Detection of methamphetamine neurotoxicity in forensic autopsy cases.
Detection of methamphetamine neurotoxicity in forensic autopsy cases.
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DOI：
10.1016/j.legalmed.2009.01.003
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发表时间：
2009-04-01
期刊：
影响因子：
--
通讯作者：
Kitamura, Osamu
中科院分区：
文献类型：
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作者：
Kitamura, Osamu
甲基苯丙胺（Methamphetamine，简称冰毒）是一种强效兴奋剂，滥用后具有强烈的成瘾性和神经毒性。甲基苯丙胺神经毒性的特点是纹状体单胺的长期耗竭。甲基苯丙胺诱导的多巴胺释放产生活性氢，被认为在甲基苯丙胺神经毒性中起重要作用。应用免疫组织化学技术检测了甲基苯丙胺滥用者纹状体中酪氨酸羟化酶（TH）、多巴胺转运蛋白（DAT）和水泡单胺转运蛋白2 （VMAT2）水平和神经胶质反应。甲基苯丙胺使用者TH免疫反应性和DAT水平明显下降。尽管VMAT2水平的显著差异并不常见，但VMAT2水平（纹状体多巴胺能末端完整性的稳定标志）在一些冰毒使用者中显著降低。此外，纹状体中小胶质细胞的数量显著增加，尽管胶质细胞的激活并不明显。此外，我们还评估了冰毒滥用者大脑中72-kDa热休克蛋白（HSP72）的表达。海马和其他区域观察到HSP72免疫反应性。尽管热休克蛋白可能是由甲基苯丙胺的其他作用引起的，但这些发现可能表明甲基苯丙胺诱导的神经毒性导致了高温。免疫组织化学检测多巴胺能末端标记物缺陷、神经胶质反应和热休克蛋白诱导，可能会在甲基苯丙胺相关死亡病例中，为慢性和/或致命性甲基苯丙胺使用的病理生理学提供有用的信息，甲基苯丙胺中毒可能没有毒理学证明。
Methamphetamine (METH) is a powerful stimulant drug of abuse with potent addictive and neurotoxic properties. METH neurotoxicity is characterized by the long-term depletion of striatal monoamines. METH-induced release of dopamine generates reactive hydrogen species, which are proposed to play an important role in METH neurotoxicity. The tyrosine hydroxylase (TH), dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT2) levels and glial reactions in the striata of METH abusers were examined using immunohistochemical technique. Decreases in TH immunoreactivity and DAT levels were evident in METH users. Although significant differences in VMAT2 levels were not common, the levels of VMAT2--a stable marker of striatal dopaminergic terminal integrity--were remarkably reduced in some METH users. Further, significant increases were observed in the number of microglia in the striatum although the activation of glial cells was not evident. In addition, the expression of 72-kDa heat shock proteins (HSP72) in the brains of METH abusers was assessed. HSP72 immunoreactivity was observed in the hippocampus and other areas. These findings may be indicative of hyperthermia due to METH-induced neurotoxicity although it is possible that HSPs are induced by other effects of METH. Immunohistochemical detection of dopaminergic terminal marker deficits, glial reactions, and HSP induction might provide useful information regarding the pathophysiology of chronic and/or lethal METH use in cases of METH-related deaths, where METH intoxication may not be toxicologically demonstrated.