Novelty stress induces phospho-acetylation of histone H3 in rat dentate gyrus granule neurons through coincident signalling via the N-methyl-D-aspartate receptor and the glucocorticoid receptor:: relevance for c-fos induction
Novelty stress induces phospho-acetylation of histone H3 in rat dentate gyrus granule neurons through coincident signalling via the N-methyl-D-aspartate receptor and the glucocorticoid receptor:: relevance for c-fos induction
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DOI：
10.1111/j.1471-4159.2006.04396.x
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发表时间：
2007-05-01
影响因子：
4.7
通讯作者：
Reul, Johannes M. H. M.
中科院分区：
文献类型：
--
作者：
Chandramohan, Yalini;Droste, Susanne K.;Reul, Johannes M. H. M.
海马体在新奇事物发现、压力相关适应以及学习和记忆中发挥着重要作用。然而，目前尚不清楚海马体对新奇事物的反应是否涉及诱导已知与转录调控相关的染色质重塑事件。在这里，我们检查了暴露于新环境（轻微的心理压力源）是否会影响大鼠海马中磷酸乙酰化组蛋白 H3 阳性 [P(Ser10)-Ac(Lys14)-H3(+)] 神经元的数量。我们发现：（i）压力情况导致 P(Ser10)-Ac(Lys14)-H3(+) 神经元数量显着增加，特别是在齿状回中； (ii) 应激诱导的 P(Ser10)-Ac(Lys14)-H3(+) 神经元的增加发生在整个海马头尾轴的齿状回中，但它们仅位于齿状回上叶颗粒细胞层的中部和浅层； (iii) NMDA或糖皮质激素受体的拮抗作用，但不是盐皮质激素受体的拮抗作用或一氧化氮合成的抑制作用，减弱了应激诱导的反应； (iv) 联合阻断 NMDA 和糖皮质激素受体可消除应激诱导的组蛋白修饰反应； (v) 此外，这种联合封锁还消除了应激后 P(Ser10)-Ac(Lys14)-H3 相关基因产物 c-fos 的诱导； (vi)给未受应激的大鼠施用皮质酮不影响组蛋白H3磷酸乙酰化。因此，新奇应激通过 NMDA 受体和糖皮质激素受体的并发信号传导，诱导成熟齿状神经元染色质重塑和 c-fos 诱导。
The hippocampus plays an important role in novelty detection, stress-related adaptation and learning and memory. However, it is unknown whether the response to novelty in the hippocampus involves induction of chromatin remodelling events known to be associated with transcriptional regulation. Here, we examined whether exposure to a novel environment, a mild psychological stressor, would affect the number of phospho-acetylated histone H3-positive [P(Ser10)-Ac(Lys14)-H3(+)] neurons in the rat hippocampus. We show that: (i) the stressful situation induced a marked increase in the number of P(Ser10)-Ac(Lys14)-H3(+) neurons, specifically in the dentate gyrus; (ii) the stress-induced rise in P(Ser10)-Ac(Lys14)-H3(+) neurons occurred in the dentate gyrus throughout the rostro-caudal axis of the hippocampus, but they were exclusively located in the middle and superficial aspects of the granular cell layer of the upper blade of the dentate gyrus; (iii) antagonism of NMDA or glucocorticoid receptors, but not antagonism of mineralocorticoid receptors or inhibition of nitric oxide synthesis, attenuated the stress-induced response; (iv) combined blockade of NMDA and glucocorticoid receptors ablated the stress-induced histone modification response; (v) moreover, this combined blockade also abolished the induction of the P(Ser10)-Ac(Lys14)-H3-associated gene product c-fos after stress; (vi) administration of corticosterone to unstressed rats did not affect histone H3 phospho-acetylation. Thus, novelty stress induces chromatin remodelling and c-fos induction in mature dentate neurons through concurrent signalling via the NMDA receptor and the glucocorticoid receptor.