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Series GSE20219 Query DataSets for GSE20219
Status Public on May 05, 2010
Title Effects of Long-term Pioglitazone Treatment on Peripheral and Central Markers of Aging
Organism Rattus norvegicus
Experiment type Expression profiling by array
Summary Background: Thiazolidinediones (TZDs) activate peroxisome proliferator-activated receptor gamma (PPARgamma) and are used clinically to help restore peripheral insulin sensitivity in Type 2 diabetes (T2DM). Interestingly, long-term treatment of mouse models of Alzheimer’s disease (AD) with TZDs also has been shown to reduce several well-established brain biomarkers of AD including inflammation, oxidative stress and Abeta accumulation. While some of the TZD actions are becoming clear in AD models and may mediate their reported beneficial impact in AD patients, little is known about the functional consequences of TZDs in animal models of normal aging. Because aging is a common risk factor for both AD and T2DM, we investigated whether the TZD, pioglitazone could alter brain aging under non-pathological conditions. Findings: The TZD pioglitazone (PIO) was incorporated into the diet to yield a final dose of approximately 2.3 mg/kg body weight/day. PIO reduced insulin levels irrespective of age. Interestingly, a significant reduction in the Ca2+-dependent afterhyperpolarization was seen in the aged animals with no significant change in LTP maintenance or learning and memory performance. Finally, a combination of microarray analyses on hippocampal tissue and serum-based multiplex cytokine assays revealed that age-dependent inflammatory changes in brain and periphery were not reversed by PIO.
Conclusions: While current research efforts continue to address the underlying processes responsible for the progressive decline in cognitive function seen during aging, available medical treatments are still very limited. Our study, therefore, was aimed at elucidating potentially novel actions of TZDs in the aging brain. Using a clinically-relevant dose and delivery method, PIO had no detectable impact on several indices of brain aging and failed to alter both peripheral and central age-related increases in inflammatory signaling.

Keywords: hippocampus, rat, young or aged, control or pioglitazone-treated
 
Overall design We used the F344 rat model of aging, and monitored behavioral, electrophysiological, and molecular variables to assess the effects of pioglitazone (PIO-Actos(R) a TZD) on several hippocampal biomarkers of aging associated with learning deficits. Starting at 3 months or 17 months of age, male rats were treated for 4-5 months with either a control or a PIO-containing diet. PIO was incorporated into the diet to yield a final dose of approximately 2.3 mg/kg body weight/day.
 
Contributor(s) Blalock EM, Phelps JT, Pancani T, Searcy JL, Anderson K, Gant JC, Popovic J, Avdiushko M, Cohen DA, Chen K, Porter NM, Thibault O
Citation(s) 20454453
Submission date Feb 07, 2010
Last update date Jul 31, 2017
Contact name Eric M Blalock
E-mail(s) eric.blalock@uky.edu
Phone 859-323-8033
Organization name University of Kentucky
Department Molecular and Biomedical Pharmacology
Lab Blalock
Street address 800 Rose St.
City Lexington
State/province KY
ZIP/Postal code 40475
Country USA
 
Platforms (1)
GPL1355 [Rat230_2] Affymetrix Rat Genome 230 2.0 Array
Samples (29)
GSM506974 rat hippocampus (combined dorsal and ventral aspects), young control, subject 1
GSM506975 rat hippocampus (combined dorsal and ventral aspects), young control, subject 2
GSM506976 rat hippocampus (combined dorsal and ventral aspects), young control, subject 3
Relations
BioProject PRJNA124145

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Supplementary file Size Download File type/resource
GSE20219_RAW.tar 80.9 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table
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