Abou-Donia Mohamed B, Goldstein Larry B, Bullman Sarah, Tu T, Khan Wasi A, Dechkovskaia Ankelika M, Abdel-Rahman Ali A
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
J Toxicol Environ Health A. 2008;71(2):119-30. doi: 10.1080/15287390701613140.
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 (i.p.) 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 (AChE) 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 AChE activity in the midbrain, cortex and brainstem (125-145% increase) and in plasma (125% increase). Ligand binding densities for [3H]cytosine for alpha4beta2 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.
吡虫啉是一种新烟碱类杀虫剂，由于其对昆虫的选择性，它是全球使用量增长最快的杀虫剂之一。子宫内暴露于吡虫啉后的神经毒性潜力尚不清楚。在妊娠第9天，对体重300 - 350克的定时受孕斯普拉格-道利大鼠进行单次腹腔注射（i.p.）吡虫啉（337毫克/千克，0.75×半数致死剂量，溶于玉米油）。对照大鼠注射玉米油。在出生后第30天（PND 30），对所有雄性和雌性后代进行以下评估：（a）乙酰胆碱酯酶（AChE）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（m2 mAChR）的配体结合；（c）感觉运动性能（斜面试验、走梁试验和前爪抓握试验）；（d）大脑的病理改变（使用甲酚紫和胶质纤维酸性蛋白[GFAP]免疫染色）。在行为评估中，经处理的母亲的后代在出生后第30天表现出明显的感觉运动障碍。这些变化与中脑、皮层和脑干中AChE活性增加（增加125 - 145%）以及血浆中AChE活性增加（增加125%）有关。α4β2型nAchR的[3H]胞嘧啶配体结合密度没有显示出任何显著变化，而m2mAChR的配体[3H]AFDX 384在吡虫啉处理的母亲的后代皮层中显著增加（增加120 - 155%）。使用甲酚紫染色的组织病理学评估未显示不同脑区存活神经元有任何改变。另一方面，吡虫啉处理的母亲的后代的运动皮层III层、海马体的CA1、CA3和齿状回亚区的GFAP免疫染色增加。结果表明，孕期单次暴露于大剂量、非致死剂量的吡虫啉会导致明显的神经行为缺陷，并使出生后第30天后代的几个脑区中GFAP表达增加，这相当于人类青少年早期年龄。这些变化可能会对后代产生长期的不良健康影响。
