Neuromorphology Lab, Facultad de Estudios Superiores Iztacala, UNAM, Av. de los Barrios 1, Los Reyes Iztacala, Tlalnepantla, Edo. Mex. 54090, Mexico.
Neurotoxicology. 2012 Oct;33(5):1346-55. doi: 10.1016/j.neuro.2012.08.012. Epub 2012 Sep 4.
Manganese (Mn) is an essential trace metal. Regardless of its essentiality, it has been reported that the overexposure causes neurotoxicity manifested as extrapyramidal symptoms similar to those observed in Parkinson disease (PD). Recently, our group reported that mice that inhaled for 5 months the mixture of manganese chloride (MnCl(2)) and manganese acetate Mn(OAc)(3) developed movement abnormalities, significant loss of substantia nigra compacta (SNc) dopaminergic neurons, dopamine depletion and improved behavior with l-DOPA treatment. However, this model has only been characterized in mice. In order to have a well-supported and generalizable model in rodents, we used male Wistar rats that inhaled a mixture of 0.04 M MnCl(2) and 0.02 M Mn(OAc)(3), 1h three times a week for 6 months. Before Mn exposure, animals were trained to perform motor tests (Beam-walking and Single-pellet reaching tasks) and were evaluated each week after the exposure. The mixture of MnCl(2)/Mn(OAc)(3) caused alterations in the motor tests, 75.95% loss of SNc dopaminergic neurons, and no cell alterations in Globus Pallidus or striatum. With these results we conclude that the inhalation of the mixture of Mn compounds is a useful model in rodents for the study of PD.
锰（Mn）是一种必需的微量元素。尽管它是必需的，但据报道，过量暴露会导致神经毒性，表现为类似于帕金森病（PD）中观察到的锥体外系症状。最近，我们的研究小组报告称，吸入锰氯化物（MnCl2）和醋酸锰（Mn（OAc）3）混合物 5 个月的小鼠出现运动异常、显著丧失黑质致密部（SNc）多巴胺能神经元、多巴胺耗竭，并在用 l-DOPA 治疗后改善了行为。然而，这种模型仅在小鼠中进行了表征。为了在啮齿动物中有一个得到充分支持和可推广的模型，我们使用雄性 Wistar 大鼠，每周三次吸入 0.04 M MnCl2 和 0.02 M Mn（OAc）3 的混合物，每次 1 小时，持续 6 个月。在 Mn 暴露之前，动物接受了运动测试（走平衡木和单颗粒伸出任务）的训练，并在暴露后的每周进行评估。MnCl2/Mn（OAc）3 的混合物导致运动测试发生改变，SNc 多巴胺能神经元丧失 75.95%，而苍白球或纹状体没有细胞改变。有了这些结果，我们得出结论，吸入 Mn 化合物混合物是研究 PD 的啮齿动物模型的有用方法。
