Ben-Shachar D, Youdim M B
Department of Pharmacology, Bruce Rappaport Faculty of Medicine, Haifa, Israel.
J Neurochem. 1991 Dec;57(6):2133-5. doi: 10.1111/j.1471-4159.1991.tb06432.x.
Elevated iron concentrations in the substantia nigra (SN) pars compacta have been implicated in the development of idiopathic Parkinson's disease. Because, as a transitional metal, iron promotes free radical formation, the role of iron in the degeneration of the nigrostriatal dopamine neurons in Parkinson's disease has received much attention. This study further investigates the cytotoxic effects of iron in the SN. Various concentrations of FeCl3 (1, 5, and 50 micrograms of Fe3+ in 5 microliters) were unilaterally injected into the SN of adult rats. The two lower doses of iron had no effect on striatal dopamine levels or on the behavioral responses of the rats. However, injection of 50 micrograms of Fe3+ resulted in a substantial selective decrease of striatal dopamine (95%), 3,4-dihydroxyphenylacetic acid (82%), and homovanillic acid (45%), without any change in norepinephrine concentration. Dopamine-related behavioral responses, such as spontaneous movements in a novel space and rearing, were significantly impaired, whereas amphetamine administration induced ipsilateral rotation in the iron-treated rats. The present study indicates that the nigrostriatal dopamine neurons are susceptible to the presence of ionic iron and thus supports the assumption that iron initiates dopaminergic neurodegeneration in Parkinson's disease.
黑质致密部铁浓度升高与特发性帕金森病的发生有关。由于铁作为一种过渡金属会促进自由基的形成，因此铁在帕金森病黑质纹状体多巴胺能神经元变性中的作用备受关注。本研究进一步探讨铁在黑质中的细胞毒性作用。将不同浓度的FeCl3（5微升中含1、5和50微克Fe3+）单侧注射到成年大鼠的黑质中。较低剂量的两种铁对纹状体多巴胺水平或大鼠的行为反应没有影响。然而，注射50微克Fe3+导致纹状体多巴胺（95%）、3,4-二羟基苯乙酸（82%）和高香草酸（45%）显著选择性降低，而去甲肾上腺素浓度没有任何变化。多巴胺相关的行为反应，如在新环境中的自发运动和竖毛，明显受损，而给予苯丙胺会使经铁处理的大鼠向同侧旋转。本研究表明黑质纹状体多巴胺能神经元对离子铁的存在敏感，因此支持铁引发帕金森病中多巴胺能神经变性的假设。
