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急性脊髓损伤持续降低 AMPA 受体的 R/G RNA 编辑。

Acute spinal cord injury persistently reduces R/G RNA editing of AMPA receptors.

机构信息

Division of Biology and Genetics, Department of Biomedical Sciences and Biotechnologies, University of Brescia, Brescia, Italy.

出版信息

J Neurochem. 2010 Jul;114(2):397-407. doi: 10.1111/j.1471-4159.2010.06767.x. Epub 2010 Apr 23.

Abstract

Spinal cord injury (SCI) triggers a complex ischemic and inflammatory reaction, involving activation of neurotransmitter systems, in particular glutamate, culminating in cell death. We hypothesized that SCI might lead to alteration in the RNA editing of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors that govern critical determinants of neuronal survival. To this end, we examined the molecular changes set in motion by SCI that affect the channel properties of AMPA receptors. SCI strongly reduced the level of AMPA receptor R/G editing, involving not only the site of the lesion but also adjacent areas of the cord spared by the lesion. The effects, with changes for some subunits and loci, were observed as long as 30 days after lesioning and may correlate with a partial decrease in enzymatic activity of adenosine deaminase acting on RNA 2 (ADAR2), as deduced from the analysis of ADAR2 self-editing. The reduced editing at the R/G site of glutamate receptor subunits (GluRs) is likely to reduce post-synaptic excitatory responses to glutamate, thus limiting the progression of cell death; however, prolonged suppression of GluR function in later stages may hinder synaptic plasticity. These observations provide the first direct evidence of the potential contribution of RNA editing to excitatory neural injury and recovery after SCI.

摘要

脊髓损伤 (SCI) 会引发复杂的缺血和炎症反应,涉及神经递质系统的激活,特别是谷氨酸,最终导致细胞死亡。我们假设 SCI 可能导致调节神经元存活的关键决定因素的 AMPA 受体的 RNA 编辑发生改变。为此,我们研究了 SCI 引发的改变,这些改变会影响 AMPA 受体的通道特性。SCI 强烈降低了 AMPA 受体 R/G 编辑的水平,不仅涉及病变部位,还涉及病变部位周围的脊髓区域。这些影响,对于一些亚基和基因座而言,在损伤后长达 30 天内都能观察到,并且可能与腺苷脱氨酶作用于 RNA 2 (ADAR2) 的酶活性部分降低相关,这可以从 ADAR2 自我编辑的分析中推断出来。谷氨酸受体亚基 (GluR) 的 R/G 位点编辑减少很可能会降低谷氨酸的突触后兴奋性反应,从而限制细胞死亡的进展;然而,在后期长时间抑制 GluR 功能可能会阻碍突触可塑性。这些观察结果为 RNA 编辑对 SCI 后兴奋性神经损伤和恢复的潜在贡献提供了第一个直接证据。

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