Ordoñez-Librado J L, Gutierrez-Valdez A L, Colín-Barenque L, Anaya-Martínez V, Díaz-Bech P, Avila-Costa M R
Laboratorio de Neuromorfologia, Facultad de Estudios Superiores Iztacala, UNAM, Los Reyes Iztacala, Tlalnepantla, Edo Mex, Mexico.
Neuroscience. 2008 Jul 31;155(1):7-16. doi: 10.1016/j.neuroscience.2008.05.012. Epub 2008 May 21.
The present study investigates the effects of divalent and trivalent manganese (Mn(2+)/Mn(3+)) mixture inhalation on mice to obtain a novel animal model of Parkinson disease (PD) inducing bilateral and progressive cell death in the substantia nigra compacta (SNc) and correlating these alterations with motor disturbances. CD-1 male mice inhaled a mixture of 0.04 M manganese chloride (MnCl(2)) and manganese acetate (Mn(OAc)(3)), 1 h twice a week for 5 months. Before Mn exposure, animals were trained to perform motor function tests and were evaluated each week after the exposure. By doing this, overall behavior was assessed by ratings and by videotaped analyses; by the end of Mn exposure period, animals were killed. The mesencephalon was processed for tyrosine hydroxylase (TH) immunocytochemistry. After 5 months of Mn mixture inhalation, mice developed evident deficits in their motor performance manifested as akinesia, postural instability and action tremor. SNc of the Mn-exposed animals showed an important decrease (67.58%) in the number of TH-immunopositive neurons. Our data provide evidence that MnCl(2) and Mn(OAc)(3) mixture inhalation produces similar morphological and behavioral alterations to those observed in PD providing a useful experimental model for the study of this neurodegenerative disease.
本研究调查了吸入二价和三价锰（Mn(2+)/Mn(3+)）混合物对小鼠的影响，以获得一种新型帕金森病（PD）动物模型，该模型可诱导黑质致密部（SNc）出现双侧性和进行性细胞死亡，并将这些改变与运动障碍相关联。CD-1雄性小鼠吸入0.04 M氯化锰（MnCl(2)）和醋酸锰（Mn(OAc)(3)）的混合物，每周两次，每次1小时，持续5个月。在锰暴露前，对动物进行运动功能测试训练，并在暴露后每周进行评估。通过这种方式，通过评分和录像分析评估总体行为；在锰暴露期结束时，处死动物。对中脑进行酪氨酸羟化酶（TH）免疫细胞化学处理。吸入锰混合物5个月后，小鼠出现明显的运动功能缺陷，表现为运动不能、姿势不稳和动作性震颤。锰暴露动物的SNc中TH免疫阳性神经元数量显著减少（67.58%）。我们的数据表明，吸入MnCl(2)和Mn(OAc)(3)混合物会产生与PD中观察到的类似的形态和行为改变，为研究这种神经退行性疾病提供了一个有用的实验模型。
