Persistent diazinon induced neurotoxicity: The effect on inhibitory avoidance memory performance, amyloid precursor proteins, and TNF-α levels in the prefrontal cortex of rats.

Salva Afshari, Mehdi Sarailoo, Vahid Asghariazar, Elham Safarzadeh, Masoomeh Dadkhah
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Abstract

Introduction: Organophosphate pesticides (Ops) like diazinon (DZN) have well-known neurotoxic effects and low-level chronic exposure has been linked to detrimental neurobehavioral impairments and memory deficits. However, it's not entirely clear how DZN-induced biological changes, particularly in the prefrontal cortex (PFC) contribute to these effects. The purpose of this study is to investigate the impact of DZN exposure on inhibitory avoidance (IA) memory function, amyloid precursor expression (APP), and proinflammatory tumor necrosis factor-α (TNF-α) levels in the rat cortex.

Materials and methods: Rats were divided into 4 groups and recived 2 mg/kg DZN for 5-days or 12-weeks and two control groups recived the same volume of vehicle. IA memory was assesed using the shuttle box apparatus. Rats were sacrificed and the prefrontal cortex PFC were removed. Real-time PCR and Western blotting were used to messure TNF-α, and amyloid protein precursors gene expression and protein levels.

Results: Our findings indicated that DZN caused body weight loss and a notable decline in performance on the IA memory. Additionally, 5-days exposure increased APP and APLP2 protein levels in the PFC, while 12-weeks exposure decreased these levels. Furthermore, expression of APP and APLP2 gens were decreased in PFC. TNF-α levels increased as a result of 5-days exposure to DZN, but these levels dropped to normal after 12-weeks administration, and this observation was significant.

Conclusion: Taken together, exposure to low doses of DZN leads to disturbances in IA memory performance and also alternations in amyloid beta precursors that can be related to increased risk of Alzheimer's disease.

持续性二嗪农诱导的神经毒性:对大鼠前额叶皮层抑制性回避记忆能力、淀粉样前体蛋白和 TNF-α 水平的影响
简介:有机磷农药(Ops),如二嗪农(DZN),具有众所周知的神经毒性作用,低水平的慢性接触与有害的神经行为障碍和记忆缺陷有关。然而,目前还不完全清楚 DZN 引起的生物变化,尤其是前额叶皮层(PFC)的生物变化是如何导致这些影响的。本研究的目的是调查DZN暴露对大鼠大脑皮层抑制性回避(IA)记忆功能、淀粉样前体表达(APP)和促炎性肿瘤坏死因子-α(TNF-α)水平的影响:将大鼠分为 4 组,每组 2 毫克/千克 DZN,连续注射 5 天或 12 周。使用穿梭箱装置检测大鼠的 IA 记忆。大鼠被处死并切除前额叶皮层。采用实时 PCR 和 Western 印迹技术检测 TNF-α 和淀粉样蛋白前体的基因表达和蛋白水平:结果:我们的研究结果表明,DZN会导致体重减轻和IA记忆能力明显下降。此外,暴露5天会增加前脑功能区的APP和APLP2蛋白水平,而暴露12周则会降低这些水平。此外,APP和APLP2基因在PFC中的表达也有所下降。暴露于DZN 5天后,TNF-α水平升高,但在用药12周后,这些水平降至正常,且这一观察结果具有显著意义:综上所述,暴露于低剂量的DZN会导致IA记忆能力的紊乱,以及淀粉样β前体的交替,这可能与阿尔茨海默病风险的增加有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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