Selective effects of insecticides on nigrostriatal dopaminergic nerve pathways
Selective effects of insecticides on nigrostriatal dopaminergic nerve pathways
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DOI：
10.1016/s0161-813x(02)00031-1
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发表时间：
2002-10-01
期刊：
影响因子：
3.4
通讯作者：
Kirby, ML
中科院分区：
文献类型：
--
作者：
Bloomquist, JR;Barlow, RL;Kirby, ML
黑质纹状体通路的退化是帕金森氏病(PD)的主要组成部分，我们研究了杀虫剂在这一通路上的作用。对于活体暴露，C57BL/6小鼠在两周内接受了七氯、拟除虫菊酯、溴氰菊酯和二氯菊酯或毒死蜱三次治疗。在最后一次治疗后的一天，我们观察到七氯和拟除虫菊酯增加了处理小鼠纹状体突触体的最大[H-3]多巴胺摄取，V-max随剂量的变化呈钟形曲线。Western印迹分析证实，七氯菊酯和氯氰菊酯处理的小鼠纹状体内多巴胺转运体(DAT)蛋白水平增加。相反，我们观察到100毫克/公斤毒死蜱的多巴胺摄取量略有下降，但在统计学上有显著意义。对于七氯，上调DAT表达的剂量对5-羟色胺的转运几乎没有影响。氯菊酯确实引起了5-羟色胺转运的上调，但所需剂量是对多巴胺摄取有效剂量的30倍。在递质释放试验中也发现了其他特异性的证据，其中七氯和溴氰菊酯从纹状体终末释放多巴胺的效力比其他类型的递质更大。这些发现证实了杀虫剂对纹状体多巴胺能神经传递的影响具有特异性。(C)2002 Elsevier Science Inc.保留所有权利。
A degeneration of the nigrostriatal pathway is a primary component of Parkinson's disease (PD), and we have investigated the actions of insecticides on this pathway. For in vivo exposures, C57BL/6 mice were treated three times over a 2-week period with heptachlor the pyrethroids deltamethrin and permethrin, or chlorpyrifos. One day after the last treatment, we observed that heptachlor and the pyrethroids increased maximal [H-3]dopamine uptake in striatal synaptosomes from treated mice, with dose-dependent changes in V-max displaying a bell-shaped curve. Western blot analysis confirmed increased levels of dopamine transporter (DAT) protein in the striatum of mice treated with heptachlor and permethrin. In contrast, we observed a small, but statistically significant decrease in dopamine uptake by 100 mg/kg chlorpyrifos. For heptachlor doses that upregulated DAT expression had little or no effect on serotonin transport. Permethrin did cause an upregulation of serotonin transport, but required a 30-fold greater dose than that effective on dopamine uptake. Other evidence of specificity was found in transmitter release assays, where heptachlor and deltamethrin released dopamine from striatal terminals with greater potency than other transmitter types. These findings confirm that insecticides possess specificity for effects on striatal dopaminergic neurotransmission. (C) 2002 Elsevier Science Inc. All rights reserved.