Acute reduction of neuronal RNA binding Elavl2 protein and Gap43 mRNA in mouse hippocampus after kainic acid treatment
Acute reduction of neuronal RNA binding Elavl2 protein and Gap43 mRNA in mouse hippocampus after kainic acid treatment
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DOI：
10.1016/j.bbrc.2015.08.103
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发表时间：
2015-10-09
影响因子：
3.1
通讯作者：
Okano, Hideyuki
中科院分区：
文献类型：
--
作者：
Ohtsuka, Takafumi;Yano, Masato;Okano, Hideyuki
神经元中的活性依赖性基因调控被假设为在转录控制下，并且包括在神经元活性之后立即早期基因（IEG）的急剧增加。此外，一些报告集中在转录后调节，这可能是由神经元转录后调节因子，包括RNA结合蛋白（RNABP）介导的。一个这样的蛋白质家族是神经元Elavl（nElavl; Elavl 2、Elavl 3和Elavl 4），其成员在外周和中枢神经系统中广泛表达。先前的报道表明，Elavl 3和4在重复刺激后上调，例如在可卡因施用、癫痫发作或空间辨别任务期间。在这项研究中，我们专注于Elavl 2，精神分裂症的候选基因，并研究其在神经元活动中的作用。首先，我们使用Elavl 2特异性抗体发现Elavl 2具有细胞类型特异性表达模式，其在海马CA 3锥体神经元和门部中间神经元中高度表达。第二，出乎意料地，我们发现，在海马CA 3区海人酸（KA）诱导的癫痫发作后，海马中的Elavl 2蛋白水平急剧下调3小时。另外，在KA处理后12 h，Elavl 2的靶mRNA Gap 43 mRNA的水平降低，从而表明Elavl 2参与活性依赖性RNA调节。(C)2015 Elsevier Inc. All rights reserved.
Activity-dependent gene regulation in neurons has been hypothesized to be under transcriptional control and to include dramatic increases in immediate early genes (IEGs) after neuronal activity. In addition, several reports have focused on post-transcriptional regulation, which could be mediated by neuronal post-transcriptional regulators, including RNA binding proteins (RNABPs). One such protein family is the neuronal Elavls (nElavls; Elavl2, Elavl3, and Elavl4), whose members are widely expressed in peripheral and central nervous system. Previous reports showed that Elavl3 and 4 are up-regulated following repeated stimulation such as during cocaine administration, a seizure, or a spatial discrimination task. In this study, we focused on Elavl2, a candidate gene for schizophrenia and studied its role in neuronal activity. First we found that Elavl2 has a cell-type specific expression pattern that is highly expressed in hippocampal CA3 pyramidal neurons and hilar interneurons using Elavl2 specific antibody. Second, unexpectedly, we discovered that the Elavl2 protein level in the hippocampus was acutely downregulated for 3 h after a kainic acid (KA)-induced seizure in the hippocampal CA3 region. In addition, level of Gap43 mRNA, a target mRNA of Elavl2 is decreased 12 h after KA treatment, thus suggesting the involvement of Elavl2 in activity-dependent RNA regulation. (C) 2015 Elsevier Inc. All rights reserved.