Singh Anshuman, Mudawal Anubha, Shukla Rajendra K, Yadav Sanjay, Khanna Vinay K, Sethumadhavan Rao, Parmar Devendra
Developmental Toxicology Division, CSIR-Indian Institute of Toxicology Research, Post Box No. 80, M.G. Marg, Lucknow, 226001, Uttar Pradesh, India,
Mol Neurobiol. 2015 Aug;52(1):741-56. doi: 10.1007/s12035-014-8903-6. Epub 2014 Oct 7.
Oral administration of low doses (1.25, 2.5, or 5 mg/kg) of cypermethrin to pregnant Wistar rats from gestation days 5 to 21 led to dose-dependent differences in the induction of cytochrome P450 2D1 (CYP2D1) and 3A1 messenger RNA (mRNA) and protein in brain regions isolated from the offsprings postnatally at 3 weeks that persisted up to adulthood (12 weeks). Similar alterations were observed in the expression of GABAergic, muscarinic, dopaminergic, and serotonergic neurotransmitter receptors in brain regions of rat offsprings. Rechallenge of the prenatally exposed offsprings at adulthood (12 weeks old) with cypermethrin (p.o., 10 mg/kg for 6 days) led to a greater magnitude of alterations in the expression of CYPs, neurotransmitter receptors, and neurotransmitter receptor binding in the brain regions when compared to the control offsprings treated at adulthood with cypermethrin or prenatally exposed offsprings. A greater magnitude of decrease was also observed in the spontaneous locomotor activity (SLA) in prenatally exposed offsprings rechallenged with cypermethrin. The present data indicating similarities in the alterations in the expression of CYPs (2D1 and 3A1) and neurotransmitter receptors in brain has led us to suggest that endogenous function regulating CYPs is possibly associated with neurotransmission processes. A greater magnitude of alterations in CYP2D1, 3A1, neurotransmitter receptors, and SLA in rechallenged animals has further provided evidence that alterations in CYPs are possibly linked with neurotransmission processes.
从妊娠第5天至21天给怀孕的Wistar大鼠口服低剂量（1.25、2.5或5毫克/千克）的氯氰菊酯，导致出生后3周从后代分离的脑区中细胞色素P450 2D1（CYP2D1）和3A1信使核糖核酸（mRNA）及蛋白质的诱导出现剂量依赖性差异，这些差异一直持续到成年期（12周）。在大鼠后代脑区的γ-氨基丁酸能、毒蕈碱能、多巴胺能和5-羟色胺能神经递质受体的表达中也观察到了类似变化。成年期（12周龄）对产前暴露的后代再次用氯氰菊酯（口服，10毫克/千克，持续6天）进行激发，与成年期用氯氰菊酯处理的对照后代或产前暴露的后代相比，导致脑区中细胞色素P450、神经递质受体和神经递质受体结合的表达变化幅度更大。在用氯氰菊酯再次激发的产前暴露后代中，自发运动活动（SLA）也出现了更大幅度的下降。目前的数据表明，脑区中细胞色素P450（2D1和3A1）和神经递质受体表达的变化具有相似性，这使我们认为调节细胞色素P450的内源性功能可能与神经传递过程有关。再次激发的动物中CYP2D1、3A1、神经递质受体和SLA的变化幅度更大，这进一步证明了细胞色素P450的变化可能与神经传递过程有关。
