Methamphetamine causes microglial activation in the brains of human abusers
Methamphetamine causes microglial activation in the brains of human abusers
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DOI：
10.1523/jneurosci.1179-08.2008
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发表时间：
2008-05-28
影响因子：
5.3
通讯作者：
Cadet, Jean L.
中科院分区：
文献类型：
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作者：
Sekine, Yoshimoto;Ouchi, Yasuomi;Cadet, Jean L.
甲基苯丙胺是一种流行的成瘾性药物，其使用与多种神经精神不良事件相关，并对大脑的多巴胺能和多巴胺能系统有毒。甲基苯丙胺诱导的神经病理学与小胶质细胞的表达增加有关，小胶质细胞被认为参与大脑中的促毒性或保护机制。虽然在甲基苯丙胺神经毒性的动物模型中观察到反应性小胶质细胞增生，但没有研究报告人类甲基苯丙胺滥用者中小胶质细胞活化的状态。本研究报告了12名戒断甲基苯丙胺滥用者和12名年龄、性别和教育程度匹配的对照受试者，他们接受了使用放射性示踪剂[C-11]（R）-（1-[ 2-氯苯基]-N-甲基-N-[ 1-甲基丙基]-3-异喹啉甲酰胺）（[C-11]（R）-PK 11195）进行的正电子发射断层扫描，以检测活化的小胶质细胞。使用Combustion分析来估计具有多巴胺能和/或多巴胺能神经支配的脑区域中[C-11]（R）-PK 11195的结合电位的定量水平。甲基苯丙胺滥用者的[C-11]（R）-PK 11195结合的平均水平在所有脑区都高于对照受试者（高出250%;所有p < 0.01）。此外，中脑、纹状体、丘脑、眶额皮质和岛叶皮质的结合水平（p < 0.05）与甲基苯丙胺戒断的持续时间呈负相关。这些结果表明，长期自我管理的甲基苯丙胺可以导致反应性小胶质细胞在人类甲基苯丙胺滥用者的大脑中，激活水平，似乎消退在较长时间的禁欲。
Methamphetamine is a popular addictive drug whose use is associated with multiple neuropsychiatric adverse events and toxic to the dopaminergic and serotonergic systems of the brain. Methamphetamine-induced neuropathology is associated with increased expression of microglial cells that are thought to participate in either pro-toxic or protective mechanisms in the brain. Although reactive microgliosis has been observed in animal models of methamphetamine neurotoxicity, no study has reported on the status of microglial activation in human methamphetamine abusers. The present study reports on 12 abstinent methamphetamine abusers and 12 age-, gender-, and education-matched control subjects who underwent positron emission tomography using a radiotracer for activated microglia, [C-11](R)-(1-[ 2-chlorophenyl]-N-methyl-N-[ 1-methylpropyl]-3-isoquinoline carboxamide) ([C-11](R)-PK11195). Compartment analysis was used to estimate quantitative levels of binding potentials of [C-11](R)-PK11195 in brain regions with dopaminergic and/ or serotonergic innervation. The mean levels of [C-11](R)-PK11195 binding were higher in methamphetamine abusers than those in control subjects in all brain regions (> 250% higher; p < 0.01 for all). In addition, the binding levels in the midbrain, striatum, thalamus, and orbitofrontal and insular cortices (p < 0.05) correlated inversely with the duration of methamphetamine abstinence. These results suggest that chronic self-administration of methamphetamine can cause reactive microgliosis in the brains of human methamphetamine abusers, a level of activation that appears to subside over longer periods of abstinence.