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 language | English (US) |
|---|---|
| Pages (from-to) | 255-261 |
| Number of pages | 7 |
| Journal | Behavioural Brain Research |
| Volume | 216 |
| Issue number | 1 |
| DOIs | |
| State | Published - 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
Cite this
Rosiglitazone reversal of Tg2576 cognitive deficits is independent of peripheral gluco-regulatory status. / Rodriguez-Rivera, Jennifer; Denner, Larry; Dineley, Kelly.
In: Behavioural Brain Research, Vol. 216, No. 1, 01.01.2011, p. 255-261.Research output: Contribution to journal › Article
}
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
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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UR - http://www.scopus.com/inward/citedby.url?scp=78149407291&partnerID=8YFLogxK
U2 - 10.1016/j.bbr.2010.08.002
DO - 10.1016/j.bbr.2010.08.002
M3 - Article
VL - 216
SP - 255
EP - 261
JO - Behavioural Brain Research
JF - Behavioural Brain Research
SN - 0166-4328
IS - 1
ER -