Transplacental neurotoxicity of cypermethrin induced astrogliosis, microgliosis and depletion of let-7 miRNAs expression in the developing rat cerebral cortex

氯氰菊酯的胎盘神经毒性可诱导发育中大鼠大脑皮层星形胶质细胞增生、小胶质细胞增生以及let-7 miRNA表达降低

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Abstract

The use of type II pyrethroids, cypermethrin is becoming a growing concern among environmental research centers. While most studies have attempted to cover the areas of DNA damage and microglia activation following exposure to cypermethin in the adult or postnatal life, less is known about the exact degree of neurotoxicity that results from exposure to transplacental sublethal doses of cypermethrin. To study the transplacental neurotoxicity of cypermethrin, pregnant rats were orally administered 10 % of LD(50) (25 mg/kg body weight) cypermethrin, one dose daily for one week during the gestational days 15-21. The pups were investigated at postnatal day7, 14 and 21 after birth. In brain, DNA alterations were detected, astrocytes and microglia quantification were performed and some let7 family member miRNAs are estimated. The results show a gain of three major bands in the range of 350bp to 2100bp with high intensities in cortex exposed to cypermethrin compared with similar pattern indicating unaffected genomic regions in thalamus and hypothalamus at 21days. Moreover, increases in the percentage of GFAP positive astrocytes and IBA1 positive microglia indicate astrogliosis and microgliosis respectively due to cypermethrin treatment in cerebral cortex. For the first time, drastically reduced expression of let7a, b and c members are also associated with gliosis and DNA alterations, which are detected in cerebral cortex, following transplacental neurotoxicity of cypermethrin. Taking together, these results suggest that cypermethrin neurotoxicity may be mediated partly through let7 miRNAs.

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