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L-DOPA 治疗可逆转锰暴露诱导的帕金森病实验模型中的运动改变。

L-DOPA treatment reverses the motor alterations induced by manganese exposure as a Parkinson disease experimental model.

机构信息

Laboratorio de Neuromorfologia, FES Iztacala, UNAM, Av. de los Barrios 1, Tlalnepantla 54090, Mexico.

出版信息

Neurosci Lett. 2010 Mar 3;471(2):79-82. doi: 10.1016/j.neulet.2010.01.015. Epub 2010 Jan 15.

DOI:10.1016/j.neulet.2010.01.015
PMID:20079802
Abstract

This investigation was designed to determine whether l-DOPA treatment improves the motor alterations observed after divalent and trivalent manganese (Mn) mixture inhalation on mice to ensure that the alterations are of dopaminergic origin. CD-1 male mice inhaled a mixture of 0.04 M manganese chloride (MnCl(2)) and manganese acetate (Mn(OAc)(3)), 1h 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. Overall behavior was assessed by ratings and by videotaped analyses; by the end of Mn exposure period, 10 mice were orally treated with 7.5mg/kg L-DOPA. After 5 months of Mn-mixture inhalation striatal dopamine content decreased 71%, mice developed evident deficits in motor performance manifested as akinesia, postural instability and action tremor; these alterations were reverted with L-DOPA treatment. Our results suggest that the motor alterations induced by the inhalation of the combination of MnCl(2)/Mn(OAc)(3) are related to nigrostriatal dopaminergic function providing new light on the understanding of manganese neurotoxicity as a suitable Parkinson disease experimental model.

摘要

本研究旨在确定 l-DOPA 治疗是否能改善二价和三价锰(Mn)混合物吸入后小鼠观察到的运动改变,以确保这些改变是多巴胺能起源的。CD-1 雄性小鼠吸入 0.04 M 氯化锰(MnCl(2))和醋酸锰(Mn(OAc)(3))混合物,1h 两次,每周一次,共 5 个月。在 Mn 暴露之前,动物接受运动功能测试训练,并在暴露后每周进行评估。整体行为通过评分和录像分析进行评估;在 Mn 暴露期结束时,10 只小鼠口服 7.5mg/kg L-DOPA。吸入 Mn 混合物 5 个月后,纹状体多巴胺含量下降 71%,小鼠出现明显的运动功能障碍,表现为运动迟缓、姿势不稳和动作震颤;这些改变可通过 L-DOPA 治疗逆转。我们的结果表明,吸入 MnCl(2)/Mn(OAc)(3)混合物引起的运动改变与黑质纹状体多巴胺能功能有关,为理解锰神经毒性作为一种合适的帕金森病实验模型提供了新的思路。

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