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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2010-7-15
pubmed:abstractText
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-1beta in the hippocampus, and whether in vitro treatment with IL-1beta 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-1beta 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-1beta 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-1beta in the hippocampus.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1098-2396
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
64
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
721-8
pubmed:meshHeading
pubmed-meshheading:20336624-Aging, pubmed-meshheading:20336624-Animals, pubmed-meshheading:20336624-Astrocytes, pubmed-meshheading:20336624-Cell Differentiation, pubmed-meshheading:20336624-DNA, pubmed-meshheading:20336624-Female, pubmed-meshheading:20336624-Fluorescent Antibody Technique, pubmed-meshheading:20336624-Hippocampus, pubmed-meshheading:20336624-Immunohistochemistry, pubmed-meshheading:20336624-Interleukin-1beta, pubmed-meshheading:20336624-Mice, pubmed-meshheading:20336624-Mice, Inbred C57BL, pubmed-meshheading:20336624-Neurogenesis, pubmed-meshheading:20336624-Neuroglia, pubmed-meshheading:20336624-Pregnancy, pubmed-meshheading:20336624-Protein Array Analysis, pubmed-meshheading:20336624-RNA, pubmed-meshheading:20336624-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:20336624-Stem Cells
pubmed:year
2010
pubmed:articleTitle
Enhanced IL-1beta production in response to the activation of hippocampal glial cells impairs neurogenesis in aged mice.
pubmed:affiliation
Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
pubmed:publicationType
Journal Article