Manganese exposure is cytotoxic and alters dopaminergic and GABAergic neurons within the basal ganglia.
Manganese exposure is cytotoxic and alters dopaminergic and GABAergic neurons within the basal ganglia.
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DOI：
10.1111/j.1471-4159.2009.06145.x
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发表时间：
2009-07
影响因子：
4.7
通讯作者：
McLaughlin B
中科院分区：
文献类型：
--
作者：
Stanwood GD;Leitch DB;Savchenko V;Wu J;Fitsanakis VA;Anderson DJ;Stankowski JN;Aschner M;McLaughlin B
锰是一种必需的营养素，是氨基酸、蛋白质和脂质正常代谢的组成部分。过量的环境暴露于锰可产生类似于帕金森病（PD）中观察到的锥体外系症状。我们使用体内和体外模型来研究锰暴露引起的细胞和电路改变。用10-00µM氯化锰（MnCl 2）处理原代中脑培养物，即使在亚毒性浓度下，也会导致神经元细胞骨架发生显著变化。使用红色荧光蛋白（RFP）的酪氨酸羟化酶（TH）启动子驱动的小鼠培养物，我们发现多巴胺能神经元更容易受到锰毒性。为了了解多巴胺能细胞对慢性锰暴露的脆弱性，给小鼠IP注射MnCl 2 30天。我们观察到20%的减少TH-阳性神经元在黑质pars延髓（SNPC）锰治疗后。尼氏小体的定量显示SNpc细胞数量普遍减少。基底神经节的其他区域也被锰改变，如纹状体中GAD 67的损失所证明的。这些研究表明，急性锰暴露诱导细胞骨架功能障碍之前，变性和慢性锰暴露导致神经化学功能障碍与重叠功能的PD。
Manganese is an essential nutrient, integral to proper metabolism of amino acids, proteins and lipids. Excessive environmental exposure to manganese can produce extrapyramidal symptoms similar to those observed in Parkinson’s disease (PD). We used in vivo and in vitro models to examine cellular and circuitry alterations induced by manganese exposure. Primary mesencephalic cultures were treated with 10–00µM manganese chloride (MnCl2) which resulted in dramatic changes in the neuronal cytoskeleton even at subtoxic concentrations. Using cultures from mice with red fluorescent protein (RFP) driven by the tyrosine hydroxylase (TH) promoter, we found that dopaminergic neurons were more susceptible to manganese toxicity. To understand the vulnerability of dopaminergic cells to chronic manganese exposure, mice were given IP injections of MnCl2 for 30 days. We observed a 20% reduction in TH-positive neurons in the substantia nigra pars compacta (SNpc) following manganese treatment. Quantification of Nissl bodies revealed a widespread reduction in SNpc cell numbers. Other areas of the basal ganglia were also altered by manganese as evidenced by the loss of GAD67 in the striatum. These studies suggest that acute manganese exposure induces cytoskeletal dysfunction prior to degeneration and that chronic manganese exposure results in neurochemical dysfunction with overlapping features to PD.
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影响因子：
--
作者：
ABERCROMBIE, M
通讯作者：
ABERCROMBIE, M
DOI：
10.1196/annals.1306.009
发表时间：
2004-01-01
期刊：
REDOX-ACTIVE METALS IN NEUROLOGICAL DISORDERS
影响因子：
--
作者：
Dobson, AW;Erikson, KM;Aschner, M
通讯作者：
Aschner, M
影响因子：
2.1
作者：
Dorman, DC;McManus, BE;Everitt, JI
通讯作者：
Everitt, JI
影响因子：
3.5
作者：
Cappelletti, G;Surrey, T;Maci, R
通讯作者：
Maci, R
影响因子：
3.4
作者：
Erikson, K;Aschner, M
通讯作者：
Aschner, M