期刊
BRAIN RESEARCH BULLETIN
卷 83, 期 6, 页码 345-350出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.brainresbull.2010.09.001
关键词
Cortical motoneuron (CMN); Threo-hydroxyaspartate (THA); 5 6-Dihydrocyclopenta-1 2-dithiole-3-thione; (CPDT); NF-E2-related factor (Nrf2); Heme oxygenase-1 (HO-1)
资金
- Natural Science Foundation of China [30670732, 30700254]
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
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