Immunohistochemical investigation of dopaminergic terminal markers and caspase-3 activation in the striatum of human methamphetamine users
Immunohistochemical investigation of dopaminergic terminal markers and caspase-3 activation in the striatum of human methamphetamine users
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DOI：
10.1007/s00414-006-0087-9
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发表时间：
2007-05-01
影响因子：
2.1
通讯作者：
Kubo, Shin-ichi
中科院分区：
文献类型：
--
作者：
Kitamura, Osamu;Tokunaga, Itsuo;Kubo, Shin-ichi
甲基苯丙胺（冰毒）已被证明具有诱导作用。神经毒性。在先前的一项使用定量Western blotting和放射配体结合测定的人类研究中，慢性冰毒使用者诱导了多巴胺能末端标记物缺陷。在这项研究中，我们检验了免疫组织化学检测酪氨酸羟化酶（TH）、多巴胺转运蛋白（DAT）和囊泡单胺转运蛋白-2 （VMAT2）水平以及纹状体caspase-3激活对诊断冰毒滥用的适用性。甲基安非他明服毒者伏隔核TH免疫反应性降低，伏隔核和壳核DAT降低，而VMAT2在甲基安非他明与对照组之间差异不明显。然而，在两名冰毒使用者的伏隔核中，纹状体多巴胺能末端完整性的稳定标志VMAT2的水平显著降低。这些发现可能表明，在一些冰毒滥用者的纹状体中，多巴胺能终末变性是诱导的。另一方面，我们在慢性冰毒使用者的纹状体神经元中观察到很少的caspase-3激活，这表明细胞凋亡。总的来说，多巴胺能末端标记的发现与先前的人类研究相似。因此，建议免疫组织化学技术可用于检查多巴胺能末端标记水平，并可在甲基苯丙胺相关死亡病例中提供关于慢性和/或致命甲基苯丙胺使用的有用信息，甲基苯丙胺中毒可能没有毒理学证明。
Methamphetamine (METH) has been shown to induce. neurotoxicity. In a previous human study using quantitative Western blotting and radioligand binding assay, dopaminergic terminal marker deficits were induced in chronic METH users. In this study, we examined the suitability of the immunohistochemical detection of tyrosine hydroxylase (TH), dopamine transporter (DAT), and vesicular monoamine transporter-2 (VMAT2) levels, and caspase-3 activation in the striatum to diagnose METH abuse. Decreases in TH immunoreactivity in the nucleus accumbens and DAT in the nucleus accumbens and putamen were induced in METH users, whereas a significant difference of 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 chronic METH users. 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 information on chronic and/or lethal METH use in cases of METH-related death, where METH intoxication may not be toxicologically demonstrated.