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

Jennifer Rodriguez-Rivera, Larry Denner, Kelly T. Dineley

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

Converging lines of evidence associate gluco-regulatory abnormalities and peroxisome-proliferator-activated receptor (PPAR) gamma function with increased risk for Alzheimer's disease (AD). In this study, we used the Tg2576 AD mouse model to test the hypothesis that cognitive improvement following 1 month of PPAR gamma agonism with rosiglitazone (RTZ) correlates with peripheral gluco-regulatory status. We assessed cognition and peripheral gluco-regulatory status of Tg2576 mice following 1 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 1 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 gluco-regulatory abnormalities per se, but reflects the age-dependent mechanistic differences that underlie cognitive decline in this mouse model.

Original languageEnglish (US)
Pages (from-to)255-261
Number of pages7
JournalBehavioural Brain Research
Volume216
Issue number1
DOIs
StatePublished - Jan 1 2011

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Keywords

  • Alzheimer's disease
  • Fear conditioning
  • Glucose tolerance test
  • Hippocampus-dependent learning and memory
  • Insulin
  • Mouse model
  • PPARγ

ASJC Scopus subject areas

  • Behavioral Neuroscience

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