Rojo Ana I, Cavada Carmen, de Sagarra María Rosa, Cuadrado Antonio
Instituto de Investigaciones Biomédicas, Departamento de Bioquímica Facultad de Medicina, and Centro de investigación en Red en Enfermedades Neurodegenerativas (CIBERNED), Universidad Autónoma de Madrid, 28029 Madrid, Spain.
Exp Neurol. 2007 Nov;208(1):120-6. doi: 10.1016/j.expneurol.2007.07.022. Epub 2007 Aug 22.
Epidemiological studies suggest that some pesticides might constitute a risk factor for Parkinson's disease (PD). However, risk assessment cannot be performed in the current experimental animal models because they use non-natural pathways of pesticide exposure, such as intraperitoneal or intravenous injection, that might bypass body defences. A new model based on daily inoculation of neurotoxins in the nasal cavity of C57BL/6 mice for 30 days was used to evaluate risk of three complex I inhibitors, 1-methyl-4-phenyl1,2,3,6-tetrahydropyridine (MPTP), rotenone and paraquat. These compounds displayed very different effects on motor activity, striatal dopamine and dihydroxyphenylacetic acid (DOPAC) levels and loss of dopaminergic neurons. MPTP-treated mice developed motor deficits that correlated with a severe depletion of striatal dopamine levels, and loss of tyrosine hydroxylase staining in substantia nigra and striatum. By contrast, rotenone-treated mice or rats were asymptomatic. Paraquat induced severe hypokinesia and vestibular damage but did not alter the nigrostriatal system. The new animal model described here, based on chronic intranasal inoculation of neurotoxicants, provides a new tool to assess the potential danger of environmental toxins as risk factors for development of PD.
流行病学研究表明，某些农药可能是帕金森病（PD）的一个风险因素。然而，目前的实验动物模型无法进行风险评估，因为它们采用的是农药暴露的非自然途径，如腹腔注射或静脉注射，这可能会绕过身体的防御机制。一种基于在C57BL/6小鼠鼻腔中每日接种神经毒素30天的新模型，被用于评估三种复合体I抑制剂1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）、鱼藤酮和百草枯的风险。这些化合物对运动活动、纹状体多巴胺和二羟基苯乙酸（DOPAC）水平以及多巴胺能神经元的损失表现出非常不同的影响。MPTP处理的小鼠出现了运动缺陷，这与纹状体多巴胺水平的严重耗竭以及黑质和纹状体中酪氨酸羟化酶染色的丧失相关。相比之下，鱼藤酮处理的小鼠或大鼠没有症状。百草枯导致严重的运动减退和前庭损伤，但未改变黑质纹状体系统。这里描述的基于慢性鼻腔接种神经毒物的新动物模型，为评估环境毒素作为PD发病风险因素的潜在危险提供了一种新工具。
