Epidemiological evidences have shown an association of exposure to pesticides or heavy metals with increased incidences of Parkinson's disease (PD) in humans. Exposure to pesticides or metals during the decisive period of the brain development increases the susceptibility of dopaminergic neurons upon re-exposure in adult rodents. However, the effect of early life exposure to pesticide on the heavy metal-induced neurodegeneration or heavy metal on pesticide-induced neurodegeneration is not yet explored. The current study explored the effect of developmental exposure to zinc (Zn), a metal or paraquat (PQ), a pesticide on the nigrostriatal dopaminergic neurons of rats challenged to Zn or PQ during adulthood. Exposure of Zn or PQ during adulthood alone exhibited marked reduction in motor activities, striatal dopamine and metabolites, glutathione content and number of dopaminergic neurons. However, the levels of lipid peroxidation, protein carbonyls, superoxide dismutase activity, pro-inflammatory cytokines and 4-hydroxynonenal-protein adducts were increased. While the expression of vesicular monoamine transporter-2 and tyrosine hydroxylase were attenuated, dopamine transporter and microglial marker Iba-1 expression, activated microglia, nuclear factor-kappa B activation, mitochondrial cytochrome c release and caspase-3/9 activation were augmented following Zn or PQ exposure. Albeit postnatal alone exposure did not alter any of the studied parameters, the developmental administration of Zn/PQ in re-challenged adult rats produced more pronounced changes in the aforementioned variables as compared with adulthood Zn or PQ alone intoxicated animals. The results demonstrate that postnatal Zn/PQ intoxication dents the oxidative stress, inflammation, cell death and dopamine metabolism and storage regulating machineries, which speed up the toxicant-induced degeneration during adulthood.

中文翻译：

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产后服用锌或百草枯会增加百草枯或锌引起的多巴胺能神经元的损失：深入了解神经变性。

流行病学证据表明，暴露于农药或重金属与人类帕金森氏病（PD）发病率增加相关。在成年鼠中再次暴露后，在大脑发育的决定性时期内暴露于农药或金属会增加多巴胺能神经元的敏感性。然而，尚未探索早期接触农药对重金属诱导的神经变性或农药对重金属引起的神经变性的影响。当前的研究探讨了发育暴露于金属中的锌或锌，一种金属或百草枯，一种农药对成年期受到Zn或PQ攻击的大鼠的黑质纹状体多巴胺能神经元的影响。仅在成年期锌或PQ的暴露就显示出运动活动，纹状体多巴胺和代谢产物的明显减少，谷胱甘肽含量和多巴胺能神经元的数量。然而，脂质过氧化，蛋白质羰基，超氧化物歧化酶活性，促炎性细胞因子和4-羟基壬醛-蛋白质加合物的水平增加。锌后，虽然水泡单胺转运蛋白2和酪氨酸羟化酶的表达减弱，但多巴胺转运蛋白和微胶质标记物Iba-1的表达，小胶质细胞活化，核因子-κB活化，线粒体细胞色素c释放和caspase-3 / 9活化增加。或PQ曝光。尽管出生后单独接触并没有改变任何研究参数，但与成年期单独使用Zn或PQ的中毒动物相比，重新挑战成年大鼠中Zn / PQ的发育性给药在上述变量中​​产生了更明显的变化。