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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >The role of iron and copper molecules in the neuronal vulnerability of locus coeruleus and substantia nigra during aging.
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The role of iron and copper molecules in the neuronal vulnerability of locus coeruleus and substantia nigra during aging.

机译：铁和铜分子在衰老过程中蓝斑和黑质神经元脆弱性中的作用。

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In this study, a comparative analysis of metal-related neuronal vulnerability was performed in two brainstem nuclei, the locus coeruleus (LC) and substantia nigra (SN), known targets of the etiological noxae in Parkinson's disease and related disorders. LC and SN pars compacta neurons both degenerate in Parkinson's disease and other Parkinsonisms; however, LC neurons are comparatively less affected and with a variable degree of involvement. In this study, iron, copper, and their major molecular forms like ferritins, ceruloplasmin, neuromelanin (NM), manganese-superoxide dismutase (SOD), and copper/zinc-SOD were measured in LC and SN of normal subjects at different ages. Iron content in LC was much lower than that in SN, and the ratio heavy-chain ferritin/iron in LC was higher than in the SN. The NM concentration was similar in LC and SN, but the iron content in NM of LC was much lower than SN. In both regions, heavy- and light-chain ferritins were present only in glia and were not detectable in neurons. These data suggest that in LC neurons, the iron mobilization and toxicity is lower than that in SN and is efficiently buffered by NM. The bigger damage occurring in SN could be related to the higher content of iron. Ferritins accomplish the same function of buffering iron in glial cells. Ceruloplasmin levels were similar in LC and SN, but copper was higher in LC. However, the copper content in NM of LC was higher than that of SN, indicating a higher copper mobilization in LC neurons. Manganese-SOD and copper/zinc-SOD had similar age trend in LC and SN. These results may explain at least one of the reasons underlying lower vulnerability of LC compared to SN in Parkinsonian syndromes.
机译：在这项研究中，对与金属相关的神经元易损性进行了比较分析，这两个脑干核是蓝斑（LC）和黑质（SN），这是帕金森氏病和相关疾病的病原学已知靶标。 LC和SN解析致密性神经元均在帕金森氏病和其他帕金森病中退化。但是，LC神经元受到的影响相对较小，并且受累程度不同。在这项研究中，在正常年龄的正常人的LC和SN中测量了铁，铜及其主要分子形式，如铁蛋白，铜蓝蛋白，神经黑色素（NM），锰超氧化物歧化酶（SOD）和铜/锌SOD。 LC中的铁含量远低于SN，LC中的重链铁蛋白/铁比高于SN。 LC和SN中的NM浓度相似，但LC NM中的铁含量远低于SN。在这两个区域中，重链和轻链铁蛋白仅存在于神经胶质中，而在神经元中则无法检测到。这些数据表明，在LC神经元中，铁的动员和毒性低于SN，并且被NM有效地缓冲。 SN中发生的较大破坏可能与铁含量较高有关。铁蛋白具有在胶质细胞中缓冲铁的相同功能。 LC和SN中的铜蓝蛋白水平相似，但LC中的铜较高。然而，LC NM中的铜含量高于SN，表明LC神经元中的铜迁移率更高。 LC和SN中锰SOD和铜/锌SOD的年龄趋势相似。这些结果至少可以解释帕金森氏综合征中LC较SN更低的脆弱性的原因之一。

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