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Series GSE56452 Query DataSets for GSE56452
Status Public on Oct 01, 2014
Title SIRT1 deficiency in microglia contributes to cognitive decline in aging and neurodegeneration via epigenetic regulation of IL-1beta
Organism Mus musculus
Experiment type Expression profiling by array
Summary Aging is the predominant risk factor for neurodegenerative diseases. One key phenotype as brain ages is the aberrant innate immune response characterized by proinflammation. However, the molecular mechanisms underlying aging-associated proinflammation are poorly defined. Whether chronic inflammation plays a causal role in cognitive decline in aging and neurodegeneration has not been established. Here we established a mechanistic link between chronic inflammation and aging microglia, and demonstrated a causal role of aging microglia in neurodegenerative cognitive deficits. Expression of microglial SIRT1 reduces with the aging of microglia. Genetic reduction of microglial SIRT1 elevates IL-1β selectively, and exacerbates cognitive deficits in aging and in transgenic mouse models of frontotemporal dementia (FTD). Interestingly, the selective activation of IL-1β transcription by SIRT1 deficiency is likely mediated through hypomethylating the proximal promoter of IL-1β. Consistent with our findings in mice, selective hypomethylation of IL-1β at two CpG sites are found in normal aging humans and demented patients with tauopathy. Our findings reveal a novel epigenetic mechanism in aging microglia that contributes to cognitive deficits in neurodegenerative diseases.
 
Overall design Study of changes related to alterations of SIRT1 levels in microglia of young and aged animals and in models of neurodegenerative dementia
 
Contributor(s) Cho S, Chen J, Ward ME, Gao F, Krabbe G, Sohn PD, Lo I, Minami S, Devidze N, Zhou Y, Coppola G, Gan L
Citation(s) 25589773
Submission date Apr 02, 2014
Last update date Jun 14, 2018
Contact name Giovanni Coppola
E-mail(s) gcoppola@ucla.edu
Phone 310-794-4172
Organization name UCLA
Department Psychiatry and Neurology
Lab Neurogenetics
Street address 1524 Gonda, 695 Charles Young Drive South
City Los Angeles
State/province CA
ZIP/Postal code 90095
Country USA
 
Platforms (1)
GPL6885 Illumina MouseRef-8 v2.0 expression beadchip
Samples (16)
GSM1361729 1.SIRT1 young
GSM1361730 2.SIRT1 young
GSM1361731 3.SIRT1 young
Relations
BioProject PRJNA243353

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE56452_RAW.tar 3.1 Mb (http)(custom) TAR
GSE56452_non-normalized.txt.gz 1.7 Mb (ftp)(http) TXT
Raw data are available on Series record
Processed data included within Sample table

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