Intra-parenchymal injection of tumor necrosis factor-α and interleukin 1-β produces dopamine neuron loss in the rat
Intra-parenchymal injection of tumor necrosis factor-α and interleukin 1-β produces dopamine neuron loss in the rat
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DOI：
10.1007/s00702-004-0222-z
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发表时间：
2005-05-01
影响因子：
3.3
通讯作者：
Ling, ZD
中科院分区：
文献类型：
--
作者：
Carvey, PM;Chen, EY;Ling, ZD
炎症过程被认为是帕金森氏病(PD)患者多巴胺(DA)神经元丢失的基础。然而，目前还不清楚炎症是在这种损失之前发生的，还是它的结果。我们将肿瘤坏死因子α(TNFα)和白介素1β(IL-1β)注射到正中前脑束，以确定这些促炎细胞因子是否可以单独诱导黑质(SN)中DA神经元的丢失。DA细胞丢失的幅度和纹状体DA的减少，都与剂量和牺牲时间有关。与单独注射细胞因子相比，同时注射两种细胞因子会产生更大的细胞损失和DA减少。DA神经元的丢失在黑质外侧及其腹侧层更为明显，与注射其他毒素时相似。这些结果表明，肿瘤坏死因子α和白介素1β可以单独诱导DA神经元的丢失，并且可以独立于其他炎症事件而导致DA神经元的丢失。
Inflammatory processes are thought to underlie the dopamine (DA) neuron loss seen in Parkinson's disease (PD). However, it is not known if the inflammation precedes that loss, or is a consequence of it. We injected tumor necrosis factor alpha (TNF alpha) and interleukin 1 beta (IL-1 beta) into the median forebrain bundle to determine if these pro-inflammatory cytokines could induce DA neuron loss in the substantia nigra (SN) by themselves. The magnitude of the DA cell loss as well as the decreases in striatal DA, were both dose and time to sacrifice dependent. Injecting both cytokines together produced greater cell losses and DA reductions than that seen when the cytokines were injected alone. The DA neuron loss seen was more pronounced in the lateral nigra and its ventral tier and similar to that seen when other toxins are injected. These data suggest that TNF alpha and IL-1 beta can induce DA neuron loss by themselves and could produce DA neuron loss independent of other inflammatory events.