Rosiglitazone reversal of Tg2576 cognitive deficits is independent of peripheral gluco-regulatory status.
Rosiglitazone reversal of Tg2576 cognitive deficits is independent of peripheral gluco-regulatory status.
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DOI：
10.1016/j.bbr.2010.08.002
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发表时间：
2011-01-01
影响因子：
2.7
通讯作者：
Dineley, Kelly T.
中科院分区：
文献类型：
--
作者：
Rodriguez-Rivera, Jennifer;Denner, Larry;Dineley, Kelly T.
关键词：
越来越多的证据表明，葡萄糖调节异常和过氧化物酶体增殖物激活受体（PPAR）γ功能与阿尔茨海默病（AD）风险增加有关。在这项研究中，我们使用Tg 2576 AD小鼠模型来检验这一假设，即罗格列酮（RTZ）一个月后的PPAR γ激动剂的认知改善与外周血糖调节状态相关。我们评估了Tg 2576小鼠在外周葡萄糖调节异常发生之前、同时或之后（分别为4、8和12月龄）接受RTZ治疗1个月后的认知和外周葡萄糖调节状态。而5个月大（MO）和13 MO Tg 2576在用RTZ治疗一个月后没有获得认知改善，9 MO Tg 2576小鼠表现出联合学习和记忆缺陷的逆转。RTZ治疗后，9和13 MO Tg 2576小鼠的外周血糖调节异常得到改善; RTZ治疗对5 MO Tg 2576小鼠的正常血糖状态无影响。这些发现表明RTZ介导的认知改善与外周葡萄糖调节异常本身无关，但反映了该小鼠模型中认知下降的年龄依赖性机制差异。
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 one-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 one-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 one-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.
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影响因子：
7.7
作者：
Baura, GD;Foster, DM;Schwartz, MW
通讯作者：
Schwartz, MW
影响因子：
5.3
作者：
Pedersen, Ward A.;McMillan, Pamela J.;Haynatzki, Gleb R.
通讯作者：
Haynatzki, Gleb R.
影响因子：
4.1
作者：
Craft, S;Asthana, S;Grimwood, K
通讯作者：
Grimwood, K
DOI：
10.1007/s004060050101
发表时间：
1999-12-01
影响因子：
4.7
作者：
Förstl, H;Kurz, A
通讯作者：
Kurz, A
影响因子：
25
作者：
Chapman, PF;White, GL;Hsiao, KK
通讯作者：
Hsiao, KK