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Rosiglitazone reversal of Tg2576 cognitive deficits is independent of peripheral gluco-regulatory status


Year of Publication:
Contact PI Name:
Kelly T. Dineley
Contact PI Affiliation:
University of Texas Medical Branch Galveston, Texas, USA
Jennifer Rodriguez-Rivera, Larry Denner
Primary Reference (PubMED ID):
Funding Source:
NIH Ruth L Kirschstein National Research Service Award (NRSA)
The Mitchell Center for Neurodegenerative Disease
Sealy Clinical Research Foundation
National Institute on Aging (NIA)
National Institute of Neurological Disorders and Stroke (NINDS)
Study Goal and Principal Findings:

This study investigated effects of rosiglitazone (RTZ) on cognitive impairment and peripheral gluco-regulatory status in Tg2576 mice.  In recent years, epidemiological studies suggest that there is a link between peripheral gluco-regulatory abnormalities and AD. Patients who suffer from severe peripheral insulin resistance and hyperinsulinemia experienced in type 2 diabetes mellitus (T2DM), have an approximately 65% increased risk of developing AD. Given the converging evidence associating peripheral glucoregulatory abnormalities and cognitive function in AD, insulin-sensitizing drugs have been proposed as a possible treatment for AD. RTZ is a member of the class of insulin-sensitizing drugs called thiazolidinediones. RTZ increases insulin sensitivity by functioning as a ligand to activate the nuclear receptor PPARγ. This study assessed cognition and peripheral gluco-regulatory status of Tg2576 mice following one-month treatment with RTZ initiated prior to, coincident with, or after, the onset of peripheral gluco-regulatory abnormalities (4, 8, and 12-months of age, respectively). Whereas 5-months-old (MO) and 13 MO Tg2576 did not gain cognitive improvement after one-month treatment with RTZ, 9 MO Tg2576 mice exhibited reversal of associative learning and memory deficits. Peripheral gluco-regulatory abnormalities were improved in 9 and 13 MO Tg2576 with RTZ treatment; RTZ treatment had no effect on the normal glucose status of 5 MO Tg2576 mice. These findings suggest that RTZ-mediated cognitive improvement does not correlate with peripheral glucoregulatory abnormalities per se, but reflects the age-dependent mechanistic differences that underlie cognitive decline in this mouse model.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Small Molecule
Therapeutic Agent:
Therapeutic Target:
Peroxisome Proliferator-Activated Receptor gamma (PPAR gamma)

Animal Model

Model Information:
Model Type:
Strain/Genetic Background:
Model Type:
Strain/Genetic Background:

Experimental Design

Is the following information reported in the study?:
Power/Sample Size Calculation
Randomized into Groups
Blinded for Treatment
Blinded for Outcome Measures
Pharmacokinetic Measures
Pharmacodynamic Measures
Toxicology Measures
ADME Measures
Route of Delivery
Duration of Treatment
Frequency of Administration
Age of Animal at the Beginning of Treatment
Age of Animal at the End of Treatment
Sex as a Biological Variable
Study Balanced for Sex as a Biological Variable
Number of Premature Deaths
Number of Excluded Animals
Statistical Plan
Genetic Background
Inclusion/Exclusion Criteria Included
Conflict of Interest


Outcome Measured
Outcome Parameters
Fear Conditioning Response