Mancozeb-induced behavioral deficits precede structural neural degeneration
Mancozeb-induced behavioral deficits precede structural neural degeneration
复制标题
DOI：
10.1016/j.neuro.2012.10.007
复制
发表时间：
2013-01-01
期刊：
影响因子：
3.4
通讯作者：
Raley-Susman, Kathleen M.
中科院分区：
文献类型：
--
作者：
Brody, A. Harrison;Chou, Eunice;Raley-Susman, Kathleen M.
代森锰锌等含锰杀菌剂与帕金森氏症等神经退行性疾病有关。我们研究了代森锰锌暴露引起的行为损害和不同的神经元脆弱性，线虫是一种重要的中等营养级土壤有机体，也是研究环境污染物诱导的神经退行性疾病机制的有效模型。多巴胺介导的从游泳到爬行的运动转换行为非常容易受到代森锰锌的影响，其功能损害先于神经元结构损害的标志。在缺乏二价金属转运蛋白SMF-1的突变体中，这种损伤被部分挽救，这表明部分但不是所有的损伤是由锰介导的。代森锰锌浓度的增加会引起额外的行为障碍，特别是5-羟色胺介导的产卵行为，但没有明显的5-羟色胺能神经元结构损伤。因此，行为功能障碍的测量是杀菌剂毒性的一个敏感的早期标志，可以用来研究神经元损伤的进一步机制和可能的治疗干预措施。这些结果也为杀菌剂的使用对线虫生态行为的后果提供了重要的见解。(C)2012 Elsevier Inc.保留所有权利。
Manganese-containing fungicides like Mancozeb have been associated with neurodegenerative conditions like Parkinson's disease. We examined the behavioral damage and differential neuronal vulnerability resulting from Mancozeb exposure using Caenorhabditis elegans, an important mid-trophic level soil organism that is also a powerful model for studying mechanisms of environmental pollutant-induced neurodegenerative disease. The dopamine-mediated swim to crawl locomotory transition behavior is exquisitely vulnerable to Mancozeb, with functional impairment preceding markers of neuronal structural damage. The damage is partially rescued in mutants lacking the divalent metal transporter, SMF-1, demonstrating that some, but not all, of the damage is mediated by manganese. Increasing concentrations of Mancozeb recruit additional behavioral dysfunction, notably serotonin-mediated egg-laying behavior, but without evident serotonergic neuronal structural damage. Thus, measurements of behavioral dysfunction are a sensitive early marker of fungicide toxicity that could be exploited to examine further mechanisms of neuron damage and possible therapeutic interventions. These results also provide important insight into the consequences of fungicide use on the ecological behavior of nematodes. (c) 2012 Elsevier Inc. All rights reserved.