Psychological stress increases histone H3 phosphorylation in adult dentate gyrus granule neurons: involvement in a glucocorticoid receptor-dependent behavioural response
Psychological stress increases histone H3 phosphorylation in adult dentate gyrus granule neurons: involvement in a glucocorticoid receptor-dependent behavioural response
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DOI：
10.1111/j.1460-9568.2005.04358.x
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发表时间：
2005-10-01
影响因子：
3.4
通讯作者：
Reul, JMHM
中科院分区：
文献类型：
--
作者：
Bilang-Bleuel, A;Ulbricht, S;Reul, JMHM
与沉默基因转录激活相关的染色质重塑涉及核小体蛋白组蛋白H3的N末端丝氨酸-10的磷酸化和赖氨酸-14的乙酰化。我们已发现主要位于齿状回的神经元对磷酸化组蛋白H3[即P(Ser10)-H3]和磷酸化的组蛋白H3[即P(Ser10)-Ac(Lys14)-H3]显示出斑点状的核免疫反应模式。强迫游泳增加了大鼠和小鼠齿状回P(Ser10)-H3阳性神经元的数量。暴露于捕食者的小鼠也有类似的效果，但暴露在乙醚蒸汽或寒冷环境中的大鼠P(Ser10)-H3(+)齿状神经元的数量没有变化，表明应激对组蛋白H3磷酸化的影响是应激源特有的。强迫游泳诱导的齿状回P(Ser10)-H3(+)神经元在8~24 h达到高峰，仅限于Neun(+)(即成熟)神经元，主要发生在颗粒细胞层的中层和浅层。此外，这种增加表现出刺激强度依赖(即在19摄氏度游泳比在25摄氏度游泳产生更大的增加)，并可被糖皮质激素受体(GR)拮抗剂RU 38486和ORG 34517阻断。在本实验条件下，当在最初的强迫游泳实验后24小时重新测试强迫游泳诱发的行为不动反应时，观察到齿状回颗粒神经元中组蛋白H3的磷酸化与获得性不动反应之间存在显著的相关性。我们的数据表明，具有强烈心理成分的应激事件，如强迫游泳，在成熟的齿状回颗粒神经元中引起明显的GR依赖的组蛋白修饰，这可能参与了有机体对这一事件的行为适应。
Chromatin remodelling associated with transcriptional activation of silent genes involves phosphorylation at Serine-10 and acetylation at Lysine-14 in the N-terminal tails of the nucleosomal protein histone H3. We have identified neurons predominantly in the dentate gyrus showing a speckled nuclear immunoreactivity pattern for phosphorylated histone H3 [i.e. P(Ser10)-H3] and phospho-acetylated histone H3 [i.e. P(Ser10)-Ac(Lys14)-H3]. Forced swimming increased the number of P(Ser10)-H3-positive [P(Ser10)-H3(+)] neurons in the rat and mouse dentate gyrus. Exposure of mice to a predator had a similar effect, but exposing rats to ether vapour or a cold environment evoked no change in the number of P(Ser10)-H3(+) dentate neurons, indicating that the effect of stress on histone H3 phosphorylation is stressor-specific. The forced swimming-induced increase in dentate P(Ser10)-H3(+) neurons peaked at 8-24 h, was restricted to NeuN(+) (i.e. mature) neurons, and occurred mainly in the middle and superficial aspects of the granular cell layer. Moreover, this increase showed stimulus strength dependency (i.e. swimming at 19 degrees C produced a larger increase than swimming at 25 degrees C) and could be blocked by the glucocorticoid receptor (GR) antagonists RU 38486 and ORG 34517. Under these experimental conditions, when the forced swimming-induced behavioural immobility response was determined in a re-test 24 h after the initial forced swim test, striking correlations were observed between the phosphorylation of histone H3 in dentate gyrus granule neurons and the acquired immobility response. Our data indicate that stressful events with a strong psychological component such as forced swimming evoke distinct GR-dependent histone modifications in mature dentate gyrus granule neurons that may participate in the behavioural adaptation of the organism to this event.