Arsenic-Induced Neurotoxicity by Dysfunctioning Cholinergic and Dopaminergic System in Brain of Developing Rats
Arsenic-Induced Neurotoxicity by Dysfunctioning Cholinergic and Dopaminergic System in Brain of Developing Rats
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DOI：
10.1007/s12011-018-1452-5
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发表时间：
2019-05-01
影响因子：
3.9
通讯作者：
Shukla, Rajendra K.
中科院分区：
文献类型：
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作者：
Chandravanshi, Lalit P.;Gupta, Richa;Shukla, Rajendra K.
假定通过地球仪饮用水长期接触砷会导致发育神经毒性。在这里，我们研究了围产期砷暴露对纹状体，额叶皮质和海马神经行为和神经化学变化的影响，这些变化与运动和认知功能密切相关。本研究在以往研究的基础上，进一步证实了围产期（GD 6-PD 21）砷暴露（2或4 mg/kg体重，p.o.）导致砷暴露大鼠PD 22活动降低。研究发现，活性低下与DA-D2受体mRNA和蛋白质表达的减少有关。此外，酪氨酸羟化酶（TH）的蛋白质表达，多巴胺的水平，及其代谢产物也显着受损的纹状体。砷暴露组的空间学习和记忆能力明显低于对照组的平均水平，且呈剂量依赖性。在此，我们评估了CHRM 2受体基因表达和ChAT，PKC-1在额叶皮层和海马中的蛋白表达的下降，这与包括学习和记忆在内的认知功能密切相关。恢复的趋势被发现在胆碱能和多巴胺能系统的大脑，但变化仍然持续，即使在砷暴露的PD 45撤出。两者合计，我们的研究结果表明，围产期砷暴露似乎是关键和脆弱的胆碱能和多巴胺能系统的发展继续在此期间。
Chronic exposure to arsenic via drinking water throughout the globe is assumed to cause a developmental neurotoxicity. Here, we investigated the effect of perinatal arsenic exposure on the neurobehavioral and neurochemical changes in the corpus striatum, frontal cortex, and hippocampus that is critically involved in motor and cognition functions. In continuation of previous studies, this study demonstrates that perinatal exposures (GD6-PD21) to arsenic (2 or 4mg/kg body weight, p.o.) cause hypo-activity in arsenic-exposed rats on PD22. The hypo-activity was found to be linked with a decrease in the mRNA and protein expression of the DA-D2 receptor. Further, a protein expression of tyrosine hydroxylase (TH), levels of dopamine, and its metabolites were also significantly impaired in corpus striatum. The arsenic-exposed groups showed spatial learning and memory significantly below the average in a dose-dependent manner for the controls. Here, we evaluated the declined expression of CHRM2 receptor gene and protein expression of ChAT, PKC-1 in the frontal cortex and hippocampus, which are critically involved in cognition functions including learning and memory. A trend of recovery was found in the cholinergic and dopaminergic system of the brain, but changes remained persisted even after the withdrawal of arsenic exposure on PD45. Taken together, our results indicate that perinatal arsenic exposure appears to be critical and vulnerable as the development of cholinergic and dopaminergic system continues during this period.