MPTP-Induced Dopamine Neuron Degeneration and Glia Activation Is Potentiated in MDMA-Pretreated Mice
MPTP-Induced Dopamine Neuron Degeneration and Glia Activation Is Potentiated in MDMA-Pretreated Mice
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DOI：
10.1002/mds.25646
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发表时间：
2013-12-01
影响因子：
8.6
通讯作者：
Morelli, Micaela
中科院分区：
文献类型：
--
作者：
Costa, Giulia;Frau, Lucia;Morelli, Micaela
临床观察报告苯丙胺使用者患帕金森氏病(PD)的倾向更大。3，4-亚甲基二氧基甲基苯丙胺(MDMA；摇头丸)是一种苯丙胺相关药物，主要由青少年和年轻人消费，可能具有神经炎症和神经毒性作用。在这里，目的是在小鼠身上评估青春期服用MDMA是否会影响1-甲基-4-苯基-1，2，3，6-四氢吡啶(MPTP)的神经炎症和神经毒性效应，MPTP是一种已知的导致人类帕金森病的毒素。用胶质纤维酸性蛋白(GFAP)和补体受体3型(CD11b)免疫组织化学方法检测星形胶质细胞和小胶质细胞的激活，用酪氨酸羟基酶(TH)免疫组织化学方法检测多巴胺能神经元的变性。MPTP(20 mg/kg×4)给8周龄~17周龄的小鼠灌胃MDMA(10 mg/kg，每天2次，每周2次)。在长期接受MDMA治疗的小鼠中，与赋形剂或赋形剂+MPTP治疗的小鼠相比，MPTP在纹状体和黑质致密部(SNC)诱导了更高的小胶质和星形胶质细胞反应。与赋形剂组、MDMA组和MPTP组小鼠相比，MDMA+MPTP组小鼠的SNC中TH免疫反应降低，纹状体和SNC中的SNC进一步减少。结果表明，在小鼠青春期晚期长期给予MDMA可加重MPTP引起的神经变性和神经炎症，提示MDMA可能是多巴胺能神经元变性的危险因素之一。(C)2013年国际帕金森病和运动障碍协会
Clinical observations report a greater propensity to develop Parkinson's disease (PD) in amphetamine users. 3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) is an amphetamine-related drug that is largely consumed by adolescents and young adults, which may have neuroinflammatory and neurotoxic effects. Here, the objective was to evaluate in mice whether consumption of MDMA during adolescence might influence the neuroinflammatory and neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a toxin known to induce PD in humans. The activation of astroglia and microglia by glial fibrillary acidic protein (GFAP) and complement receptor type 3 (CD11b) immunohistochemistry and the degeneration of dopaminergic neurons by tyrosine hydroxylase (TH) immunohistochemistry were evaluated. MPTP (20 mg/kg x 4) was administered to mice treated from ages 8 weeks to 17 weeks with MDMA (10 mg/kg twice daily, two times a week). In mice that were chronically treated with MDMA, administration of MPTP induced a higher microglial and astroglial response in both the striatum and the substantia nigra pars compacta (SNc) compared with vehicle-treated or vehicle+MPTP-treated mice. Inflammatory changes were associated with a decrease in TH immunoreactivity in the SNc of MDMA-treated mice and with a further decrease in the striatum and the SNc of MDMA+MPTP-treated mice compared with vehicle-treated, MDMA-treated, and MPTP-treated mice. The results demonstrate that chronic administration of MDMA during late adolescence in mice exacerbates the neurodegeneration and neuroinflammation caused by MPTP, suggesting that MDMA may constitute a risk factor for dopaminergic neuron degeneration. (c) 2013 International Parkinson and Movement Disorder Society