Impaired extinction of learned contextual fear memory in early growth response 1 knockout mice.
Impaired extinction of learned contextual fear memory in early growth response 1 knockout mice.
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DOI：
10.14348/molcells.2014.2206
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发表时间：
2014-01
影响因子：
3.8
通讯作者：
Kim H
中科院分区：
文献类型：
--
作者：
Han S;Hong S;Mo J;Lee D;Choi E;Choi JS;Sun W;Lee HW;Kim H
早期生长反应1 （Egr-1）在神经元中的诱导表达与多种形式的神经元活动有关。然而，只有少数Egr-1靶基因在大脑中是已知的。本研究结果表明，与野生型（WT）对照动物相比，Egr-1基因敲除（KO）小鼠表现出上下文灭绝学习受损和正常恐惧习得。全基因组微阵列实验显示，与KO小鼠海马基因表达谱相比，暴露于恐惧条件反射范式不同阶段的Egr-1 WT海马中存在368个差异表达基因。一些基因，如5 -羟色胺受体2C （Htr2c）、神经肽B （Npb）、神经元PAS结构域蛋白4 （Npas4）、NPY受体Y1 （Npy1r）、脂肪酸结合蛋白7 （Fabp7）和神经肽Y (NPY)，已知可以调节恐惧记忆的加工，启动子分析表明，其中一些基因含有Egr-1结合位点。本研究为恐惧记忆加工过程中可能受到调控的Egr-1靶基因提供了一个有用的列表。
Inductive expression of early growth response 1 (Egr-1) in neurons is associated with many forms of neuronal activity. However, only a few Egr-1 target genes are known in the brain. The results of this study demonstrate that Egr-1 knockout (KO) mice display impaired contextual extinction learning and normal fear acquisition relative to wild-type (WT) control animals. Genome-wide microarray experiments revealed 368 differentially expressed genes in the hippocampus of Egr-1 WT exposed to different phases of a fear conditioning paradigm compared to gene expression profiles in the hippocampus of KO mice. Some of genes, such as serotonin receptor 2C (Htr2c), neuropeptide B (Npb), neuronal PAS domain protein 4 (Npas4), NPY receptor Y1 (Npy1r), fatty acid binding protein 7 (Fabp7), and neuropeptide Y (Npy) are known to regulate processing of fearful memories, and promoter analyses demonstrated that several of these genes contained Egr-1 binding sites. This study provides a useful list of potential Egr-1 target genes which may be regulated during fear memory processing.