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Series GSE113539 Query DataSets for GSE113539
Status Public on May 01, 2019
Title IL-1β driven amyloid plaque clearance is associated with an expansion of transcriptionally reprogrammed microglia
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Neuroinflammation is thought to contribute to the pathogenesis of Alzheimer’s disease (AD), yet numerous studies have demonstrated a beneficial role for neuroinflammation in amyloid plaque clearance. We have previously shown that sustained expression of IL-1β in the hippocampus of APP/PS1 mice decreases amyloid plaque burden independent of recruited CCR2+ myeloid cells, suggesting resident microglia as the main phagocytic effectors of IL-1β-induced plaque clearance. To date, however, the mechanisms of IL-1β-induced plaque clearance remain poorly understood. To determine whether IL-1β-induced plaque clearance is due to enhanced microglial phagocytosis of Aβ, APP/PS1 mice induced to express mature human IL-1β in the hippocampus via adenoviral transduction were treated with the Aβ fluorescent probe methoxy-X04 (MX04) and microglial internalization of Aβ was analyzed by flow cytometry and immunohistochemistry. We found that resident microglia (CD45loCD11b+) constituted >70% of the MX04+ cells in both control and IL-1β-treated conditions, and that <10% of MX04+ cells were recruited myeloid cells (CD45hiCD11b+). However, we found that IL-1β treatment did not augment the percentage of MX04+ microglia nor the quantity of Aβ internalized by individual microglia. Instead, we found that IL-1β treatment resulted in a significant increase in the total number of MX04+ microglia in the hippocampus due to IL-1β-induced proliferation. Consistent with these results, transcriptomic analyses revealed very similar gene expression profiles between MX04+ and MX04- microglia, indicating IL-1β does not drive enhanced expression of phagocytosis-related genes. By contrast, IL-1β treatment was associated with large-scale changes in the expression of genes related to proliferation, immune function and inflammation. Together, these studies demonstrate that IL-1β induces microglial proliferation and the expression of genes involved in inflammatory immune functions that may be related to Aβ clearance.
Overall design Hippocampal microglia mRNA profiles of 8-month-old APP/PS1-rAAV2-Phe and APP/PS1-rAAV2-IL-1β further sorted on MX04+ (Aβ+) and MX04- (Aβ-). Two biological replicates of pooled cells from 6-8 APP/PS1 mouse hippocampi for each experimental group were sequenced using the Illumina HiSeq 2500.
Contributor(s) Rivera-Escalera F, O'Banion MK
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Submission date Apr 23, 2018
Last update date May 01, 2019
Contact name M. Kerry O'Banion
Organization name University of Rochester
Department Neuroscience
Street address 601 Elmwood Avenue
City Rochester
State/province NY
ZIP/Postal code 14642
Country USA
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (8)
GSM3108742 AD-Phe MX04 Neg 1
GSM3108743 AD-Phe MX04 Neg 2
GSM3108744 AD-Phe MX04 Pos 1
BioProject PRJNA451478
SRA SRP142316

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Supplementary file Size Download File type/resource
GSE113539_rawCounts.txt.gz 204.4 Kb (ftp)(http) TXT
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