Premium
Enhanced IL‐1β production in response to the activation of hippocampal glial cells impairs neurogenesis in aged mice
Author(s) -
Kuzumaki Naoko,
Ikegami Daigo,
Imai Satoshi,
Narita Michiko,
Tamura Rie,
Yajima Marie,
Suzuki Atsuo,
Miyashita Kazuhiko,
Niikura Keiichi,
Takeshima Hideyuki,
Ando Takayuki,
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.20800
Subject(s) - neurogenesis , neurod , dentate gyrus , hippocampal formation , neural stem cell , glial fibrillary acidic protein , hippocampus , microglia , biology , microbiology and biotechnology , neuroscience , epigenetic regulation of neurogenesis , chemistry , stem cell , epigenetics , cellular differentiation , immunology , inflammation , immunohistochemistry , biochemistry , histone methyltransferase , gene
Abstract A variety of mechanisms that contribute to the accumulation of age‐related damage and the resulting brain dysfunction have been identified. Recently, decreased neurogenesis in the hippocampus has been recognized as one of the mechanisms of age‐related brain dysfunction. However, the molecular mechanism of decreased neurogenesis with aging is still unclear. In the present study, we investigated whether aging decreases neurogenesis accompanied by the activation of microglia and astrocytes, which increases the expression of IL‐1β in the hippocampus, and whether in vitro treatment with IL‐1β in neural stem cells directly impairs neurogenesis. Ionized calcium‐binding adaptor molecule 1 (Iba1)‐positive microglia and glial fibrillary acidic protein (GFAP)‐positive astrocytes were increased in the dentate gyrus of the hippocampus of 28‐month‐old mice. Furthermore, the mRNA level of IL‐1β was significantly increased without related histone modifications. Moreover, a significant increase in lysine 9 on histone H3 (H3K9) trimethylation at the promoter of NeuroD (a neural progenitor cell marker) was observed in the hippocampus of aged mice. In vitro treatment with IL‐1β in neural stem cells prepared from whole brain of E14.5 mice significantly increased H3K9 trimethylation at the NeuroD promoter. These findings suggest that aging may decrease hippocampal neurogenesis via epigenetic modifications accompanied by the activation of microglia and astrocytes with the increased expression of IL‐1β in the hippocampus. Synapse 64:721–728, 2010. © 2010 Wiley‐Liss, Inc.