GDNF and NT-4 protect midbrain dopaminergic neurons from toxic damage by iron and nitric oxide
GDNF and NT-4 protect midbrain dopaminergic neurons from toxic damage by iron and nitric oxide
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DOI：
10.1006/exnr.2000.7339
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发表时间：
2000-05-01
影响因子：
5.3
通讯作者：
Krieglstein, K
中科院分区：
文献类型：
--
作者：
Lingor, P;Unsicker, K;Krieglstein, K
自由基的形成被认为是导致帕金森病（PD）的黑质多巴胺能（DAergic）细胞死亡的主要原因。在这项研究中，我们使用了包括铁和硝普钠在内的几种自由基供体来诱导从胚胎大鼠脑底培养的能神经元的毒性作用。通过乳酸脱氢酶（LDH）测定细胞总体存活率，通过酪氨酸羟化酶阳性细胞计数监测神经元存活率。我们的数据表明，中脑神经元群对自由基介导的损伤的易感性是中脑神经元总数的四倍。神经营养因子GDNF和NT-4的应用，能神经元具有特异性受体，在毒素给药之前保护这些神经元免受毒素介导的死亡，而毒素介导的死亡全部或部分发生在细胞凋亡的迹象下。这些发现强调了GDNF和NT-4在设计未来PD治疗概念中的重要性。(C) 2000年学术出版社。
Free radical formation is considered to be a major cause of dopaminergic (DAergic) cell death in the substantia nigra leading to Parkinson's disease (PD). In this study we employed several radical donors including iron and sodium nitroprusside to induce toxic effects on DAergic neurons cultured from the embryonic rat midbrain floor. Overall cell survival was assessed by assaying LDH, and DAergic neuron survival was monitored by counting tyrosine hydroxylase-positive cells. Our data suggest that the DAergic neuron population is about fourfold more susceptible to free-radical-mediated damage than the total population of midbrain neurons. Application of the neurotrophic factors GDNF and NT-4, for which DAergic neurons have specific receptors, prior to toxin administration protected these neurons from toxin-mediated death, which, fully or in part, occurs under the signs of apoptosis. These findings underscore the importance of GDNF and NT-4 in designing future therapeutical concepts for PD. (C) 2000 Academic Press.