Human spinal motoneurons express low relative abundance of GluR2 mRNA: an implication for excitotoxicity in ALS
Human spinal motoneurons express low relative abundance of GluR2 mRNA: an implication for excitotoxicity in ALS
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DOI：
10.1046/j.1471-4159.2003.01703.x
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发表时间：
2003-05-01
影响因子：
4.7
通讯作者：
Kanazawa, I
中科院分区：
文献类型：
--
作者：
Kawahara, Y;Kwak, S;Kanazawa, I
AMPA受体介导的神经毒性是目前肌萎缩侧索硬化症（ALS）病因学最合理的假设。引发这种类型的神经元死亡的机制被认为是通过AMPA受体的过度Ca 2+内流，这是由组装体中谷氨酸受体亚基2（GluR 2）的存在或不存在决定的。我们提供了第一个定量测量AMPA受体亚基mRNA的表达谱在人类单个神经元的定量RT-PCR与激光显微解剖仪。在AMPA亚基中，GluR 2在所检查的神经元亚群和组织中占绝大多数。此外，运动神经元中GluR 2 mRNA的表达水平和比例均为所有神经元亚群中最低，而ALS运动神经元中的表达水平和比例与对照组无差异，这意味着选择性减少GluR 2亚基不能成为ALS中AMPA受体介导的神经毒性的机制。然而，低相对丰度的GluR 2可能提供脊髓运动神经元的条件，很容易受到AMPA受体特性的变化，包括缺乏GluR 2 mRNA编辑ALS。
AMPA receptor-mediated neurotoxicity is currently the most plausible hypothesis for the etiology of amyotrophic lateral sclerosis (ALS). The mechanism initiating this type of neuronal death is believed to be exaggerated Ca2+-influx through AMPA receptors, which is critically determined by the presence or absence of the glutamate receptor subunit 2 (GluR2) in the assembly. We have provided the first quantitative measurements of the expression profile of AMPA receptor subunits mRNAs in human single neurons by means of quantitative RT-PCR with a laser microdissector. Among the AMPA subunits, GluR2 shared the vast majority throughout the neuronal subsets and tissues examined. Furthermore, both the expression level and the proportion of GluR2 mRNA in motoneurons were the lowest among all neuronal subsets examined, whereas those in motoneurons of ALS did not differ from the control group, implying that selective reduction of the GluR2 subunit cannot be a mechanism of AMPA receptor-mediated neurotoxicity in ALS. However, the low relative abundance of GluR2 might provide spinal motoneurons with conditions that are easily affected by changes of AMPA receptor properties including deficient GluR2 mRNA editing in ALS.