Early life permethrin exposure induces long-term brain changes in Nurr1, NF-kB and Nrf-2
Early life permethrin exposure induces long-term brain changes in Nurr1, NF-kB and Nrf-2
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DOI：
10.1016/j.brainres.2013.03.048
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发表时间：
2013-06-17
期刊：
影响因子：
2.9
通讯作者：
Gabbianelli, Rosita
中科院分区：
文献类型：
--
作者：
Carloni, Manuel;Nasuti, Cinzia;Gabbianelli, Rosita
在大脑发育期间接触农药是大脑老化过程开始的一个重要风险因素。在此，当动物达到500日龄时，研究了以接近“无明显不良作用水平”（NOAEL）的剂量从出生后第6天至第21天对大鼠给予氯菊酯的影响。氯菊酯处理诱导纹状体Nurr 1基因表达减少，海马和小脑增加，而蛋白质水平仅在纹状体增加。与对照组相比，治疗组大鼠小脑NF-κ B p65基因表达增加，小脑和前额叶皮质NF-κ B p65蛋白表达增加，海马NF-κ B p65蛋白表达减少。NRF-2基因表达仅在治疗动物的小脑中显著升高。结果表明，早期的生命氯菊酯治疗诱导持久的影响，导致多巴胺能神经元疾病，监测Nurr 1改变。此外，NF-kB和Nrf-2的损伤，对亲和亲系统之间的平衡很重要，证实了新生儿氯菊酯治疗可以影响与脑老化过程的发生有关的基因。(C)2013爱思唯尔有限公司版权所有。
Pesticide exposure during brain development represents an important risk factor for the onset of brain-aging processes. Here, the impact of permethrin administered to rats from 6th to 21st day of life, at a dose near to "no observed adverse effect level" (NOAEL), was studied when animals reached 500 day-old. The permethrin treatment induced a decrease in Nurr1 gene expression in striatum, an increase in hippocampus and cerebellum, while the protein level changed only in striatum where it was increased. NF-kB p65 gene expression was increased in cerebellum, while its protein level augmented in cerebellum and in prefrontal cortex and decreased in hippocampus of treated rats compared to control ones. Nrf-2 gene expression resulted significantly higher only in cerebellum of treated animals. The results suggest that early life permethrin treatment induces long-lasting effects leading to dopaminergic neuronal disorders, monitored by Nurr1 alteration. Moreover the impairment of NF-kB and Nrf-2, important for the balance between pro- and antiinflammatory systems, confirms that the neonatal permethrin treatment can influence genes involved with the onset of brain-ageing processes. (C) 2013 Elsevier B.V. All rights reserved.