TY - JOUR
T1 - Rosiglitazone reversal of Tg2576 cognitive deficits is independent of peripheral gluco-regulatory status
AU - Rodriguez-Rivera, Jennifer
AU - Denner, Larry
AU - Dineley, Kelly T.
N1 - Funding Information:
This work was supported by the National Institutes of Health under Ruth L. Kirschstein National Research Service Award ( F31 NS052928 ) (J.R.R), NIH grant R01- AG031859 , the Mitchell Center for Neurodegenerative Diseases , and the Sealy Foundation (K.T.D). Authors have disclosed no actual or potential conflicts of interest. We thank Dr. Dale Hogan, Mrs. Wanda Lejeune, and Dr. Wei Song for technical assistance, and Dr. Caterina M. Hernandez for editing assistance.
PY - 2011/1/1
Y1 - 2011/1/1
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Fear conditioning
KW - Glucose tolerance test
KW - Hippocampus-dependent learning and memory
KW - Insulin
KW - Mouse model
KW - PPARγ
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U2 - 10.1016/j.bbr.2010.08.002
DO - 10.1016/j.bbr.2010.08.002
M3 - Article
C2 - 20709114
AN - SCOPUS:78149407291
VL - 216
SP - 255
EP - 261
JO - Behavioural Brain Research
JF - Behavioural Brain Research
SN - 0166-4328
IS - 1
ER -