Hornykiewicz O
Wien Klin Wochenschr. 1985 Apr 12;97(8):350-4.
Neurochemical studies in Parkinson's disease have greatly contributed to the understanding of the neurobiology of the meso-telencephalic dopamine (DA) system; in addition, these studies have significantly influenced our concepts regarding the general principles of brain function. The primary role of DA in striatal function can be seen in its ability to initiate complex patterns of motor activity. The nigro-striatal DA system shows in the face of partial damage an extraordinarily high degree of plasticity, i.e. capacity for functional compensation. The two most important mechanisms of plasticity of the nigro-striatal DA system are: compensatory activation of the presynaptic remaining DA neurons (through increase in DA turnover); and increase in the number of postsynaptic DA receptors. The DA loss which occurs during normal ageing is not of sufficient magnitude to cause clinically overt Parkinson's disease. On the other hand, the observations pertaining to the Parkinsonian syndrome produced by NMPTP suggest the participation of environmental factors in the aetiology of idiopathic Parkinson's disease. The remarkable results of nigral cell transplants into the striatum of animals with experimental "parkinsonism", as well as the high therapeutic efficacy of DA substitution in patients with Parkinson's disease point toward a neurohumoral, rather than neurotransmitter, function of brain DA.
帕金森病的神经化学研究极大地促进了对中脑-边缘多巴胺(DA)系统神经生物学的理解;此外,这些研究还显著影响了我们对脑功能一般原理的概念。DA在纹状体功能中的主要作用可从其启动复杂运动活动模式的能力中看出。黑质-纹状体DA系统在面对部分损伤时表现出极高的可塑性,即功能补偿能力。黑质-纹状体DA系统可塑性的两个最重要机制是:突触前剩余DA神经元的代偿性激活(通过DA周转率增加);以及突触后DA受体数量增加。正常衰老过程中发生的DA丧失程度不足以导致临床上明显的帕金森病。另一方面,与NMPTP所致帕金森综合征相关的观察结果提示环境因素参与特发性帕金森病的病因。将黑质细胞移植到实验性“帕金森病”动物纹状体中的显著结果,以及DA替代疗法对帕金森病患者的高治疗效果,都表明脑DA具有神经体液而非神经递质的功能。