Peris-Sampedro Fiona, Salazar José G, Cabré Maria, Reverte Ingrid, Domingo José L, Sánchez-Santed Fernando, Colomina Maria Teresa
Department of Psychology and Research Center for Behavior Assessment (CRAMC), Universitat Rovira i Virgili, Tarragona, Spain; Research in Neurobehavior and Health (NEUROLAB), Universitat Rovira i Virgili, Tarragona, Spain; Laboratory of Toxicology and Environmental Health, School of Medicine, IISPV, Universitat Rovira i Virgili, Reus, Spain.
Research in Neurobehavior and Health (NEUROLAB), Universitat Rovira i Virgili, Tarragona, Spain; Department of Toxicology and Pharmacology, University of Los Andes, Merida, Venezuela.
Food Chem Toxicol. 2014 Oct;72:289-94. doi: 10.1016/j.fct.2014.07.036. Epub 2014 Aug 8.
Chlorpyrifos (CPF) is an organophosphate pesticide. This pesticide induces cognitive impairments, oxidative stress and neuronal damage, which suggests a possible relationship between CPF exposure and Alzheimer's disease. In this study we examined long-term changes in behavior and brain levels of the amyloid beta (Aβ) protein after repeated CPF exposure in a mouse model of Alzheimer's disease. Tg2576 male mice between four and six months of age carrying the human Swedish mutation for Alzheimer's disease were exposed to eight doses of 25 mg/kg of CPF distributed over four weeks. Five months after exposure, general activity was measured in an open-field, while learning and memory were assessed in a Morris water maze task six months after treatment with CPF. Levels of the Aβ fragments (1-40 and 1-42) were also measured in the frontal cortex and hippocampal brain regions. Motor activity was increased in CPF-exposed mice. Although acquisition learning in a water maze task was not affected, retention was worsened in CPF-exposed mice. There were no significant increases of Aβ levels in the brains of CPF-treated mice six months after exposure. These findings raise concerns about the risk of developing neurodegenerative diseases in vulnerable subjects following repeated exposure to CPF.
毒死蜱（CPF）是一种有机磷农药。这种农药会导致认知障碍、氧化应激和神经元损伤，这表明接触CPF与阿尔茨海默病之间可能存在关联。在本研究中，我们在阿尔茨海默病小鼠模型中检测了重复接触CPF后行为和大脑中β淀粉样蛋白（Aβ）水平的长期变化。对携带人类阿尔茨海默病瑞典突变的4至6月龄Tg2576雄性小鼠，在四周内分八次给予25mg/kg的CPF。接触后五个月，在旷场中测量一般活动，而在给予CPF治疗六个月后，在莫里斯水迷宫任务中评估学习和记忆。还测量了额叶皮质和海马脑区中Aβ片段（1-40和1-42）的水平。接触CPF的小鼠运动活动增加。虽然水迷宫任务中的习得性学习未受影响，但接触CPF的小鼠的记忆保持能力变差。接触后六个月，CPF处理小鼠大脑中的Aβ水平没有显著升高。这些发现引发了人们对易感人群反复接触CPF后患神经退行性疾病风险的担忧。
