Genome-wide gene expression profiling in GluR1 knockout mice: key role of the calcium signaling pathway in glutamatergically mediated hippocampal transmission.
Genome-wide gene expression profiling in GluR1 knockout mice: key role of the calcium signaling pathway in glutamatergically mediated hippocampal transmission.
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GLUR1基因敲除小鼠中全基因组基因表达分析：谷氨酸能介导的海马传播中钙信号通路的关键作用。
DOI：
10.1111/j.1460-9568.2009.07022.x
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发表时间：
2009-12
期刊：
影响因子：
--
通讯作者：
Manji HK
中科院分区：
文献类型：
--
作者：
Zhou R;Holmes A;Du J;Malkesman O;Yuan P;Wang Y;Damschroder-Williams P;Chen G;Guitart X;Manji HK
α-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）受体在中枢神经系统（CNS）中传递快速突触传递并介导各种形式的海马可塑性。谷氨酸受体1型（GluR 1），AMPA受体家族的成员，破坏，导致突触改变和学习/记忆缺陷的小鼠。为了获得与GluR 1缺失相关的突触和行为变化的机制性见解，使用GluR 1敲除（KO）小鼠及其野生型同窝仔进行海马全基因组表达谱分析。发现38个基因的调节改变超过30%（p < 0.01，n=8），并且用另外的定量实验研究了这些基因中的7个。大部分改变的基因编码参与钙信号传导的分子，包括钙通道组分、钙结合蛋白和钙-钙调蛋白依赖性蛋白激酶II亚基。在蛋白质水平上，我们进一步评估了GluR 1基因敲除小鼠中钙通道中发生改变的一些基因。钙通道中的两个关键分子谷氨酸受体，离子型，N-甲基-D-天冬氨酸（NMDAR）-1和钙/钙调蛋白依赖性蛋白激酶II α（CAMK 2A）的蛋白质水平，表现出类似的变化，在mRNA水平上观察到的。这些发现提高了钙信号传导和其他可塑性分子可能有助于在GluR 1基因敲除小鼠中观察到的海马可塑性和行为缺陷的可能性。
α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors convey fast synaptic transmission in the central nervous system (CNS) and mediate various forms of hippocampal plasticity. Disruption of glutamate receptor type 1 (GluR1), a member of the AMPA receptor family, causes synaptic alterations and learning/memory deficits in mice. To gain mechanistic insight into the synaptic and behavioral changes associated with GluR1 deletion, hippocampal genome-wide expression profiling was conducted using groups of GluR1 knockout (KO) mice and their wild-type littermates. Regulation of 38 genes was found to be altered more than 30% (p < 0.01, n=8) and seven of these genes were studied with additional quantitative experiments. A large portion of the altered genes encoded molecules involved in calcium signaling, including calcium channel components, calcium binding proteins, and calcium-calmodulin-dependent protein kinase II subunit. At the protein level, we further evaluated some genes in the calcium pathway that were altered in GluR1 KO mice. Protein levels of two key molecules in the calcium pathway—glutamate receptor, ionotropic, N-methyl-D-aspartate (NMDAR)-1 and calcium/calmodulin-dependent protein kinase II alpha (CAMK2A), showed similar changes to those observed in mRNA levels. These findings raise the possibility that calcium signaling and other plasticity molecules may contribute to the hippocampal plasticity and behavioral deficits observed in GluR1 KO mice.
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影响因子：
--
作者：
Esteban, Jose A
通讯作者：
Esteban, Jose A
影响因子：
16.2
作者：
McCormack, SG;Stornetta, RL;Zhu, JJ
通讯作者：
Zhu, JJ
影响因子：
3
作者：
Bilke, S;Breslin, T;Sigvardsson, M
通讯作者：
Sigvardsson, M
影响因子：
11
作者：
Ryan, M. M.;Lockstone, H. E.;Bahn, S.
通讯作者：
Bahn, S.
DOI：
10.1073/pnas.96.6.3269
发表时间：
1999-03-16
影响因子：
11.1
作者：
Derkach, V;Barria, A;Soderling, TR
通讯作者：
Soderling, TR