Iron in the basal ganglia in Parkinson's disease -: An in vitro study using extended X-ray absorption fine structure and cryo-electron microscopy
Iron in the basal ganglia in Parkinson's disease -: An in vitro study using extended X-ray absorption fine structure and cryo-electron microscopy
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DOI：
10.1093/brain/122.4.667
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发表时间：
1999-04-01
期刊：
影响因子：
14.5
通讯作者：
Clarke, DT
中科院分区：
文献类型：
--
作者：
Griffiths, PD;Dobson, BR;Clarke, DT
铁在大脑的某些区域含量很高，黑质中铁的增加是帕金森病的一个特征。本研究的目的是调查死后组织中脑铁的物理环境，以提供有关铁在帕金森病神经变性中可能发挥的作用的信息。铁也被认为是 T-2 加权 MRI 序列中脑铁含量高的区域信号丢失的原因。了解脑铁的物理环境对于解释信号变化的原因至关重要，从六例帕金森病患者和六名年龄匹配的对照中获得死后组织，使用吸收分光光度法测量铁水平，使用扩展X射线吸收精细结构来评估黑质和苍白球两段内铁的原子环境，使用冷冻电子透射显微镜探测这些区域中的铁储存蛋白。帕金森病黑质和苍白球外侧部分的铁水平增加，扩展 X 射线吸收精细结构实验的光谱表明，铁蛋白是所有研究区域的对照组织和帕金森病组织中唯一可检测到的储存蛋白。冷冻电子透射显微镜研究表明，与年龄匹配的对照组相比，帕金森病患者的铁蛋白铁含量更高。总之，我们已经表明，帕金森病患者大脑的两个区域中的铁水平增加，包括黑质（神经退行性最严重的部位），这会增加铁蛋白的负荷，铁蛋白是正常的大脑铁储存蛋白。铁蛋白负荷的增加可能会增加自由基引起的损伤的风险。铁蛋白含量的差异可以解释铁对 T-2 信号影响的区域差异。
Iron is found in high concentration in some areas of the brain, and increased iron in the substantia nigra isa feature of Parkinson's disease. The purpose of this study was to investigate the physical environment of brain iron in post-mortem tissue to provide information on the possible role of iron in neurodegeneration in Parkinson's disease. Iron has also been implicated as the cause of signal loss in areas of high brain iron on T-2-weighted MRI sequences. Knowledge of the physical environment of the brain iron is essential in interpreting the cause of signal change, Post-mortem tissue was obtained from six cases of Parkinson's disease and from six age-matched controls, Iron levels were measured using absorption spectrophotometry, Extended X-ray absorption fine structure was used to evaluate the atomic environment of iron within the substantia nigra and both segments of the globus pallidus, Cryo-electron transmission microscopy was used to probe the iron storage proteins in these areas. Iron levels were increased in the parkinsonian nigra and lateral portion of the globus pallidus, Spectra from the extended X-ray absorption fine structure experiments showed that ferritin was the only storage protein detectable in both control and parkinsonian tissue in all areas studied. Cryo-electron transmission microscopy studies showed that ferritin was more heavily loaded with iron in Parkinson's disease when compared with age-matched controls. In summary we have shown that iron levels are increased in two areas of the brain in Parkinson's disease including the substantia nigra, the site of maximal neurodegeneration, This produces increased loading of ferritin, which is the normal brain iron storage protein. It is possible that increased loading of ferritin may increase the risk of free radical-induced damage. Differences in ferritin loading may explain regional differences in iron's effect on the T-2 signal.