High abundance of GluR1 mRNA and reduced Q/R editing of GluR2 mRNA in individual NADPH-diaphorase neurons
High abundance of GluR1 mRNA and reduced Q/R editing of GluR2 mRNA in individual NADPH-diaphorase neurons
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DOI：
10.1006/mcne.2001.0988
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发表时间：
2001-06-01
影响因子：
3.5
通讯作者：
Gwag, BJ
中科院分区：
文献类型：
--
作者：
Kim, DY;Kim, SH;Gwag, BJ
含有 NADPH-黄酶 [NADPH-d(+)] 的纹状体和皮质神经元非常容易受到由 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸 (AMPA) 或红藻氨酸敏感谷氨酸受体激活引起的兴奋性毒性。这归因于 Ca2+ 通过 NADPHd(+) 神经元中的 AMPA/红藻氨酸受体进入。在本研究中，我们应用单细胞 RT-PCR 技术来检验以下假设：GluR2 亚基水平和加工的差异会导致 NADPH-d(+) 神经元对 AMPA 的选择性脆弱性。 GluR1-GluR4特异性巢式PCR显示，大鼠纹状体NADPH-d(+)神经元表达的GluR1 mRNA是NADPH-d(-)神经元的两倍。 GluR2 Q/R 位点的 RNA 编辑百分比在 NADPH-d(+) 神经元中为 46%，在 NADPH-d(-) 神经元中为 92%。这些结果表明，未经编辑的 GluR2 表达结束了 GluR2/GluR1 比例的降低，使得 NADPH-d(+) 神经元对 Ca2+ 介导的 AMPA 神经毒性高度敏感。为了支持这一点，暴露于 100 muM AMPA 的大多数 NADPH-d(+) 神经元仅在缺乏细胞外 Ca2+ 的情况下才表现出 Co2+ 摄取并在 AMPA 攻击中存活。
Striatal and cortical neurons containing NADPH-diaphorase [NADPH-d(+)] are highly vulnerable to excitotoxicity that is induced by activation of alpha -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)- or kainate-sensitive glutamate receptors. This has been attributed to Ca2+ entry through AMPA/kainate receptors in NADPHd(+) neurons. In this study, we applied single cell RT-PCR technique to test the hypothesis that differences in levels and processing of the GluR2 subunit would contribute to the selective vulnerability of NADPH-d(+) neurons to AMPA. The nested PCR specific for GluR1-GluR4 showed that rat striatal NADPH-d(+) neurons expressed twice as much GluR1 mRNA as NADPH-d(-) neurons did. The percentage of RNA editing at the Q/R site of GluR2 was 46% in NADPH-d(+) neurons and 92% in NADPH-d(-) neurons. These results suggest that the unedited expression of GluR2 end the reduced ratio of GluR2/GluR1 render NADPH-d(+) neurons highly sensitive to Ca2+-mediated AMPA neurotoxicity. In support of this, most NADPH-d(+) neurons exposed to 100 muM AMPA showed Co2+ uptake and survived AMPA challenge only in the absence of extracellular Ca2+.