SWITCH IN GLUTAMATE RECEPTOR SUBUNIT GENE-EXPRESSION IN CA1 SUBFIELD OF HIPPOCAMPUS FOLLOWING GLOBAL-ISCHEMIA IN RATS
SWITCH IN GLUTAMATE RECEPTOR SUBUNIT GENE-EXPRESSION IN CA1 SUBFIELD OF HIPPOCAMPUS FOLLOWING GLOBAL-ISCHEMIA IN RATS
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DOI：
10.1073/pnas.89.21.10499
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发表时间：
1992-11-01
影响因子：
11.1
通讯作者：
PULSINELLI, WA
中科院分区：
文献类型：
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作者：
PELLEGRINIGIAMPIETRO, DE;ZUKIN, RS;PULSINELLI, WA
严重的、短暂的全脑缺血诱导对特定神经元群体的迟发性损伤。通过谷氨酸受体通道的持续Ca 2+内流被认为在缺血后细胞死亡中起关键作用。尽管大多数红藻氨酸型谷氨酸受体是Ca 2+不可渗透的，但据报道，Ca 2+可渗透的红藻氨酸受体存在于特定类型的神经元和神经胶质中。在外源表达系统中由GluR 1和/或GluR 3亚基组装的重组受体对Ca 2+是可渗透的;含有GluR 2亚基的异聚体通道是Ca 2+不可渗透的。因此，在发育过程中或神经损伤或脑损伤后，GluR 2表达的改变可以作为改变Ca 2+渗透性的开关。为了探讨延迟性脑缺血后细胞死亡的分子机制，GluR 1，GluR 2和GluR 3基因的表达进行了研究，通过原位杂交在脑缺血后大鼠。严重的，短暂的前脑缺血GluR 2基因表达优先减少在CA 1海马神经元的时间点之前，他们的变性。红藻氨酸/AMPA受体亚基表达的开关与先前报道的Ca 2+流入CA 1细胞的增加相一致。开关的时间表明，它可能在缺血后细胞死亡中发挥因果作用。
Severe, transient global ischemia of the brain induces delayed damage to specific neuronal populations. Sustained Ca2+ influx through glutamate receptor channels is thought to play a critical role in postischemic cell death. Although most kainate-type glutamate receptors are Ca2+-impermeable, Ca2+-permeable kainate receptors have been reported in specific kinds of neurons and glia. Recombinant receptors assembled from GluR1 and/or GluR3 subunits in exogenous expression systems are permeable to Ca2+; heteromeric channels containing GluR2 subunits are Ca2+-impermeable. Thus, altered expression of GluR2 in development or following a neurological insult or injury to the brain can act as a switch to modify Ca2+ permeability. To investigate the molecular mechanism underlying delayed postischemic cell death, GluR1, GluR2, and GluR3 gene expression was examined by in situ hybridization in postischemic rats. Following severe, transient forebrain ischemia GluR2 gene expression was preferentially reduced in CA1 hippocampal neurons at a time point that preceded their degeneration. The switch in expression of kainate/AMPA receptor subunits coincided with the previously reported increase in Ca2+ influx into CA1 cells. Timing of the switch indicates that it may play a causal role in postischemic cell death.