Imidacloprid induces neurobehavioral deficits and increases expression of glial fibrillary acidic protein in the motor cortex and hippocampus in offspring rats following in utero exposure
Imidacloprid induces neurobehavioral deficits and increases expression of glial fibrillary acidic protein in the motor cortex and hippocampus in offspring rats following in utero exposure
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DOI：
10.1080/15287390701613140
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发表时间：
2008-01-01
影响因子：
2.6
通讯作者：
Abdel-Rahman, Ali A.
中科院分区：
文献类型：
--
作者：
Abou-Donia, Mohamed B.;Goldstein, Larry B.;Abdel-Rahman, Ali A.
吡虫啉是一种烟碱类杀虫剂，由于其对昆虫的选择性，是全球使用增长最快的杀虫剂之一。尚不清楚子宫内暴露于吡虫啉后神经毒性的可能性。在妊娠第9天对定时妊娠Sprague-Dawley大鼠（300-350 g）单次腹腔注射（ip）吡虫啉（337 mg/kg，0.75 x LD 50，溶于玉米油）。对照组大鼠用玉米油处理。在出生后第30天（PND），评价所有雄性和雌性后代的（a）乙酰胆碱酯酶（ACNE）和丁酰胆碱酯酶（BuChE）活性，（B）烟碱型乙酰胆碱受体（nAChR）和毒蕈碱型乙酰胆碱受体的配体结合，（m2 mAChR），（c）感觉运动性能（d）脑中的病理改变（使用甲酚紫和胶质细胞酸性蛋白[GFAP]免疫染色）。在行为评估期间，给药母体的后代在PND 30时表现出显著的感觉运动障碍。这些变化与中脑、皮质和脑干（增加125-145%）以及血浆（增加125%）中的ACNE活性增加相关。α 4 β 2型nAchR的[H-3]胞嘧啶的配体结合密度未显示任何显著变化，而[3 H]AFDX 384（m2mAChR的配体）在吡虫啉处理母体的后代皮质中显著增加（增加120-155%）。使用甲酚紫染色的组织学评价未显示不同脑区中存活神经元的任何改变。另一方面，在运动皮层第三层，CA 1，CA 3，和海马齿状回子区的吡虫啉处理的母亲的后代的GFAP免疫染色的上升。结果表明，妊娠期暴露于一个单一的大，非致死剂量的吡虫啉产生显着的神经行为缺陷和增加的表达GFAP在几个脑区的后代PND 30，对应于人类青春期早期的年龄。这些变化可能对后代的健康产生长期不利影响。
Imidacloprid, a neonicotinoid, is one of the fastest growing insecticides in use worldwide because of its selectivity for insects. The potential for neurotoxicity following in utero exposure to imidacloprid is not known. Timed pregnant Sprague-Dawley rats (300-350 g) on d 9 of gestation were treated with a single intraperitoneal injection (ip) of imidacloprid (337 mg/kg, 0.75 x LD50, in corn oil). Control rats were treated with corn oil. On postnatal day (PND) 30, all male and female offspring were evaluated for (a) acetylcholinesterase (ACNE) and butyrylcholinesterase (BuChE) activity, (b) ligand binding for nicotinic acetylcholine receptors (nAChR) and muscarinic acetylcholine receptors (m2 mAChR), (c) sensorimotor performance (inclined plane, beam-walking, and forepaw grip), and (d) pathological alterations in the brain (using cresyl violet and glial fibrillary acidic protein [GFAP] immunostaining). The offspring of treated mothers exhibited significant sensorimotor impairments at PND 30 during behavioral assessments. These changes were associated with increased ACNE activity in the midbrain, cortex and brainstem (125-145% increase) and in plasma (125% increase). Ligand binding densities for [H-3]cytosine for alpha 4 beta 2 type nAchR did not show any significant change, whereas [3H]AFDX 384, a ligand for m2mAChR, was significantly increased in the cortex of offspring (120-155% increase) of imidacloprid-treated mothers. Histopathological evaluation using cresyl violet staining did not show any alteration in surviving neurons in various brain regions. On the other hand, there was a rise in GFAP immunostaining in motor cortex layer III, CA1, CA3, and the dentate gyrus subfield of the hippocampus of offspring of imidacloprid-treated mothers. The results indicate that gestational exposure to a single large, nonlethal, dose of imidacloprid produces significant neurobehavioral deficits and an increased expression of GFAP in several brain regions of the offspring on PND 30, corresponding to a human early adolescent age. These changes may have long-term adverse health effects in the offspring.