Abstract

This study investigated the exposure of pyrethroids in the development of Alzheimer’s type neurodegeneration by analyzing β- amyloid, tau and Glial Fibrillary Acidic Protein (GFAP) in adult Wistar rats. Forty adult Wistar rats (130–150 g) of both sexes were assigned into five groups (n = 8). Groups A-C were treated with three different sub-lethal doses (75, 50 and 25%)of the pyrethroids formulation diluted with olive oil once/daily for 45 days, while groups D&E received olive oil and distilled water respectively (as control groups). During the treatments, physical clinical signs were monitored for cognitive behavioral studies involving object recognition tasks and novel object identification test. At the end of treatment, the rats were sacrificed by cervical dislocation, the brains were harvested and the hippocampus located and dissected out for immunohistochemical studies. Standard histochemical techniques were employed. The results showed a significant decrease (p ≤ 0.05) in the spontaneous alternation and discrimination index in the treatment groups when compared to the control groups. Histological observation showed nuclear fragmentation in treated rats in a dose dependent manner when compared to the controls. Amyloid plaques were further observed and markedly stained with Congo-red in the treated rats compared to the control groups. Immunohistochemical observation revealed that exposure to pyrethroids increased immunoreactivity of GFAP and tau protein in both CA3 and Dentate gyrus (DG) regions in the treated rats indicative of Alzheimer’s type degenerative diseases.

摘要

本研究通过分析成年 Wistar 大鼠中的 β-淀粉样蛋白、tau 和胶质纤维酸性蛋白 (GFAP)，研究了拟除虫菊酯在阿尔茨海默病型神经退行性变发展过程中的暴露。将 40 只成年 Wistar 大鼠 (130-150 g) 分为五组 ( n = 8）。AC 组用三种不同的亚致死剂量（75%、50% 和 25%）的拟除虫菊酯制剂每天一次/每天一次用橄榄油稀释，持续 45 天，而 D&E 组分别接受橄榄油和蒸馏水（作为对照组）。在治疗期间，对涉及物体识别任务和新物体识别测试的认知行为研究监测身体临床症状。在治疗结束时，通过颈椎脱臼法处死大鼠，收获大脑并定位并解剖海马用于免疫组织化学研究。采用标准组织化学技术。结果显示显着下降（p ≤ 0.05) 与对照组相比，治疗组的自发交替和辨别指数。组织学观察显示，与对照组相比，治疗大鼠的核碎裂呈剂量依赖性。与对照组相比，在处理的大鼠中进一步观察到淀粉样蛋白斑块并用刚果红显着染色。免疫组织化学观察显示，在处理过的大鼠中，暴露于拟除虫菊酯会增加 CA3 和齿状回 (DG) 区域中 GFAP 和 tau 蛋白的免疫反应性，这表明阿尔茨海默病型退行性疾病。