Rosiglitazone reversal of Tg2576 cognitive deficits is independent of peripheral gluco-regulatory status.
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.
Rodriguez-Rivera
Jennifer
J
Department of Neurology, University of Texas Medical Branch, Galveston, TX 77555, United States.
Denner
Larry
L
Dineley
Kelly T
KT
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D019540:Area Under Curve; D001245:Association Learning / Q000187:drug effects*; D001786:Blood Glucose / Q000378:metabolism*; D003071:Cognition / Q000187:drug effects*; D004195:Disease Models, Animal; D006946:Hyperinsulinism / Q000235:genetics / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D008568:Memory / Q000187:drug effects*; D051379:Mice; D008822:Mice, Transgenic; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D045162:Thiazolidinediones; D000077154:Rosiglitazone