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

Behav Brain Res. 2011 Jan 1;216(1):255-61. doi: 10.1016/j.bbr.2010.08.002. Epub 2010 Aug 13.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism
  • Analysis of Variance
  • Animals
  • Area Under Curve
  • Association Learning / drug effects*
  • Blood Glucose / metabolism*
  • Cognition / drug effects*
  • Disease Models, Animal
  • Hyperinsulinism / genetics
  • Hyperinsulinism / metabolism
  • Hypoglycemic Agents / therapeutic use
  • Insulin / blood
  • Memory / drug effects*
  • Mice
  • Mice, Transgenic
  • Rosiglitazone
  • Thiazolidinediones / therapeutic use*

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Thiazolidinediones
  • Rosiglitazone