Distinct epigenetic and gene expression changes in rat hippocampal neurons after Morris water maze training.
Distinct epigenetic and gene expression changes in rat hippocampal neurons after Morris water maze training.
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DOI：
10.3389/fnbeh.2015.00156
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发表时间：
2015
影响因子：
3
通讯作者：
Reul JM
中科院分区：
文献类型：
--
作者：
Carter SD;Mifsud KR;Reul JM
海马中的基因转录和翻译在包括Morris水迷宫（MWM）学习过程中的海马依赖性记忆形成中至关重要。先前使用基因缺失模型的工作表明，立即早期基因（IEGs）c-Fos，Egr-1和Arc对这种学习至关重要。最近，我们报道了在稀疏齿状回神经元中诱导IEGs需要ERK MAPK信号传导和下游形成不同的表观遗传组蛋白标记（即，磷酸乙酰化组蛋白H3）。迄今为止，在MWM模型中还没有对这一信号传导、表观遗传和基因转录途径进行全面的研究。因此，我们进行了详细的研究ERK 1/2和丝氨酸10的磷酸化组蛋白H3（H3 S10 p）和诱导的IEGs在MWM训练大鼠和匹配的对照海马。MWM训练诱发连续波的ERK 1/2磷酸化和H3 S10磷酸化，以及c-Fos，Egr-1和Arc诱导稀疏海马神经元。所观察到的效应在齿状回中最为明显。发现平台的平均潜伏期与H3 S10 p阳性齿状回神经元的数量呈正相关。此外，染色质免疫沉淀（ChIP）显示磷酸乙酰化组蛋白H3（H3 K9 ac-S10 p）与c-Fos和Egr-1的基因启动子，但不是弧，与对照组相比，MWM暴露后显着增加的协会。然而，令人惊讶的是，我们发现与匹配的游泳对照组相比，MWM训练大鼠的IEG反应（关于蛋白质和mRNA）之间的差异很小。我们的结论是，暴露于水迷宫引起ERK MAPK激活，明显的表观遗传变化和IEG诱导主要在稀疏的齿状回神经元。然而，似乎在MWM训练的学习方面IEG的特定作用可能在下游AP-1和Egr-1调节（第二波）基因和ARC依赖效应器机制中变得明显。
Gene transcription and translation in the hippocampus is of critical importance in hippocampus-dependent memory formation, including during Morris water maze (MWM) learning. Previous work using gene deletion models has shown that the immediate-early genes (IEGs) c-Fos, Egr-1, and Arc are crucial for such learning. Recently, we reported that induction of IEGs in sparse dentate gyrus neurons requires ERK MAPK signaling and downstream formation of a distinct epigenetic histone mark (i.e., phospho-acetylated histone H3). Until now, this signaling, epigenetic and gene transcriptional pathway has not been comprehensively studied in the MWM model. Therefore, we conducted a detailed study of the phosphorylation of ERK1/2 and serine10 in histone H3 (H3S10p) and induction of IEGs in the hippocampus of MWM trained rats and matched controls. MWM training evoked consecutive waves of ERK1/2 phosphorylation and H3S10 phosphorylation, as well as c-Fos, Egr-1, and Arc induction in sparse hippocampal neurons. The observed effects were most pronounced in the dentate gyrus. A positive correlation was found between the average latency to find the platform and the number of H3S10p-positive dentate gyrus neurons. Furthermore, chromatin immuno-precipitation (ChIP) revealed a significantly increased association of phospho-acetylated histone H3 (H3K9ac-S10p) with the gene promoters of c-Fos and Egr-1, but not Arc, after MWM exposure compared with controls. Surprisingly, however, we found very little difference between IEG responses (regarding both protein and mRNA) in MWM-trained rats compared with matched swim controls. We conclude that exposure to the water maze evokes ERK MAPK activation, distinct epigenetic changes and IEG induction predominantly in sparse dentate gyrus neurons. It appears, however, that a specific role for IEGs in the learning aspect of MWM training may become apparent in downstream AP-1- and Egr-1-regulated (second wave) genes and Arc-dependent effector mechanisms.
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影响因子：
4.7
作者：
Chandramohan, Yalini;Droste, Susanne K.;Reul, Johannes M. H. M.
通讯作者：
Reul, Johannes M. H. M.
DOI：
10.1186/1744-9081-6-35
发表时间：
2010-07-02
期刊：
Behavioral and brain functions : BBF
影响因子：
--
作者：
Feldman LA;Shapiro ML;Nalbantoglu J
通讯作者：
Nalbantoglu J
影响因子：
2
作者：
Chwang, Wilson B.;O'Riordan, Kenneth J.;Sweatt, J. David
通讯作者：
Sweatt, J. David
影响因子：
3.4
作者：
Bilang-Bleuel, A;Ulbricht, S;Reul, JMHM
通讯作者：
Reul, JMHM
影响因子：
25
作者：
Jones, MW;Errington, ML;Davis, S
通讯作者：
Davis, S