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Series GSE220971 Query DataSets for GSE220971
Status Public on Jun 07, 2023
Title Effect of Peripheral Cellular Senescence on Brain Aging and Cognitive Decline
Organism Rattus norvegicus
Experiment type Expression profiling by high throughput sequencing
Summary We test the idea that peripheral cellular senescence is a major driver of age-related cognitive impairment, such that treatment with the brain impermeable senolytic, ABT-263, can preserve cognition and markers of brain aging thought to underlie cognitive decline. Male F344 rats were treated from 12-18 months of age with quercetin + dasatinib or ABT-263 or vehicle and were compared to young (6 month). Senolytic treatments had similar effects in decreasing peripheral markers of senescence and the senescence-associated secretory phenotype (SASP), including plasma levels of several cytokines, rescued memory and hippocampal synaptic transmission, and decreased expression of immune response genes in the dentate gyrus (DG). Across senolytic treatment groups, differential DG gene expression was observed for cellular senescence and pathways linked to senescence, including negative regulation of cell death, ribosomes, and microglial activation consistent with differential access of dasatinib and ABT-263 to the brain. Finally, both senolytic treatments preserved the blood-brain barrier suggesting that leakage of clinically significant amounts of ABT-263 into the brain is unlikely. The results indicate that preserved cognition was due to removal of peripheral senescent cells, decreasing systemic inflammation that normally drives neuroinflammation, BBB breakdown, and impaired synaptic function.
 
Overall design Transcriptional profiles were analyzed in the DG sub-region of hippocampus from rats belonging to various groups: young (YNG, n = 10), aged vehicle (AV, n = 12), Aged + DQ (ADQ, n = 11), Aged + ABT-263 (AA, n = 11) treated rats.
 
Contributor(s) Budamagunta V, Foster TC, Kumar A, Rani A, Bean L, Sindhu SM, Yang Y, Zhou D
Citation(s) 36959691
Submission date Dec 14, 2022
Last update date Jun 07, 2023
Contact name Thomas C Foster
E-mail(s) foster1@ufl.edu
Phone 3522735093
Organization name University of Florida
Department Neuroscience
Lab L2-132 (MBI), Building-59
Street address 1149 S Newell Dr.
City Gainesville
State/province FL
ZIP/Postal code 32610
Country USA
 
Platforms (1)
GPL32950 Ion GeneStudio S5 (Rattus norvegicus)
Samples (44)
GSM6833323 3890
GSM6833324 3983
GSM6833325 3984
Relations
BioProject PRJNA912188

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SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE220971_DG-Seq-Samples-Attributes-Corrected.csv.gz 299 b (ftp)(http) CSV
GSE220971_Normalized-Count-Corrected-12-9-22.csv.gz 3.9 Mb (ftp)(http) CSV
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