Tumor necrosis factor α is toxic to embryonic mesencephalic dopamine neurons
Tumor necrosis factor α is toxic to embryonic mesencephalic dopamine neurons
复制标题
DOI：
10.1006/exnr.2001.7688
复制
发表时间：
2001-06-01
影响因子：
5.3
通讯作者：
Carvey, PM
中科院分区：
文献类型：
--
作者：
McGuire, SO;Ling, ZD;Carvey, PM
帕金森病 (PD) 患者死后大脑和脑脊液中促炎细胞因子肿瘤坏死因子 α (TNF α) 的水平升高。这一观察结果为 TNF α 与神经变性的关联提供了基础，但多巴胺 (DA) 神经元的特定毒性尚未确定。因此，我们利用胚胎大鼠中脑的原代培养物研究了 TNF α 诱导的 DA 神经元毒性。暴露于 TNF α 会导致 DA 神经元呈剂量依赖性减少，酪氨酸羟化酶免疫反应 (THir) 细胞数量减少就证明了这一点。 TNF α 毒性对 DA 神经元具有选择性，因为神经胶质细胞计数和神经元总数均未减少，并且乳酸脱氢酶测定未证明一般细胞毒性。许多对 TH 保持免疫反应的细胞已经萎缩并变圆，且细胞突起破碎、钝化或缺失。然而，TNFα处理的培养物还含有一些THir细胞，这些细胞似乎未受损并且可能对TNFα诱导的毒性具有抵抗力。此外，免疫细胞化学显示中脑培养物内的所有细胞上都有一定程度的 TNF α 受体 1 (p55，R1) 和 TNF α 受体 2 (p75，R2) 的基础表达，即使只有 DA 神经元受到 TNF α 治疗的影响。这些数据强烈表明 TNF α 介导敏感 DA 神经元群体中的细胞死亡，并支持促炎细胞因子可能参与 PD 中 DA 神经元的变性。 (C) 2001 年学术出版社。
Levels of the proinflammatory cytokine tumor necrosis factor alpha (TNF alpha) are increased in postmortem brain and cerebral spinal fluid from patients with Parkinson's disease (PD), This observation provides a basis for associating TNF alpha with neurodegeneration, but a specific toxicity in dopamine (DA) neurons has not been firmly established. Therefore, we investigated TNF alpha -induced toxicity in DA neurons by utilizing primary cultures of embryonic rat mesencephalon. Exposure to TNF alpha resulted in a dose-dependent decrease in DA neurons as evidenced by decreased numbers of tyrosine hydroxylase-immunoreactive (THir) cells. TNF alpha toxicity was selective for DA neurons in that neither glial cell counts nor the total number of neurons was decreased and no general cytotoxicity was evidenced by lactate dehydrogenase assay. Many of the cells which remained immunoreactive for TH had shrunken and rounded cell bodies with broken, blunted, or absent processes. However, TNF alpha -treated cultures also contained some THir cells which appeared to be undamaged and possibly resistant to TNF alpha -induced toxicity. Additionally, immunocytochemistry revealed basal expression of TNF alpha receptor 1 (p55, R1) and TNF alpha receptor 2 (p75, R2) on all cells within the mesencephalic cultures to some degree, even though only DA neurons were affected by TNF alpha treatment. These data strongly suggest that TNF alpha mediates cell death in a sensitive population of DA neurons and support the potential involvement of proinflammatory cytokines in the degeneration of DA neurons in PD. (C) 2001 Academic Press.