Anti-inflammatory treatment in AD mice protects against neuronal pathology.
Anti-inflammatory treatment in AD mice protects against neuronal pathology.
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DOI：
10.1016/j.expneurol.2009.07.032
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发表时间：
2010-06
影响因子：
5.3
通讯作者：
Dedeoglu, Alpaslan
中科院分区：
文献类型：
--
作者：
Choi, Ji-Kyung;Jenkins, Bruce G.;Carreras, Isabel;Kaymakcalan, Sukru;Cormier, Kerry;Kowall, Neil W.;Dedeoglu, Alpaslan
关键词：
先前的研究表明，非甾体抗炎药（NSAID）可能会降低阿尔茨海默病（AD）的发病率，并延迟AD小鼠模型的症状发作或减缓症状进展。我们研究了慢性NSAID治疗的效果，以确定哪些病理特征可能得到改善。我们通过测量淀粉样蛋白斑块沉积、Aβ肽水平和磁共振波谱（MRS）神经化学特征，比较了NSAID布洛芬和塞来昔布对两个不同年龄APPxPS 1小鼠免疫组织学和神经化学标志物的影响。在6个月龄时，使用MRS，在PSAPP小鼠和WT小鼠之间观察到很少的神经化学变化。伊曲康而不是塞来昔布治疗显著降低了6个月时额叶皮质中的Aβ42/40比值，但总体淀粉样斑块负荷不变。与先前在小鼠模型中的发现一致，与WT相比，在17月龄时，AD小鼠中神经元标记物NAA和谷氨酸减少，星形胶质细胞标记物谷氨酰胺和肌醇增加。吲哚美辛对NAA和谷氨酸的损失提供了显着的保护。这两种药物都没有显著影响肌醇或谷氨酰胺水平。伊立替康和塞来昔布均降低了斑块负荷，对Aβ1-42水平无显著影响。NAA水平与菌斑负荷显著相关。这些结果表明，选择性NSAID（布洛芬和可能的塞来昔布）治疗可以防止神经元病理。
Prior studies suggest that non-steroidal anti-inflammatory drugs (NSAIDs) may lower the incidence of Alzheimer’s disease (AD) and delay onset or slow progression of symptoms in mouse models of AD. We examined the effects of chronic NSAID treatment in order to determine which elements of the pathological features might be ameliorated. We compared the effects of the NSAIDs ibuprofen and celecoxib on immunohistological and neurochemical markers at two different ages in APPxPS1 mice using measurements of amyloid plaque deposition, Aβ peptide levels and neurochemical profiles using magnetic resonance spectroscopy (MRS). At six months of age, few neurochemical changes were observed between PSAPP mice and WT mice using MRS. Ibuprofen, but not celecoxib, treatment significantly decreased the Aβ42/40 ratio in frontal cortex at six months, but overall amyloid plaque burden was unchanged. Consistent with prior findings in mouse models, at 17 months of age there was a decrease in the neuronal markers NAA and glutamate, and an increase in the astrocytic markers glutamine and myo-inositol in AD mice compared to WT. Ibuprofen provided significant protection against NAA and glutamate loss. Neither of the drugs significantly affected myo-inositol or glutamine levels. Both Ibuprofen and celecoxib lowered plaque burden without a significant effect on Aβ1–42 levels. NAA levels significantly correlated with plaque burden. These results suggest that selective NSAIDs (ibuprofen and possibly celecoxib) treatment can protect against the neuronal pathology.
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影响因子：
158.5
作者：
in 't Veld, BA;Ruitenberg, A;Stricker, BHC
通讯作者：
Stricker, BHC
影响因子：
64.8
作者：
Weggen, S;Eriksen, JL;Koo, EH
通讯作者：
Koo, EH
影响因子：
19.7
作者：
SHONK, TK;MOATS, RA;ROSS, BD
通讯作者：
ROSS, BD
影响因子：
4.7
作者：
URENJAK, J;WILLIAMS, SR;NOBLE, M
通讯作者：
NOBLE, M
影响因子：
2.9
作者：
BRAND, A;RICHTERLANDSBERG, C;LEIBFRITZ, D
通讯作者：
LEIBFRITZ, D