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Analysis of methamphetamine-induced neurotoxicity in the striatum of autopsied brains

尸检大脑纹状体中甲基苯丙胺诱导的神经毒性分析

基本信息

批准号：
17590579
负责人：
KITAMURA Osamu
金额：
$ 2.3万
依托单位：
The University of Tokushima
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

We demonstrated that decreases in tyrosine hydroxylase immunoreactivity in the nucleus accumbens and dopamine transporter in the nucleus accumbens and putamen were induced in methamphetamine (METH) users, whereas a significant difference of vesicular monoamine transporter-2 (VMAT2) was not evident between METH and control groups. However, in the nucleus accumbens of two METH users, levels of VMAT2, a stable marker of striatal dopaminergic terminal integrity, were reduced remarkably. These findings might indicate that dopaminergic terminal degeneration is induced in the striatum of some METH abusers. On the other hand, we observed little caspase・3 activation, indicative of apoptosis, in the striatal neurons of METH abusers. Overall, the findings of dopaminergic terminal markers were similar to those in the previous human study. Therefore, it is suggested that immunohistochemical techniques could be used to examine dopaminergic terminal marker levels and could also give useful informatio … More n on chronic and/or lethal METH use in cases of METH-related death, where METH intoxication may not be toxicologically demonstrated.We found significant increases in human glucose transporter-5-positive cells in chronic METH users; however, no proliferation of MHC class II-positive cells was found. GFAP-positive astrocytes increased, but not significantly, and vimentin expression was rarely observed. This study demonstrated a lack of microgliosis and astrogliosis in the striatum of chronic methamphetamine users. However, our observation of moderate glial reactions in human abusers is indicative of chronic METH abuse and suggests previously unrecognized roles of glial cells in the pathophysiology of METH abuse. Therefore, it is suggested that the immunohistochemical detection of glial reactions, together with the detection of decreases in dopaminergic terminal marker levels, would give useful information on METH abuse in cases of METH-related death.Further studies on brain-derived neurotrophic factor immunoreactivity and mitochondrial DNA deletion in the striatum of METH users are in progress. Less

我们证明，酪氨酸羟化酶的免疫反应性的减少，在神经核和多巴胺转运体的神经核和壳核诱导甲基苯丙胺（METH）用户，而囊泡单胺转运蛋白-2（VMAT 2）的显着差异是不明显的METH和对照组之间。然而，在两个METH用户的脑桥核中，纹状体多巴胺能末梢完整性的稳定标志物VMAT 2的水平显著降低。这些发现可能表明，多巴胺能末梢变性诱导纹状体的一些甲基滥用。另一方面，我们在METH滥用者的纹状体神经元中观察到很少的caspase·3活化，这表明细胞凋亡。总体而言，多巴胺能终末标志物的发现与先前的人体研究相似。因此，免疫组化技术可用于检测多巴胺能终末标记物水平，并可提供有用的信息， ...更多信息在METH相关死亡的病例中，METH中毒可能没有毒理学证明。我们发现慢性METH使用者中人葡萄糖转运蛋白-5阳性细胞显著增加;然而，没有发现MHC II类阳性细胞的增殖。GFAP阳性星形胶质细胞增加，但不显著，波形蛋白表达很少观察到。这项研究表明，缺乏小胶质细胞增生和星形胶质细胞增生的纹状体慢性甲基苯丙胺用户。然而，我们在人类滥用者中观察到的中度神经胶质反应表明慢性METH滥用，并表明神经胶质细胞在METH滥用的病理生理学中以前未被认识到的作用。因此，它是建议，免疫组化检测胶质反应，连同检测多巴胺能末梢标记物水平的下降，将提供有用的信息METH滥用的情况下METH-相关death.Further研究脑源性神经营养因子免疫反应性和线粒体DNA缺失在纹状体的METH用户正在进行中。少