Neuroprotective effect of CPDT on THA-induced cortical motor neuron death in an organotypic culture model
Neuroprotective effect of CPDT on THA-induced cortical motor neuron death in an organotypic culture model
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CPDT 对器官培养模型中 THA 诱导的皮质运动神经元死亡的神经保护作用
DOI：
10.1016/j.brainresbull.2010.09.001
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发表时间：
2010-11-20
影响因子：
3.8
通讯作者：
Ren, Wen-Bo
中科院分区：
文献类型：
--
作者：
Liu, Xiao-Yun;Li, Chun-Yan;Ren, Wen-Bo
脑卒中创伤和运动神经元疾病会导致大脑皮层运动神经元谷氨酸(复合材料)死亡或损伤会引发运动神经元损伤急性运动神经元损失和慢性运动神经元变性有必要找到有效的策略来保护复合材料会引起各种病理条件5 6-Dihydrocyclopenta-1 2-dithiole-3-thione (CPDT)是一种二期酶诱导在我们以前的报告CPDT被显示通过激活Nrf2/ARE通路增加抗氧化能力对脊髓的神经保护作用，本研究旨在了解CPDT是否可以预防CMN细胞tha诱导的死亡。我们建立了一个器官型脑切片培养系统，在培养基中加入谷氨酸转运抑制剂tho -hydroxyaspartate (THA)，以谷氨酸兴奋性毒性诱导CMN死亡。脑切片用CPDT预处理48 h， CPDT和THA同时处理3周，我们发现CPDT预处理显著提高CMN存活率，THA处理后培养基中谷氨酸浓度显著升高，而无显著降低然而，CPDT预处理组Nrf2和HO-1蛋白表达均显著升高，CPDT刺激后Nrf2蛋白易位至细胞核。这些研究结果表明，CPDT可以通过激活Nrf2通路和增加HO-1蛋白表达来保护CMNs免受tha诱导的运动神经元死亡。因此，增加抗氧化防御能力应有利于谷氨酸excitotoxic insult (C) 2010 Elsevier Inc .版权所有
Brain stroke trauma and motor neuron disease each can result in cortical motoneuron (CMN) death or impairment Glutamate excitotoxicity Induces motor neuron damage in both acute motor neuron loss and chronic motor neuron degeneration It is necessary to find effective strategies to protect CMNs from excitotoxicity in a variety of pathological conditions 5 6-Dihydrocyclopenta-1 2-dithiole-3-thione (CPDT) is one of the phase II enzyme inducers In our previous report CPDT was shown to have neuroprotective effects on the spinal cord by activating the Nrf2/ARE pathway to increase antioxidative capacity In this study in order to figure out whether CPDT can prevent CMN s from THA-Induced death, we set up an organotypic brain slice culture system Threo-hydroxyaspartate (THA) a glutamate transport inhibitor was added to the culture medium to induce CMN death by glutamate excitotoxicity Brain slices were pretreated with CPDT for 48 h then treated with CPDT and THA simultaneously for 3 weeks We found that pretreatment with CPDT significantly increased CMN survival Glutamate concentration in the culture medium was significantly greater following THA treatment whereas no significant decrease was found in the CPDT pretreatment group However both Nrf2 and HO-1 protein expression was significantly elevated in the CPDT pretreatment group and Nrf2 protein translocated to the nucleus after CPDT stimulation These findings suggest that CPDT can protect CMNs from THA-Induced motor neuron death by activating the Nrf2 pathway and increasing HO-1 protein expression Therefore increasing antioxidative defense capacity should benefit to upper motor neuron survival following a glutamate excitotoxicity insult (C) 2010 Elsevier Inc All rights reserved