Defazio G, Soleo L, Zefferino R, Livrea P
Institute of Neurology, University of Bari, Italy.
Brain Res Bull. 1996;40(4):257-62. doi: 10.1016/0361-9230(96)00041-x.
Exposure to elevated levels of Manganese (Mn) can result in an irreversible brain disease characterized by extrapyramidal signs and symptoms resembling Parkinson's disease. To identify the neuronal target of Mn neurotoxicity, MnCl2 was added to serumless dissociated mesencephalic-striatal cultures from rat embryo on day 4 in vitro. High affinity 3H-dopamine (DA) and 14C-GABA uptakes were assessed as specific functional markers of DAergic and GABAergic cell viability, respectively. After 60-min exposure, MnCl2 at 0-200 microM did not modify the morphologic appearance of the cultures, specific DA and GABA uptakes, or the number of DA neurons visualized by immuno-cytochemical staining with tyrosine hydroxylase. In contrast, culture exposure to 20 microM MnCl2 for 24 h selectively reduced specific GABA uptake without affecting specific DA uptake or the number of DA neurons. The exposure to a higher MnCl2 concentration was accompanied by signs of general toxicity. Striatal GABA neurons seemed to be more susceptible to Mn toxicity than mesencephalic GABA neurons. Overall, our data suggest that striatal neurons rather than mesencephalic DA neurons may be the main target of Mn neurotoxicity.
暴露于高水平的锰（Mn）会导致一种不可逆的脑部疾病，其特征为锥体外系体征和症状，类似于帕金森病。为了确定锰神经毒性的神经元靶点，在体外培养的第4天，将氯化锰添加到来自大鼠胚胎的无血清解离中脑-纹状体培养物中。分别将高亲和力的3H-多巴胺（DA）和14C-γ-氨基丁酸（GABA）摄取评估为多巴胺能和γ-氨基丁酸能细胞活力的特异性功能标志物。暴露60分钟后，0-200微摩尔的氯化锰未改变培养物的形态外观、特异性多巴胺和γ-氨基丁酸摄取，或通过酪氨酸羟化酶免疫细胞化学染色可视化的多巴胺能神经元数量。相比之下，将培养物暴露于20微摩尔的氯化锰24小时会选择性地降低特异性γ-氨基丁酸摄取，而不影响特异性多巴胺摄取或多巴胺能神经元数量。暴露于更高浓度的氯化锰会伴有一般毒性的迹象。纹状体γ-氨基丁酸能神经元似乎比中脑γ-氨基丁酸能神经元对锰毒性更敏感。总体而言，我们的数据表明，纹状体神经元而非中脑多巴胺能神经元可能是锰神经毒性的主要靶点。
