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Series GSE167610 Query DataSets for GSE167610
Status Public on Feb 27, 2021
Title Brain Genexpession of a mouse modle of Sepsis-associated encephalopathy (SAE)
Organism Mus musculus
Experiment type Expression profiling by array
Summary Sepsis-associated encephalopathy (SAE) is a major and frequent complication in patients with sepsis resulting in delirium and premature death. Sepsis survivors commonly suffer from long-term cognitive impairment causing immense burden on patients, caregivers, and economic health systems. Underlying pathophysiology of SAE related cognitive deficits is largely unresolved, Thus treatment options are missing. We report that experimental polymicrobial sepsis in mice induces synaptic pathology in the central nervous system underlying defective long-term potentiation and cognitive dysfunction. Analysis of differentially expressed genes revealed severely affected downregulation of genes related to neuronal and synaptic signaling in the brain, e.g. of the activity-regulated cytoskeleton-associated protein (Arc ), of the transcription-regulatory EGR family, and of the dual-specificity phosphatase 6 (Dusp6). On the protein level, ARC expression and mitogen-activated protein (MAP) kinase signaling in the brain was disturbed during SAE. For targeted rescue of dysregulated synaptic signaling and plasticity, we overexpressed ARC in the hippocampus by bilateral in-vivo stereotactic microinjection of an adeno-associated virus containing a neuron-specific plasmid of the Arc transgene. Hereby, defective synaptic plasticity and signaling in the hippocampus were restored and memory function improved. Accordingly, synaptic plasticity, neuronal spine pathology, and memory dysfunction also improved when post-septic mice were subjected to enriched environment demonstrating the potential for activity-induced recovery of long-term cognitive dysfunction. Together, we identified synaptic pathology of neurocognitive dysfunction after severe systemic infection and provide a proof-of-concept approach to interfere with SAE pathomechanisms leading to cognitive improvement.
 
Overall design In total the RNA of 16 mice was analzyed. In 8 mice an experimental polymicrobial sepsis was induced. In 4 mice the expression was analyzed during the acute Phase 3 days after sepsis induction. Antother 4 mices survived 10 weeks. 4 and 4 mice receiving the same antibiotic treatment served as control.
 
Contributor(s) Grünewald B, Hörhold F, Blaess M, Hempel R, König R, Geis C
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Submission date Feb 26, 2021
Last update date Mar 02, 2021
Contact name Markus Blaess
E-mail(s) markus.blaess@web.de
Organization name Furtwangen University
Department Institute of Precision Medicine
Street address Jakob-Kienzle-Strasse 17
City Villingen-Schwenningen
ZIP/Postal code 78054
Country Germany
 
Platforms (1)
GPL6885 Illumina MouseRef-8 v2.0 expression beadchip
Samples (16)
GSM5111567 SHAM 3 days 1
GSM5111568 PCI 3 days 1
GSM5111569 SHAM 10 weeks 4
Relations
BioProject PRJNA705148

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
GSE167610_RAW.tar 22.0 Mb (http)(custom) TAR (of IDAT)
GSE167610_non_normalized.txt.gz 4.8 Mb (ftp)(http) TXT
Raw data provided as supplementary file
Processed data included within Sample table
Raw data are available on Series record

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