黑质多巴胺信号及其对运动功能的影响——并非新概念,而是被忽视的现实。
Dopamine Signaling in Substantia Nigra and Its Impact on Locomotor Function-Not a New Concept, but Neglected Reality.
机构信息
Department of Pharmacology & Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
出版信息
Int J Mol Sci. 2024 Jan 17;25(2):1131. doi: 10.3390/ijms25021131.
The mechanistic influences of dopamine (DA) signaling and impact on motor function are nearly always interpreted from changes in nigrostriatal neuron terminals in striatum. This is a standard practice in studies of human Parkinson's disease (PD) and aging and related animal models of PD and aging-related parkinsonism. However, despite dozens of studies indicating an ambiguous relationship between changes in striatal DA signaling and motor phenotype, this perseverating focus on striatum continues. Although DA release in substantia nigra (SN) was first reported almost 50 years ago, assessment of nigral DA signaling changes in relation to motor function is rarely considered. Whereas DA signaling has been well-characterized in striatum at all five steps of neurotransmission (biosynthesis and turnover, storage, release, reuptake, and post-synaptic binding) in the nigrostriatal pathway, the depth of such interrogations in the SN, outside of cell counts, is sparse. However, there is sufficient evidence that these steps in DA neurotransmission in the SN are operational and regulated autonomously from striatum and are present in human PD and aging and related animal models. To complete our understanding of how nigrostriatal DA signaling affects motor function, it is past time to include interrogation of nigral DA signaling. This brief review highlights evidence that changes in nigral DA signaling at each step in DA neurotransmission are autonomous from those in striatum and changes in the SN alone can influence locomotor function. Accordingly, for full characterization of how nigrostriatal DA signaling affects locomotor activity, interrogation of DA signaling in SN is essential.
多巴胺(DA)信号的机制影响及其对运动功能的影响几乎总是通过纹状体中黑质纹状体神经元末梢的变化来解释。这是研究人类帕金森病(PD)和衰老以及相关 PD 和衰老相关帕金森病动物模型的标准做法。然而,尽管有数十项研究表明纹状体 DA 信号变化与运动表型之间存在模糊关系,但这种对纹状体的持续关注仍在继续。尽管 50 年前就首次报道了黑质中 DA 的释放,但很少考虑与运动功能相关的黑质 DA 信号变化的评估。虽然 DA 信号在黑质纹状体通路的神经传递的所有五个步骤(生物合成和周转率、储存、释放、再摄取和突触后结合)中在纹状体中得到了很好的描述,但在 SN 中对这些步骤的深入研究很少,除了细胞计数之外。然而,有足够的证据表明,SN 中的这些 DA 神经传递步骤是可操作的,并且可以独立于纹状体进行调节,并且存在于人类 PD 和衰老以及相关动物模型中。为了全面了解黑质纹状体 DA 信号如何影响运动功能,现在是时候包括对黑质 DA 信号的检测了。这篇简短的综述强调了证据表明,DA 神经传递中每个步骤的黑质 DA 信号变化与纹状体中的变化是自主的,并且 SN 中的变化本身就可以影响运动功能。因此,为了全面描述黑质纹状体 DA 信号如何影响运动活动,对 SN 中的 DA 信号检测是必不可少的。