Department of Neurobiology and Therapeutics, Graduate School and Faculty of Pharmaceutical Sciences, The University of Tokushima, 1-78, Sho-machi, Tokushima, 770-8505, Japan.
J Mol Neurosci. 2010 May;41(1):17-24. doi: 10.1007/s12031-009-9220-9. Epub 2009 Jul 31.
Systematic administration of rotenone as one of pesticides is known to produce degeneration of nigral dopaminergic neurons and motor deficits in experimental animals. Here, we investigated to determine whether systematic administration of rotenone causes the increased susceptibility in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. Rotenone was injected into MPTP-treated mice over a period of 4 weeks. Thereafter, we evaluated the effect of rotenone 1, 3, and 6 weeks after the cessation of treatment with rotenone. In the present study with HPLC analysis, rotenone did not enhance MPTP-induced dopaminergic neurotoxicity in mice. Furthermore, MPTP + rotenone (9 mg/kg)-treated mice exhibit a significant loss of motor activity 1 day after the cessation of treatment with rotenone, However, no significant change of motor activity was found in MPTP-treated and MPTP + rotenone (9 mg/kg)-treated animals 6 weeks after the cessation of treatment with 0.5% carboxymethyl cellulose or rotenone. Our Western blot analysis study demonstrated that the change of tyrosine hydroxylase and glial fibrillary acidic protein protein levels in MPTP-treated mice was similar than that in MPTP + rotenone-treated animals. These results suggest that rotenone did not enhance MPTP neurotoxicity in mice. Our findings suggest that rotenone is not a reliable model for PD. Thus, our findings provide further valuable information for the pathogenesis of PD for exposure to agricultural pesticides.
鱼藤酮作为一种杀虫剂，系统给药会导致实验动物黑质多巴胺能神经元退化和运动功能障碍。在这里，我们研究了鱼藤酮是否会增加 MPTP 处理的小鼠对其的易感性。鱼藤酮在 4 周的时间内被注射到 MPTP 处理的小鼠体内。此后，我们在停止鱼藤酮治疗后 1、3 和 6 周评估了鱼藤酮的作用。在本研究中，通过 HPLC 分析，鱼藤酮并没有增强 MPTP 诱导的小鼠多巴胺能神经毒性。此外，在停止鱼藤酮治疗 1 天后，MPTP+鱼藤酮（9mg/kg）处理的小鼠表现出明显的运动活性丧失，但在停止 0.5%羧甲基纤维素或鱼藤酮治疗 6 周后，MPTP 处理和 MPTP+鱼藤酮（9mg/kg）处理的动物的运动活性没有明显变化。我们的 Western blot 分析研究表明，MPTP 处理小鼠中酪氨酸羟化酶和胶质纤维酸性蛋白蛋白水平的变化与 MPTP+鱼藤酮处理动物相似。这些结果表明，鱼藤酮并没有增强 MPTP 在小鼠中的神经毒性。我们的发现表明，鱼藤酮不是 PD 的可靠模型。因此，我们的发现为接触农业杀虫剂导致的 PD 发病机制提供了进一步有价值的信息。
