Zhou Fu-Ming
Department of Pharmacology, Addiction Science and Toxicology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Diagnostics (Basel). 2025 Jun 5;15(11):1436. doi: 10.3390/diagnostics15111436.
Clinicopathological studies and the effectiveness of dopaminergic replacement therapy establish that dopamine loss is the key pathology causing motor symptoms in Parkinson's disease. The dopamine neurons that are impaired in Parkinson's disease reside in the substantia nigra and ventral tegmental area in the midbrain. These neurons project into the striatum, where dopamine axons bifurcate repeatedly and form dense axon networks (the striatum is separated into the caudate nucleus and putamen by the internal capsule). Midbrain dopamine neurons also innervate many other areas of the brain, including the cerebral cortex. Therefore, there are preclinical and clinical studies investigating extrastriatal dopamine mechanisms in motor control and Parkinson's disease pathophysiology and treatment. While extrastriatal dopamine can contribute, this contribution needs to be compared with the contribution of the striatal dopamine system. An isolated view of the extrastriatal dopamine system is like examining only the ear of an elephant and may lead to distorted assessments for preclinical and clinical research and diagnostic work. Thus, photographs of the whole brain dopamine system are important. For these reasons, we photographed the dopamine systems in whole mouse brain sagittal sections, showing clearly that, under identical imaging conditions, dopamine innervation is highly concentrated and intense in the striatum but sparse and weak in the cerebral cortex.
临床病理研究以及多巴胺能替代疗法的有效性证实，多巴胺缺失是帕金森病中导致运动症状的关键病理因素。帕金森病中受损的多巴胺神经元位于中脑的黑质和腹侧被盖区。这些神经元投射到纹状体，在那里多巴胺轴突反复分支并形成密集的轴突网络（纹状体被内囊分隔为尾状核和壳核）。中脑多巴胺神经元还支配大脑的许多其他区域，包括大脑皮层。因此，有临床前和临床研究在探究纹状体以外的多巴胺机制在运动控制、帕金森病病理生理学及治疗中的作用。虽然纹状体以外的多巴胺可能起作用，但需要将这种作用与纹状体多巴胺系统的作用进行比较。对纹状体以外的多巴胺系统进行孤立的研究，就如同只观察大象的耳朵，可能会导致对临床前和临床研究以及诊断工作的评估出现偏差。因此，全脑多巴胺系统的图像很重要。出于这些原因，我们拍摄了全脑矢状切片中的多巴胺系统，清楚地显示出，在相同的成像条件下，多巴胺神经支配在纹状体中高度集中且强烈，但在大脑皮层中稀疏且微弱。
