Division of Psychobiology, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan.
Curr Neuropharmacol. 2011 Mar;9(1):96-9. doi: 10.2174/157015911795016985.
MDMA (3,4-methylenedioxymethamphetamine) is reportedly severely toxic to both dopamine (DA) and serotonin neurons. MDMA significantly reduces the number of DA neurons in the substantia nigra, but not in the nucleus accumbens, indicating that MDMA causes selective destruction of DA neurons in the nigrostriatal pathway, sparing the mesolimbic pathway. Parkinson's disease (PD) is a neurodegenerative disorder of multifactorial origin. The pathological hallmark of PD is the degeneration of DA neurons in the nigrostriatal pathway. Mutations in the parkin gene are frequently observed in autosomal recessive parkinsonism in humans. Parkin is hypothesized to protect against neurotoxic insult, and we attempted to clarify the role of parkin in MDMA-induced hyperthermia, one of the causal factors of neuronal damage, using parkin knockout mice. Body temperature was measured rectally before and 15, 30, 45, and 60 min after intraperitoneal injection of MDMA (30 mg/kg) at an ambient temperature of 22 ± 2°C. Significantly enhanced hyper-thermia after MDMA injection was observed in heterozygous and homozygous parkin knockout mice compared with wildtype mice, suggesting that parkin plays a protective role in MDMA neurotoxicity.
3,4-亚甲二氧基甲基苯丙胺（MDMA）据报道对多巴胺（DA）和 5-羟色胺神经元都有严重毒性。MDMA 显著减少黑质中的 DA 神经元数量，但不减少伏隔核中的 DA 神经元，表明 MDMA 导致黑质纹状体通路中的 DA 神经元选择性破坏，而保留中脑边缘通路。帕金森病（PD）是一种多因素起源的神经退行性疾病。PD 的病理标志是黑质纹状体通路中的 DA 神经元退化。人类常染色体隐性遗传帕金森病中经常观察到 parkin 基因突变。Parkin 被假设为保护免受神经毒性损伤，我们试图使用 parkin 敲除小鼠阐明 parkin 在 MDMA 诱导的发热（神经元损伤的原因之一）中的作用，该发热在环境温度为 22±2°C 时，在腹腔注射 MDMA（30mg/kg）之前和之后 15、30、45 和 60 分钟通过直肠测量体温。与野生型小鼠相比，杂合和纯合 parkin 敲除小鼠在 MDMA 注射后表现出明显增强的发热，表明 parkin 在 MDMA 神经毒性中发挥保护作用。
