孕期暴露于高效氯氟氰菊酯会改变发育中大鼠的脑多巴胺能信号传导。
Prenatal exposure to lambda-cyhalothrin alters brain dopaminergic signaling in developing rats.
作者信息
Dhuriya Yogesh K, Srivastava Pranay, Shukla Rajendra K, Gupta Richa, Singh Dhirendra, Parmar Devendra, Pant Aditya B, Khanna Vinay K
机构信息
Developmental Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow - 226001, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), Lucknow Campus, India.
Developmental Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow - 226001, Uttar Pradesh, India.
出版信息
Toxicology. 2017 Jul 1;386:49-59. doi: 10.1016/j.tox.2017.04.014. Epub 2017 May 8.
The present study is focused to decipher the molecular mechanisms associated with dopaminergic alterations in corpus striatum of developing rats exposed prenatally to lambda-cyhalothrin (LCT), a new generation type II synthetic pyrethroid. There was no significant change in the mRNA and protein expression of DA-D1 receptors at any of the doses of LCT (0.5, 1 and 3mg/kg body weight) in corpus striatum of developing rats exposed prenatally to LCT on PD22 and PD45. Prenatal exposure to LCT (1 and 3mg/kg body weight) resulted to decrease the levels of mRNA and protein of DA-D2 receptors in corpus stratum of developing rats on PD22 as compared to controls. Decrease in the binding of 3H-Spiperone in corpus striatum, known to label DA-D2 receptors was also distinct in developing rats on PD22. These rats also exhibited decrease in the expression of proteins - TH, DAT and VMAT2 involved in pre-dopaminergic signaling. Further, decrease in the expression of DARPP-32 and pCREB associated with increased expression of PP1α was evident in developing rats on PD22 as compared to controls. Interestingly, a trend of recovery in the expression of these proteins was observed in developing rats exposed to LCT at moderate dose (1.0mg/kg body weight) while alteration in the expression of these proteins continued to persist in those exposed at high dose (3.0mg/kg body weight) on PD45 as compared to respective controls. No significant change in the expression of any of these proteins was observed in corpus striatum of developing rats prenatally exposed to LCT at low dose (0.5mg/kg body weight) on PD22 and PD45 as compared to respective controls. The results provide interesting evidence that alterations in dopaminergic signaling on LCT exposure are due to selective changes in DA-D2 receptors in corpus striatum of developing rats. Further, these changes could be attributed to impairment in spontaneous motor activity on LCT exposure in developing rats.
本研究旨在阐明产前暴露于高效氯氟氰菊酯（LCT，一种新一代II型合成拟除虫菊酯）的发育中大鼠纹状体中多巴胺能改变相关的分子机制。产前暴露于LCT的发育中大鼠在出生后第22天（PD22）和第45天（PD45）时，纹状体中任何剂量的LCT（0.5、1和3mg/kg体重）均未使DA-D1受体的mRNA和蛋白表达发生显著变化。与对照组相比，产前暴露于LCT（1和3mg/kg体重）导致PD22时发育中大鼠纹状体中DA-D2受体的mRNA和蛋白水平降低。已知可标记DA-D2受体的3H-螺哌隆在纹状体中的结合减少在PD22的发育中大鼠中也很明显。这些大鼠还表现出参与多巴胺能前信号传导的蛋白质——酪氨酸羟化酶（TH）、多巴胺转运体（DAT）和囊泡单胺转运体2（VMAT2）的表达降低。此外，与对照组相比，PD22时发育中大鼠中与蛋白磷酸酶1α（PP1α）表达增加相关的多巴胺和腺苷酸环化酶调节蛋白（DARPP-32）和磷酸化环磷腺苷反应元件结合蛋白（pCREB）的表达降低明显。有趣的是，在中等剂量（1.0mg/kg体重）暴露于LCT的发育中大鼠中观察到这些蛋白表达有恢复趋势，而在PD45时，与各自对照组相比，高剂量（3.0mg/kg体重）暴露的大鼠中这些蛋白的表达变化仍持续存在。与各自对照组相比，产前低剂量（0.5mg/kg体重）暴露于LCT的发育中大鼠在PD22和PD45时纹状体中这些蛋白的表达均未发生显著变化。结果提供了有趣的证据，表明暴露于LCT时多巴胺能信号的改变是由于发育中大鼠纹状体中DA-D2受体的选择性变化。此外，这些变化可能归因于发育中大鼠暴露于LCT时自发运动活动受损。
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