Occurrence of neuronal inclusions combined with increased nigral expression of α-synuclein within dopaminergic neurons following treatment with amphetamine derivatives in mice
Occurrence of neuronal inclusions combined with increased nigral expression of α-synuclein within dopaminergic neurons following treatment with amphetamine derivatives in mice
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DOI：
10.1016/j.brainresbull.2005.02.022
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发表时间：
2005-05-15
影响因子：
3.8
通讯作者：
Paparelli, A
中科院分区：
文献类型：
--
作者：
Fornai, F;Lenzi, P;Paparelli, A
近年来，一些临床和研究结果表明，突触前蛋白α-突触核蛋白与多种神经退行性疾病（称为突触核蛋白病）有关。尽管这种蛋白质在细胞生理学中的功能仍然未知，但很明显，遗传改变或单纯天然分子的过度表达都会导致含有黑质多巴胺的神经元变性，从而导致运动障碍，正如遗传性帕金森病所证明的那样。在本研究中，我们研究了广泛滥用的药物，如甲基苯丙胺和亚甲二氧基甲基苯丙胺（摇头丸），已知会损害小鼠黑质纹状体多巴胺通路，是否会增加黑质致密部多巴胺神经元内α-突触核蛋白的表达。本研究的结果表明，安非他明衍生物产生的黑质纹状体多巴胺去神经和黑质神经元细胞内包涵体的发生与黑质多巴胺神经元内α-突触核蛋白表达的增加有关。这为以下假设提供了依据：天然 α-syrrclein 数量的增加本身可能是多巴胺神经元的有害因素。 (c) 2005 Elsevier Inc. 保留所有权利。
In recent years several clinical and research findings have demonstrated the involvement of the presynaptic protein alpha-synuclein in a variety of neurodegenerative disorders which are known as synucleinopathies. Although the function of this protein in the physiology of the cell remains unknown, it is evident that both genetic alterations or a mere overexpression of the native molecule produces a degeneration of nigral dopamine-containing neurons leading to movement disorders, as demonstrated in inherited Parkinson's disease. In the present study, we investigated whether widely abused drugs such as methamphetamine and methylenedioxymethamphetamine (ecstasy), which are known to damage the nigrostriatal dopamine pathway of mice, increase the expression of alpha-synuclein within dopamine neurons of the substantia nigra pars compacta. The results of this study demonstrate that nigrostriatal dopamine denervation and occurrence of intracellular inclusions in nigral neurons produced by amphetamine derivatives are related to increased expression of alpha-synuclein within dopamine neurons of the substantia nigra. This lends substance to the hypothesis that increased amounts of native alpha-syrruclein may be per se a detrimental factor for the dopamine neurons. (c) 2005 Elsevier Inc. All rights reserved.