Traumatic brain injury and the effects of diazepam, diltiazem, and MK-801 on GABA-A receptor subunit expression in rat hippocampus.
Traumatic brain injury and the effects of diazepam, diltiazem, and MK-801 on GABA-A receptor subunit expression in rat hippocampus.
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DOI：
10.1186/1423-0127-17-38
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发表时间：
2010-05-18
影响因子：
11
通讯作者：
Hamm RJ
中科院分区：
文献类型：
--
作者：
Gibson CJ;Meyer RC;Hamm RJ
创伤性脑损伤(TBI)后兴奋性氨基酸的释放和随后的生化级联反应已经被很好地记录下来，特别是谷氨酸相关的兴奋性毒性。然而，脑损伤对抑制性GABA-A受体的基本功能的影响却知之甚少。采用免疫印迹法检测脑损伤后3h、6h、2 4h和7d大鼠海马区GABAA受体亚基α1、α2、α3、α5、β3和γ2蛋白表达的变化。损伤前注射MK-801阻断N-甲基-D-天门冬氨酸受体的钙内流，地尔硫卓阻断L电压门控性钙内流，或安定增强氯离子电导，并重新检测α1、α2、α3和γ2的蛋白表达，在第一项研究中，这些蛋白都是苯二氮卓类敏感的GABA-A受体的重要成分。Western印迹分析显示，在损伤后的任何时间点，GABAA受体α2或α5亚单位的蛋白表达没有受到损伤的影响。α-1、α-3、β-3和γ-2蛋白表达随时间变化显著。地尔硫卓和安定治疗后GABA-A亚基的变化模式几乎相同，而MK-801在脑损伤后24小时所有亚基的正常表达。这些研究首次证明了在体脑损伤后GABA-A受体亚单位的表达发生了改变，这种改变可能是由海马神经元中钙离子介导的级联反应所驱动的。脑创伤后海马区GABA-A受体的变化可能会产生深远的影响，因为它们在维持抑制性平衡方面具有重要意义，而且对神经元功能有广泛的影响。
Excitatory amino acid release and subsequent biochemical cascades following traumatic brain injury (TBI) have been well documented, especially glutamate-related excitotoxicity. The effects of TBI on the essential functions of inhibitory GABA-A receptors, however, are poorly understood. We used Western blot procedures to test whether in vivo TBI in rat altered the protein expression of hippocampal GABA-A receptor subunits α1, α2, α3, α5, β3, and γ2 at 3 h, 6 h, 24 h, and 7 days post-injuy. We then used pre-injury injections of MK-801 to block calcium influx through the NMDA receptor, diltiazem to block L-type voltage-gated calcium influx, or diazepam to enhance chloride conductance, and re-examined the protein expressions of α1, α2, α3, and γ2, all of which were altered by TBI in the first study and all of which are important constituents in benzodiazepine-sensitive GABA-A receptors. Western blot analysis revealed no injury-induced alterations in protein expression for GABA-A receptor α2 or α5 subunits at any time point post-injury. Significant time-dependent changes in α1, α3, β3, and γ2 protein expression. The pattern of alterations to GABA-A subunits was nearly identical after diltiazem and diazepam treatment, and MK-801 normalized expression of all subunits 24 hours post-TBI. These studies are the first to demonstrate that GABA-A receptor subunit expression is altered by TBI in vivo, and these alterations may be driven by calcium-mediated cascades in hippocampal neurons. Changes in GABA-A receptors in the hippocampus after TBI may have far-reaching consequences considering their essential importance in maintaining inhibitory balance and their extensive impact on neuronal function.
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影响因子：
3.3
作者：
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通讯作者：
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