However, its role in PD remains unknown. Here, we assessed the contribution of histamine to VA neuronal activity and PD motor deficits. Functional magnetic resonance imaging showed reduced VA activity in PD patients. Optogenetic activation of VA neurons or histaminergic afferents significantly alleviated motor deficits in 6-OHDA-induced PD rats. Furthermore, histamine excited VA neurons via H1 and H2 receptors and their coupled hyperpolarization-activated cyclic nucleotide-gated channels, inward-rectifier K+ channels, or Ca2+-activated K+ channels. These results demonstrate that histaminergic afferents actively compensate for Parkinsonian motor deficits by biasing VA activity. These findings suggest that targeting VA histamine receptors and downstream ion channels may be a potential therapeutic strategy for PD motor dysfunction.

DOI: 10.1007/s12264-024-01320-0

Source: https://link.springer.com/article/10.1007/s12264-024-01320-0