Progressive degeneration of dopamine neurons in 6-hydroxydopamine rat model of Parkinson's disease does not involve activation of caspase-9 and caspase-3
Progressive degeneration of dopamine neurons in 6-hydroxydopamine rat model of Parkinson's disease does not involve activation of caspase-9 and caspase-3
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DOI：
10.1002/jnr.21480
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发表时间：
2008-02-01
影响因子：
4.2
通讯作者：
Bohn, Martha C.
中科院分区：
文献类型：
--
作者：
Ebert, Allison D.;Hann, Hoo Jae;Bohn, Martha C.
6-羟基多巴胺 (6-OHDA) 是一种导致多巴胺 (DA) 神经元死亡的神经毒素，通常用于制作啮齿类动物帕金森病 (PD) 的实验模型。在 Sauer 和 Oertel 首次描述的 PD 大鼠模型中，纹状体注射 6-OHDA 后的几周内，DA 神经元逐渐死亡。一般认为，DA 神经元在暴露于 6-OHDA 后会通过细胞凋亡而死亡，但缺乏支持 caspase 酶级联激活的数据。在这项研究中，我们试图确定参与内在凋亡级联的半胱天冬酶是否在 6-OHDA 诱导的 PD 大鼠渐进性损伤模型中的 DA 神经元死亡的初始阶段发挥作用。我们发现，在成年大鼠纹状体中注射 6-OHDA 不会激活 caspase-9 或 caspase-3，也不会增加病变后直至 7 天的不同存活时间黑质中 caspase 依赖性裂解产物的水平，尽管这种范例产生了 DA 神经元损失。这些数据表明，在成年大鼠大脑中，其末端受到 6-OHDA 攻击的 DA 神经元不会通过经典的 caspase 依赖性细胞凋亡机制而死亡。 (C) 2007 Wiley-Liss, Inc.
6-Hydroxydopamine (6-OHDA), a neurotoxin that causes the death of dopamine (DA) neurons, is commonly used to produce experimental models of Parkinson's disease (PD) in rodents. In the rat model of PD first described by Sauer and Oertel, DA neurons progressively die over several weeks following a striatal injection of 6-OHDA. It is generally assumed that DA neurons die through apoptosis after exposure to 6-OHDA, but data supporting activation of a caspase enzymatic cascade are lacking. In this study, we sought to determine if caspases involved in the intrinsic apoptotic cascade play a role in the initial stages of 6-OHDA-induced death of DA neurons in the progressively lesioned rat model of PD. We found that injection of 6-OHDA into adult rat striatum did not activate caspase-9 or caspase-3 or increase levels of caspase-dependent cleavage products in the substantia nigra at various survival times up to 7 days after the lesion, even though this paradigm produced DA neuronal loss. These data suggest that in the adult rat brain DA neurons whose terminals are challenged with 6-OHDA do not die through a classical caspase-dependent apoptotic mechanism. (C) 2007 Wiley-Liss, Inc.