Neuroimmunology and Neurochemistry Research Group, Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hauptstr. 5, D-79104 Freiburg, Germany; Laboratory of Toxicology-Microbiology and Environmental Health, UR17ES06, Sciences Faculty of Sfax, University of Sfax, BP1171, 3000 Sfax, Tunisia.
Department of Environmental and Occupational Health, Chair in Toxicological Risk Assessment and Management, University of Montreal, Roger-Gaudry Building, U424, P.O. Box 6128, Main Station, Montreal, Quebec, H3C 3J7, Canada.
Behav Brain Res. 2019 Sep 16;370:111898. doi: 10.1016/j.bbr.2019.04.012. Epub 2019 Apr 9.
Exposure to insecticides has been associated with depression-like symptoms, especially among occupationally exposed populations, such as farmers. Although the neurotoxicity of pyrethroids such as bifenthrin (BF) is well established, it is still unclear whether exposure to BF may have deleterious effects on the hippocampus and thus behavior. We verified the hypothesis that repeated exposure to BF in a rat model elicits neurochemical and behavioral alterations, the latter of which reflects depression-related symptoms. Adult male Wistar rats (n = 12 per group) were orally administered with different doses of BF (0.6 or 2.1 mg/kg body weight (b.w.)) on a daily basis for 60 days; control rats received the vehicle (corn oil). Different biochemical changes were assessed in the hippocampus, a region of the brain regulating spatial memory; behavioral tests were also conducted. Our results revealed depressive-like behaviors that were expressed by increased despair behavior in the Forced-swimming test. Repeated exposure to BF also decreased acetylcholinesterase (AChE) activity in the hippocampus and butyrylcholinesterase (BuChE) activity in plasma. A significant reduction in the activities of hippocampal membrane-bound ATPases (Na/K-ATPase and Mg-ATPase) was also observed in BF-treated rats compared to controls. Furthermore, a significant decrease in mRNA expression and protein synthesis of both AChE and orphan nuclear receptor (Nurr-1), as well as in the expression of muscarinic-cholinergic receptor (M1 mAchR) and nicotinic-cholinergic receptor (nAchR2α) was observed in the hippocampus of treated rats compared to controls. Also, BF exposure induced apoptosis as assessed by hippocampal Casp-3 protein levels. Our findings suggest that repeated exposure to BF affects hippocampal signaling and Nurr-1/AChE, and this was accompanied by depression-like state in adult rats.
接触杀虫剂与抑郁样症状有关，尤其是在职业接触人群中，如农民。尽管拟除虫菊酯（如溴氰菊酯）的神经毒性已得到充分证实，但接触溴氰菊酯是否会对海马体产生有害影响，从而影响行为，目前仍不清楚。我们验证了以下假设，即在大鼠模型中重复接触溴氰菊酯会引起神经化学和行为改变，后者反映了与抑郁相关的症状。成年雄性 Wistar 大鼠（每组 12 只）每天口服不同剂量的溴氰菊酯（0.6 或 2.1mg/kg 体重），持续 60 天；对照组大鼠给予载体（玉米油）。评估了海马体中的不同生化变化，海马体是调节空间记忆的大脑区域；还进行了行为测试。我们的结果显示，在强迫游泳测试中，大鼠表现出绝望行为增加，表明出现了抑郁样行为。重复接触溴氰菊酯还降低了海马体中的乙酰胆碱酯酶（AChE）活性和血浆中的丁酰胆碱酯酶（BuChE）活性。与对照组相比，还观察到 BF 处理大鼠海马体膜结合 ATP 酶（Na/K-ATP 酶和 Mg-ATP 酶）的活性显著降低。此外，与对照组相比，BF 处理大鼠海马体中 AChE 和孤儿核受体（Nurr-1）的 mRNA 表达和蛋白合成以及毒蕈碱型乙酰胆碱受体（M1 mAchR）和烟碱型乙酰胆碱受体（nAchR2α）的表达均显著降低。此外，通过海马体 Caspase-3 蛋白水平评估，发现 BF 暴露会诱导细胞凋亡。我们的研究结果表明，重复接触溴氰菊酯会影响海马体信号传导和 Nurr-1/AChE，并且这伴随着成年大鼠出现抑郁样状态。
