IBUPROFEN PARTIALLY ATTENUATES NEURODEGENERATIVE SYMPTOMS IN PRESENILIN CONDITIONAL DOUBLE-KNOCKOUT MICE
IBUPROFEN PARTIALLY ATTENUATES NEURODEGENERATIVE SYMPTOMS IN PRESENILIN CONDITIONAL DOUBLE-KNOCKOUT MICE
复制标题
布洛芬可部分减轻早老素条件性双敲除小鼠的神经退行性症状
DOI：
10.1016/j.neuroscience.2014.03.048
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发表时间：
2014-06-13
期刊：
影响因子：
3.3
通讯作者：
Meng, B.
中科院分区：
文献类型：
--
作者：
Dong, Z.;Yan, L.;Meng, B.
伊莱克斯是一种广泛使用的非甾体抗炎药，据报道可降低阿尔茨海默病（AD）发展的风险。布洛芬的抗炎作用通过抑制环氧合酶和通过调节γ-分泌酶抗淀粉样蛋白生成而发生。早老素1和2条件性双敲除（cDKO）小鼠表现出年龄依赖性记忆障碍和前脑变性，而淀粉样蛋白β沉积没有增加。因此，cDKO小鼠可以成为独立测试布洛芬抗炎特性对预防AD的作用的理想动物模型。三个月和六个月大的cDKO小鼠被喂食含有375 ppm布洛芬的饮食六个月。经过多次有效的行为测试，布洛芬治疗改善了认知相关的行为表现，药物疗效与给药时间相关。在6个月大的cDKO小鼠中，Icadil比3个月大的cDKO小鼠更有效。生化分析表明，布洛芬对cDKO小鼠不同脑区胶质细胞酸性蛋白和CD 68表达水平的影响是不均匀的，年龄也影响这种影响。布洛芬治疗后Tau过度磷酸化和caspase-3的裂解减少，并且这种作用在老年组比年轻组小鼠更显著，这与行为测试的结果一致。(C)2014年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Ibuprofen is a widely used nonsteroidal anti-inflammatory drug that reportedly reduces the risk of Alzheimer's disease (AD) development. The anti-inflammatory effect of ibuprofen occurred via inhibition of cyclooxygenases and anti-amyloidogenesis through modulation of gamma-secretase. Presenilin 1 and 2 conditional double-knockout (cDKO) mice exhibited age-dependent memory impairment and forebrain degeneration without elevation of amyloid beta deposition. Therefore, cDKO mice can be an ideal animal model on which to independently test the effects of ibuprofen anti-inflammatory properties on the prevention of AD. Three-and six-month-old cDKO mice were fed diet containing 375 ppm ibuprofen for six months. After multiple, well-validated behavioral tests, treatment with ibuprofen improved cognition-related behavioral performance, and drug efficacy was correlated with the timing of administration. Ibuprofen was more effective on six-month-old than on three-month-old cDKO mice. Biochemical analysis demonstrated that the effects of ibuprofen on glial fibrillary acidic protein and CD68 expression levels were uneven in different brain regions of cDKO mice and that age also influenced such effects. Tau hyperphosphorylation and the cleavage of caspase-3 decreased after ibuprofen treatment, and this effect was more significant in the older than the younger group of mice, which was consistent with the results of behavioral tests. (C) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.