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Hippocampal epigenetic modification at the doublecortin gene is involved in the impairment of neurogenesis with aging
Author(s) -
Kuzumaki Naoko,
Ikegami Daigo,
Tamura Rie,
Sasaki Takuya,
Niikura Keiichi,
Narita Michiko,
Miyashita Kazuhiko,
Imai Satoshi,
Takeshima Hideyuki,
Ando Takayuki,
Igarashi Katsuhide,
Kanno Jun,
Ushijima Toshikazu,
Suzuki Tsutomu,
Narita Minoru
Publication year - 2010
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20768
Subject(s) - neurogenesis , doublecortin , epigenetics , hippocampal formation , neuroscience , biology , dentate gyrus , gene , genetics
Recent research has suggested that epigenetic mechanisms, which exert lasting control over gene expression without altering the genetic code, could mediate 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 2010. © 2010 Wiley‐Liss, Inc.