Hippocampal Epigenetic Modification at the Doublecortin Gene is Involved in the Impairment of Neurogenesis With Aging

被引：22

作者：

Kuzumaki, Naoko ^{[1
]}

Ikegami, Daigo ^{[1
]}

Tamura, Rie ^{[1
]}

Sasaki, Takuya ^{[1
]}

Niikura, Keiichi ^{[1
]}

Narita, Michiko ^{[1
]}

Miyashita, Kazuhiko ^{[1
]}

Imai, Satoshi ^{[1
]}

Takeshima, Hideyuki ^{[2
]}

Ando, Takayuki ^{[2
]}

Igarashi, Katsuhide ^{[3
]}

Kanno, Jun ^{[3
]}

Ushijima, Toshikazu ^{[2
]}

Suzuki, Tsutomu ^{[1
]}

Narita, Minoru ^{[1
]}

机构：

[1] Hoshi Univ, Sch Pharm & Pharmacal Sci, Dept Toxicol, Shinagawa Ku, Tokyo 1428501, Japan

[2] Natl Canc Ctr, Res Inst, Carcirogenesis Div, Chuo Ku, Tokyo 1040045, Japan

[3] Natl Inst Hlth Sci, Biol Safety Res Ctr, Div Cellular & Mol Toxicol, Setagaya Ku, Tokyo 1540000, Japan

来源：

SYNAPSE | 2010年 / 64卷 / 08期

关键词：

senescent; mouse hippocampus; epigenome; DCX; neurogenesis; DENTATE GYRUS; NEURONS; PROLIFERATION; ZONE;

D O I：

10.1002/syn.20768

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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

引用

页码：611 / 616

页数：6

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