Altered striatal dopamine release following a sub-acute exposure to manganese
Altered striatal dopamine release following a sub-acute exposure to manganese
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DOI：
10.1016/j.jneumeth.2011.06.019
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发表时间：
2011-11-15
影响因子：
3
通讯作者：
Mathews, Tiffany A.
中科院分区：
文献类型：
--
作者：
Khalid, Madiha;Aoun, Rabab A.;Mathews, Tiffany A.
某些金属是在痕量水平上调节生物功能所必需的，当过量时，可能会产生神经毒性。具体地说，长期接触高水平的锰会导致锰中毒，这是一种神经障碍，表现出类似帕金森氏症的运动和学习障碍。由于帕金森氏病的症状主要归因于纹状体中的多巴胺神经变性，因此多巴胺系统功能障碍与锰中毒的发生有关。本研究观察了C57B1/6小鼠连续皮下注射氯化锰(50 mg/kg)后第1、7、21天背侧纹状体多巴胺系统功能的变化。组织含量分析证实，在停止治疗后21天，纹状体中存在持续的锰积聚。体外快速扫描循环伏安法检测了亚急性锰对电刺激纹状体多巴胺释放和摄取的影响。虽然没有观察到锰处理后摄取率的差异，但与对照水平相比，第7天和第21天的多巴胺释放有所减弱。零净通量微透析法测定的细胞外多巴胺的基础水平在治疗后7天显著降低。另一方面，钾刺激的细胞外多巴胺的增加在所有三个时间点都被减弱。综上所述，这些发现表明，反复接触锰对纹状体多巴胺的胞吐释放有长期的调节作用，这可能参与了锰中毒的机制。(C)2011爱思唯尔B.V.保留所有权利。
Certain metals that are necessary for regulating biological function at trace levels hold the potential to become neurotoxic when in excess. Specifically, chronic exposure to high levels of manganese leads to manganism, a neurological disorder that exhibits both motor and learning deficits similar to Parkinson's disease. Since Parkinson's disease symptomatology is primarily attributed to dopamine neurodegeneration in the striatum, dopamine system dysfunction has been implicated in the onset of manganism. In this study, dopamine system function in the dorsal striatum was evaluated in C57B1/6 mice, 1, 7, and 21 days following repeated injections of manganese(II)chloride (50 mg/kg, subcutaneous) intermittently for 7 days. Tissue content analysis confirmed the presence of persistent accumulation of manganese in the striatum up to 21 days after cessation of treatment. In vitro fast scan cyclic voltammetry examined the effect of sub-acute manganese on electrically stimulated dopamine release and uptake in the striatum. While no difference was observed in uptake rates following manganese treatment, dopamine release was attenuated on days 7 and 21, compared to control levels. Basal levels of extracellular dopamine determined by the zero net flux microdialysis method were significantly lower in manganese-treated mice at 7 days post-treatment. On the other hand, potassium stimulated increases in extracellular dopamine were attenuated at all three time points. Together, these findings indicate that repeated manganese exposure has long-term effects on the regulation of exocytotic dopamine release in the striatum, which may be involved in the mechanism underlying manganese toxicity. (C) 2011 Elsevier B.V. All rights reserved.