School of Pharmacy and Health Science, International Medical University, No. 126, Jalan 19/155B, Bukit Jalil, 57000 Kuala Lumpur, Malaysia.
J Neural Transm (Vienna). 2012 Mar;119(3):345-52. doi: 10.1007/s00702-011-0715-5. Epub 2011 Sep 16.
Chlorpyrifos (CPF), an organophosphate pesticide inhibits acetylcholinesterase (AChE) and causes neuromuscular incoordination among children and elderly. The objectives of the present study were to compare the neurotoxic effects of dermal application of CPF on the cerebellum in the parameters of glial fibrillary acidic protein (GFAP) expression in young and adult mice and to correlate with the changes in acetylcholinesterase levels. Male Balb/c mice, 150 days old (adult) and 18 days old (young) were dermally applied with ½ LD(50) of CPF over the tails for 14 days. Serum AChE concentration was estimated and GFAP immunostaining was performed on sagittal paraffin sections through the vermis of cerebellum. Although reduced in both age-groups exposed to CPF, percentage of reduction in serum AChE was more in adult compared to the young. Under GFAP immunostaining, brown colour fibres and glial cells were observed in cerebellar cortex and medulla in both the experimental groups. The mean GFAP-positive glial cell count in cerebellar medulla per mm(2) of section was significantly (p < 0.05) increased in adult mice exposed to CPF when compared with age-matched control. In conclusion, this study confirmed that dermal exposure of CPF was able to exert neurotoxic effect in both young and adult mice. However, the quantitative results revealed that adult mice showed more GFAP expression in cerebellum when compared with the young, when exposed to CPF.
毒死蜱（CPF）是一种有机磷农药，它会抑制乙酰胆碱酯酶（AChE）的活性，导致儿童和老年人出现神经肌肉协调障碍。本研究的目的是比较 CPF 经皮涂抹对幼鼠和成年鼠小脑内神经毒性的影响，通过测定胶质纤维酸性蛋白（GFAP）的表达，来评估其对神经的毒性作用，并与乙酰胆碱酯酶（AChE）水平的变化相关联。雄性 Balb/c 幼鼠（18 日龄，幼鼠）和成年鼠（150 日龄）在尾巴上涂抹半致死剂量（LD50）的 CPF 14 天。检测血清中 AChE 浓度，对小脑蚓部矢状石蜡切片进行 GFAP 免疫染色。尽管 CPF 暴露组的血清 AChE 浓度均降低，但成年鼠的降低程度明显大于幼鼠。在 GFAP 免疫染色中，在小脑皮质和髓质中都观察到棕褐色的纤维和神经胶质细胞。CPF 暴露的成年鼠小脑髓质内每平方毫米（mm2）GFAP 阳性胶质细胞计数明显高于年龄匹配的对照组（p < 0.05）。结论：本研究证实 CPF 经皮暴露可对幼鼠和成年鼠均产生神经毒性作用。然而，定量结果表明，与幼鼠相比，成年鼠在接触 CPF 时，小脑内的 GFAP 表达更多。
