Zecca L, Swartz H M
Istituto Tecnologie Biomediche Avanzate, CNR, Milano, Italy.
J Neural Transm Park Dis Dement Sect. 1993;5(3):203-13. doi: 10.1007/BF02257675.
A number of hypotheses on the etiology of Parkinson's disease and other CNS disorders postulate a role of metal ions and/or neuromelanin. As part of an investigation of the interactions between neuromelanin and metal ions, we have studied the amount and type of metal ions in human neuromelanin in intact substantia nigra and in isolated neuromelanin using electron paramagnetic resonance (EPR), which selectively measures metal ions which are in valence states that have unpaired electrons and total reflection X-ray fluorescence (TXRF), which measures total metals. EPR also is a principal technique for studying the biophysics of melanins by analysis of its free radicals. The studies of substantia nigra with TXRF indicated the presence of substantial amounts of iron, zinc, lead, copper, manganese, and titanium at concentrations up to 4 times greater than those of non-pigmented brain tissue (basis pedunculi). The concentrations of metal ions in isolated neuromelanin were 5-260 times higher than in substantia nigra. The studies with EPR indicated that there were substantial amounts of paramagnetic metals ions, especially iron, bound to neuromelanin in intact substantia nigra, and the presence of these metal ions modified the EPR spectra of the free radicals of neuromelanin. We conclude: 1. Compared to other regions of the mid-brain, the substantia nigra contains increased amounts of many different metal ions; 2. Many of these metal ions are in paramagnetic valence states; 3. There are high concentrations of paramagnetic metal ions bound to neuromelanin. These results are consistent with the hypotheses that postulate a role of metal ions in promoting oxidative reactions in pigmented neurons.
关于帕金森病及其他中枢神经系统疾病的病因,有多种假说认为金属离子和/或神经黑素起了一定作用。作为对神经黑素与金属离子相互作用研究的一部分,我们使用电子顺磁共振(EPR)和全反射X射线荧光(TXRF)研究了完整黑质中人类神经黑素以及分离出的神经黑素中的金属离子含量和类型。EPR可选择性测量具有未成对电子价态的金属离子,TXRF则用于测量总金属含量。EPR也是通过分析黑色素自由基来研究其生物物理学的主要技术。用TXRF对黑质的研究表明,其铁、锌、铅、铜、锰和钛的含量相当可观,浓度比非色素脑组织(脑脚)高4倍。分离出的神经黑素中金属离子的浓度比黑质中的高5至260倍。EPR研究表明,完整黑质中与神经黑素结合的顺磁性金属离子含量很高,尤其是铁,这些金属离子的存在改变了神经黑素自由基的EPR光谱。我们得出以下结论:1. 与中脑的其他区域相比,黑质中多种不同金属离子的含量增加;2. 其中许多金属离子处于顺磁价态;3. 与神经黑素结合的顺磁性金属离子浓度很高。这些结果与认为金属离子在有色神经元中促进氧化反应起作用的假说一致。