Kim Hyung-Wook, Chang Yunyoung C, Chen Mei, Rapoport Stanley I, Rao Jagadeesh S
Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
BMC Neurosci. 2009 Sep 28;10:123. doi: 10.1186/1471-2202-10-123.
Chronic N-Methyl-d-aspartate (NMDA) administration to rats is reported to increase arachidonic acid signaling and upregulate neuroinflammatory markers in rat brain. These changes may damage brain cells. In this study, we determined if chronic NMDA administration (25 mg/kg i.p., 21 days) to rats would alter expression of pro- and anti-apoptotic factors in frontal cortex, compared with vehicle control.
Using real time RT-PCR and Western blotting, chronic NMDA administration was shown to decrease mRNA and protein levels of anti-apoptotic markers Bcl-2 and BDNF, and of their transcription factor phospho-CREB in the cortex. Expression of pro-apoptotic Bax, Bad, and 14-3-3zeta was increased, as well as Fluoro-Jade B (FJB) staining, a marker of neuronal loss.
This alteration in the balance between pro- and anti-apoptotic factors by chronic NMDA receptor activation in this animal model may contribute to neuronal loss, and further suggests that the model can be used to examine multiple processes involved in excitotoxicity.
据报道，对大鼠长期给予N-甲基-D-天冬氨酸（NMDA）会增加花生四烯酸信号传导，并上调大鼠脑中的神经炎症标志物。这些变化可能会损害脑细胞。在本研究中，我们确定与溶剂对照组相比，对大鼠长期给予NMDA（25mg/kg腹腔注射，共21天）是否会改变额叶皮质中促凋亡和抗凋亡因子的表达。
使用实时逆转录聚合酶链反应（RT-PCR）和蛋白质免疫印迹法显示，长期给予NMDA会降低皮质中抗凋亡标志物Bcl-2、脑源性神经营养因子（BDNF）及其转录因子磷酸化环磷腺苷效应元件结合蛋白（phospho-CREB）的mRNA和蛋白质水平。促凋亡蛋白Bax、Bad和14-3-3ζ的表达增加，同时神经元损失标志物氟玉B（FJB）染色也增加。
在该动物模型中，长期激活NMDA受体会改变促凋亡和抗凋亡因子之间的平衡，这可能导致神经元损失，并进一步表明该模型可用于研究兴奋性毒性涉及的多个过程。
