Hippocampal Epigenetic Modification at the Doublecortin Gene is Involved in the Impairment of Neurogenesis With Aging
Hippocampal Epigenetic Modification at the Doublecortin Gene is Involved in the Impairment of Neurogenesis With Aging
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DOI：
10.1002/syn.20768
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发表时间：
2010-08-01
期刊：
影响因子：
2.3
通讯作者：
Narita, Minoru
中科院分区：
文献类型：
--
作者：
Kuzumaki, Naoko;Ikegami, Daigo;Narita, Minoru
最近的研究表明，表观遗传机制，施加持久的控制基因的表达，而不改变遗传密码，可以介导稳定的变化，在脑功能越来越多的证据支持的想法，表观遗传的变化发挥作用的病因学老化及其相关的脑功能障碍。本研究旨在评估老年小鼠海马中doublecortin表达的年龄相关变化，doublecortin是神经元前体的标志物，沿着表观遗传修饰。在本研究中，28月龄小鼠海马齿状回几乎完全不存在doublecortin阳性细胞。此外，老龄小鼠海马区doublecortin mRNA表达水平显著降低。在这些条件下，观察到随着年龄的增长，在双皮质素启动子处H3 K4三甲基化的显著减少和H3 K27三甲基化的显著增加，而海马中与其相关的组蛋白甲基化酶和去甲基化酶的表达没有任何变化。这些发现表明，随着海马中表观遗传修饰的增加，衰老引起双皮质素沿着表达的显著减少。Synapse 64：611-616，2010.（C）2010 Wiley-Liss，Inc
Recent research has suggested that epigenetic mechanisms, which exert lasting control over gene expression without altering the genetic code, could mediase stable changes in brain function A growing body of evidence supports the idea that epigenetic changes play a role in the etiology of aging and its associated brain dysfunction. The present study was undertaken to evaluate the age-related changes in the expression of doublecortin, which is a marker for neuronal precursors, along with epigenetic modification in the hippocampus of aged mice In the present study, the doublecortin-positive cells were almost completely absent from the dentate gyrus of the hippocampus of 28-month-old mice. Furthermore, the expression level of doublecortin mRNA was significantly decreased in the hippocampus of aged mice. Under these conditions, a significant decrease in H3K4 trimethylation and a significant increase in H3K27 trimethylation at doublecortin promoters were observed with aging without any changes in the expression of their associated histone methylases and demethylases in the hippocampus These findings suggest that aging produces a dramatic decrease in the expression of doublecortin along with epigenetic modifications in the hippocampus. Synapse 64:611-616, 2010. (C)2010 Wiley-Liss, Inc