Division of Forensic Science, School of Basic and Applied Sciences, Galgotias University, Greater Noida, 201307, India.
Developmental Toxicology Division, CSIR-Indian Institute of Toxicology Research, Post Box No. 80, MG Marg, Lucknow, 226 001, India.
Biol Trace Elem Res. 2019 May;189(1):118-133. doi: 10.1007/s12011-018-1452-5. Epub 2018 Jul 26.
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 4 mg/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, PKCβ-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.
全球范围内，通过饮用水慢性暴露于砷被认为会导致发育性神经毒性。在这里，我们研究了围产期砷暴露对与运动和认知功能密切相关的纹状体、额叶皮层和海马神经行为和神经化学变化的影响。在之前研究的基础上，本研究表明，围产期（GD6-PD21）暴露于砷（2 或 4mg/kg 体重，口服）会导致暴露于砷的大鼠在 PD22 时活动减少。这种活动减少与 DA-D2 受体的 mRNA 和蛋白表达减少有关。此外，纹状体中酪氨酸羟化酶（TH）的蛋白表达、多巴胺及其代谢物的水平也显著受损。暴露于砷的组表现出空间学习和记忆能力显著低于对照组，呈剂量依赖性。在这里，我们评估了 CHRM2 受体基因和 ChAT、PKCβ-1 的蛋白表达在额叶皮层和海马中的表达下降，这些受体和蛋白在认知功能（包括学习和记忆）中起着至关重要的作用。在大脑的胆碱能和多巴胺能系统中发现了一种恢复的趋势，但即使在 PD45 停止暴露于砷后，变化仍然持续存在。总之，我们的结果表明，围产期砷暴露似乎是关键的，易受影响的，因为在此期间，胆碱能和多巴胺能系统的发育仍在继续。
