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幼龄雄性C57BL/6小鼠经口接触除草剂阿特拉津所致的多巴胺能毒性

Dopaminergic toxicity associated with oral exposure to the herbicide atrazine in juvenile male C57BL/6 mice.

作者信息

Coban A, Filipov N M

机构信息

Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi 39762-6100, USA.

出版信息

J Neurochem. 2007 Mar;100(5):1177-87. doi: 10.1111/j.1471-4159.2006.04294.x. Epub 2007 Jan 8.

DOI:10.1111/j.1471-4159.2006.04294.x
PMID:17217422
Abstract

The herbicide atrazine (ATR) is a very commonly used pesticide in the United States. and a major ground water contaminant. It has also been recently implicated as a potential basal ganglia toxicant. In the present study, our objective was to determine the effects of ATR exposure on striatal neurochemistry, on the number of dopaminergic neurons in the substantia nigra pars compacta (SNpc), and, as a reference, in the ventral tegmental area (VTA) of male juvenile C57BL/6 mice. Oral exposure to ATR for 14 days dose-dependently decreased the levels of dopamine (DA) and its metabolites in the striatum for up to a week post-treatment. ATR exposure also time- and dose-dependently decreased the number of tyrosine hydroxylase-positive (TH+) dopaminergic neurons in both SNpc and VTA (with effects being slightly more prominent in SNpc), such that the decreases were most evident at 7 weeks post-cessation of exposure to ATR. Together, these data indicate that, in the juvenile male C57BL/6 mouse, the neurotoxic effects of ATR appear to cause transient neurochemical alterations, whereas the loss of TH+ neurons appears to be persistent, possibly confined to basal ganglia dopaminergic neurons, but not exclusive to the SNpc.

摘要

除草剂阿特拉津(ATR)是美国一种非常常用的杀虫剂,也是一种主要的地下水污染物。最近,它还被认为是一种潜在的基底神经节毒物。在本研究中,我们的目的是确定ATR暴露对雄性幼年C57BL/6小鼠纹状体神经化学、黑质致密部(SNpc)多巴胺能神经元数量的影响,并作为参考,观察其对腹侧被盖区(VTA)的影响。口服ATR 14天,在治疗后长达一周的时间里,纹状体中多巴胺(DA)及其代谢产物的水平呈剂量依赖性下降。ATR暴露还使SNpc和VTA中酪氨酸羟化酶阳性(TH+)多巴胺能神经元的数量呈时间和剂量依赖性减少(在SNpc中的影响略为明显),以至于在停止暴露于ATR后7周时,这种减少最为明显。总之,这些数据表明,在幼年雄性C57BL/6小鼠中,ATR的神经毒性作用似乎会引起短暂的神经化学改变,而TH+神经元的丧失似乎是持续性的,可能局限于基底神经节多巴胺能神经元,但并非仅限于SNpc。

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