Decreased GluR2(B) receptor subunit mRNA expression in cerebellar neurons at risk for degeneration.

Decreased GluR2(B) receptor subunit mRNA expression in cerebellar neurons at risk for degeneration.
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存在退化风险的小脑神经元中 GluR2(B) 受体亚基 mRNA 表达减少。

DOI:
10.1159/000111323
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发表时间:
1993
影响因子:
2.9
通讯作者:
Watson,JB
Watson,JB
中科院分区:
医学3区
文献类型:
--
作者:
Margulies,JE;Cohen,RW;Levine,MS;Watson,JB

文献摘要

被引文献

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GluR 2(GluR-B)水平相对于其他谷氨酸受体亚基的降低与非NMDA谷氨酸受体通道的Ca 2+渗透性增加相关。GluR 2通过这些通道介导的持续Ca 2+内流可能部分导致神经退行性疾病的发病机制。我们研究了突变型痉挛性汉-Wistar大鼠小脑谷氨酸受体亚单位(GluR 1 -7)mRNA的表达,其特征在于小脑浦肯野细胞的进行性变性和颗粒细胞层的紊乱。结合北方和狭缝印迹研究发现,相对于年龄匹配的小脑,突变小脑中GluR 2亚基表达降低。定量原位杂交研究表明,减少GluR 2 mRNA表达的浦肯野细胞(78%)和颗粒细胞层(70%)在30天的突变小脑的人口。由于有很少或没有迹象表明,在这个年龄段的突变小脑细胞变性,我们建议,减少GluR 2 mRNA表达在汉Wistar小脑细胞反映了改变谷氨酸受体,可能aberrantly流量Ca 2+,从而有助于进行性神经元变性。
A decrease in levels of GluR2 (GluR-B) relative to other glutamate receptor subunits is correlated with increased Ca2+permeability of non-NMDA glutamate receptor channels. Sustained Ca2+influx mediated by GluR2 through these channels may contribute partly to the pathogenesis of neurodegenerative disorders. We examined the expression of glutamate receptor subunit (GluR1–7) mRNAs in the cerebellum of the mutant spastic Han-Wistar rat which is characterized by a progressive degeneration of cerebellar Purkinje cells and disarrangement of the granule cell layer. Combined Northern and slot blot studies detected decreased GluR2 subunit expression in mutant cerebellum relative to age-matched cerebellum. Quantitative in situ hybridization studies revealed decreased GluR2 mRNA expression in a population of Purkinje cells (78%) and in the granule cell layer (70%) in 30-day-old mutant cerebellum. Since there is little or no sign of cellular degeneration in mutant cerebellum at this age, we propose that decreased GluR2 mRNA expression in Han-Wistar cerebellar cells reflects an altered glutamate receptor that may aberrantly flux Ca2+and thus contribute to progressive neuronal degeneration.