Developmental exposure to the organochlorine insecticide endosulfan damages the nigrostriatal dopamine system in male offspring.
Developmental exposure to the organochlorine insecticide endosulfan damages the nigrostriatal dopamine system in male offspring.
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DOI：
10.1016/j.neuro.2014.07.008
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发表时间：
2014-09
期刊：
影响因子：
3.4
通讯作者：
Caudle, W. Michael
中科院分区：
文献类型：
--
作者：
Wilson, W. Wyatt;Shapiro, Lauren P.;Bradner, Joshua M.;Caudle, W. Michael
环境毒物对帕金森病(PD)的病因和风险的贡献已经明确，有机氯杀虫剂通常被证明破坏黑质纹状体多巴胺途径。虽然帕金森病通常被认为是一种成人发病的疾病，但人们推测，在神经发育的关键时期，在生命的早期暴露于环境污染物或其他因素可能会改变多巴胺能回路，使个人更容易发生帕金森病。最近的流行病学证据发现，接触有机氯杀虫剂硫丹是帕金森病的危险因素。然而，与硫丹暴露相关的特定的多巴胺能靶点或脆弱的发育时间点尚未被研究。因此，我们试图调查发育过程中暴露于硫丹以及MPTP的额外挑战后的多巴胺能神经毒性。我们的体外研究结果表明，硫丹处理后SK-N-SH细胞和腹侧中脑原代培养细胞减少。在体内发育模型中，在怀孕和哺乳期接触硫丹会导致雄性后代纹状体中DAT和TH的减少。这些改变在随后的MPTP治疗后加剧。相比之下，成年小鼠暴露在硫丹中并没有引起多巴胺能损伤，也没有增加多巴胺神经元对MPTP的易感性。这些发现表明，妊娠期和哺乳期的发育是硫丹暴露和黑质纹状体多巴胺系统发育的关键窗口。此外，这些暴露似乎会使多巴胺神经元对晚年可能发生的额外侮辱敏感。
The contribution of environmental toxicants to the etiology and risk of Parkinson’s disease (PD) has been clearly established, with organochlorine insecticides routinely shown to damage the nigrostriatal dopamine pathway. Although PD is generally considered an adult onset disease, it has been postulated that exposure to environmental contaminants or other factors early in life during critical periods of neurodevelopment could alter the dopaminergic circuit and predispose individuals to developing PD. Recent epidemiological evidence has found exposure to the organochlorine insecticide endosulfan to be a risk factor for PD. However, the specific dopaminergic targets or vulnerable developmental time points related to endosulfan exposure have not been investigated. Thus, we sought to investigate dopaminergic neurotoxicity following developmental exposure to endosulfan as well as following an additional challenge with MPTP. Our in vitro findings demonstrate a reduction in SK-N-SH cells and ventral mesencephalic primary cultures after endosulfan treatment. Using an in vivo developmental model, exposure to endosulfan during gestation and lactation caused a reduction in DAT and TH in the striatum of male offspring. These alterations were exacerbated following subsequent treatment with MPTP. In contrast, exposure of adult mice to endosulfan did not elicit dopaminergic damage and did not appear to increase the vulnerability of the dopamine neurons to MPTP. These findings suggest that development during gestation and lactation represents a critical window of susceptibility to endosulfan exposure and development of the nigrostriatal dopamine system. Furthermore, these exposures appear to sensitize the dopamine neurons to additional insults that may occur later in life.
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DOI：
10.1080/009841000156907
发表时间：
2000-02-25
期刊：
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A
影响因子：
--
作者：
Corrigan, FM;Wienburg, CL;Mann, D
通讯作者：
Mann, D
影响因子：
9.8
作者：
Jimenez Torres, M.;Campoy Folgoso, C.;Olea-Serrano, F.
通讯作者：
Olea-Serrano, F.
影响因子：
3.4
作者：
Kitazawa, M;Anantharam, V;Kanthasamy, AG
通讯作者：
Kanthasamy, AG
影响因子：
4.4
作者：
MARTYN, CN;OSMOND, C
通讯作者：
OSMOND, C
影响因子：
3.5
作者：
Ratra, GS;Casida, JE
通讯作者：
Casida, JE