The immediate early gene early growth response gene 3 mediates adaptation to stress and novelty
The immediate early gene early growth response gene 3 mediates adaptation to stress and novelty
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DOI：
10.1016/j.neuroscience.2007.05.050
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发表时间：
2007-09-07
期刊：
影响因子：
3.3
通讯作者：
Milbrandt, J.
中科院分区：
文献类型：
--
作者：
Gallitano-Mendel, A.;Izumi, Y.;Milbrandt, J.
应激和探索新环境可诱导即时早期基因转录因子（ieg - tf）的神经表达。然而，到目前为止，还没有证据表明对这些刺激的正常生物或行为反应需要eeg - tf。本研究表明，缺乏IEG-TF早期生长反应基因（Egr） 3的小鼠，在处理轻度应激时表现出强化的行为反应，同时应激激素皮质酮的释放增加。Egr3-/-小鼠也表现出对新奇事物的异常反应，包括对新环境的反应增强，对社会线索或令人吃惊的声音刺激无法适应。在y形迷宫的自发交替任务中，他们比对照组执行更少的连续手臂输入，这表明他们在即时记忆方面存在缺陷。由于压力和新颖性刺激海马长期抑郁（LTD），并且由于对新颖性和y型迷宫表现的习惯异常与LTD缺陷有关，我们在Egr3-/-小鼠中研究了这种形式的突触可塑性。我们发现Egr3-/-小鼠在低频刺激下无法建立海马LTD，并表现出对伊芬丙地尔敏感（NR1/ NR2B） n -甲基- d -天冬氨酸受体亚类功能障碍。长时程增强诱导没有改变。NR2B依赖性功能障碍不是由Egr3对该亚基的转录调控引起的，因为在Egr3-/-和对照小鼠的海马中，NR2B mRNA水平没有差异。这些发现首次证明了eeg - tf在调节压力和新奇反应方面的需求，并在LTD. (c) 2007 IBRO的建立中得到了证实。Elsevier Ltd.出版。版权所有。
Stress and exploration of novel environments induce neural expression of immediate early gene transcription factors (IEG-TFs). However, as yet no IEG-TF has been shown to be required for the normal biological or behavioral responses to these stimuli. Here we show that mice deficient for the IEG-TF early growth response gene (Egr) 3, display accentuated behavioral responses to the mild stress of handling paralleled by increased release of the stress hormone corticosterone. Egr3-/- mice also display abnormal responses to novelty, including heightened reactivity to novel environments and failure to habituate to social cues or startling acoustic stimuli. In a Y-maze spontaneous alternation task, they perform fewer sequential arm entries than controls, suggesting defects in immediate memory. Because stress and novelty stimulate hippocampal long-term depression (LTD), and because abnormalities in habituation to novelty and Y-maze performance have been associated with LTD deficits, we examined this form of synaptic plasticity in Egr3-/- mice. We found that Egr3-/- mice fail to establish hippocampal LTD in response to low frequency stimulation and exhibit dysfunction of an ifenprodil-sensitive (NR1/ NR2B) N-methyl-D-aspartate receptor subclass. Long term potentiation induction was not altered. The NR2B-dependent dysfunction does not result from transcriptional regulation of this subunit by Egr3, because NR2B mRNA levels did not differ in the hippocampi of Egr3-/- and control mice. These findings are the first demonstration of the requirement for an IEG-TF in mediating the response to stress and novelty, and in the establishment of LTD. (c) 2007 IBRO. Published by Elsevier Ltd. All rights reserved.