Atorvastatin and pitavastatin improve cognitive function and reduce senile plaque and phosphorylated tau in aged APP mice
Atorvastatin and pitavastatin improve cognitive function and reduce senile plaque and phosphorylated tau in aged APP mice
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DOI：
10.1016/j.brainres.2010.11.067
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发表时间：
2011-01-31
期刊：
影响因子：
2.9
通讯作者：
Abe, Koji
中科院分区：
文献类型：
--
作者：
Kurata, Tomoko;Miyazaki, Kazunori;Abe, Koji
除了简单地降低血清胆固醇水平外，3-羟基-3-甲基戊二酰辅酶A （HMG-CoA）还原酶抑制剂（他汀类药物）具有多种多营养作用，如减少氧化应激、神经炎症和神经毒性。然而，这种多营养效应尚未在一种新的他汀类药物（匹伐他汀）中得到充分研究。我们检查并比较了两种强效他汀类药物(阿托伐他汀，30 mg/kg/天，口服；pitavastatin, 3 mg/kg/d, p.o.)对5月龄至20 M的淀粉样前体蛋白（APP）转基因（Tg）小鼠血清脂质水平、认知功能障碍、老年斑（SP）和磷酸化tau阳性营养不良性神经炎（p tau DN）的影响。这两种他汀类药物在15和20 M时改善行为记忆，降低SP和p tau DN的数量，而不影响血脂水平。他汀类药物的保护作用从治疗开始到现在的模型小鼠需要10 M才能显示出改善，他汀类药物治疗的敏感性与行为记忆、SP和p tau DN依次相关。这些发现表明，早期使用阿托伐他汀和匹伐他汀治疗可防止认知功能和淀粉样变过程的恶化，这可能是由于多营养效应，这表明阿托伐他汀和匹伐他汀具有治疗阿尔茨海默病（AD）的潜力。(C) 2010 Elsevier B.V.版权所有
In addition to simply reducing the serum level of cholesterol, 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have various pleiotrophic effects such as reducing oxidative stress, neuroinflammation, and neurotoxicity. However, such a pleiotrophic effect has not been fully studied in a new statin (pitavastatin). we examined and compared the effects of two strong statins (atorvastatin, 30 mg/kg/day, p.o.; pitavastatin, 3 mg/kg/day, p.o.) on the serum level of lipids, cognitive dysfunction, senile plaque (SP) and phosphorylated tau-positive dystrophic neuritis (p tau DN) in amyloid precursor protein (APP) transgenic (Tg) mice from 5 months (M) of age to 20 M. These two statins improved behavioral memory and reduced the numbers of SP and p tau DN at 15 and 20 M without affecting serum lipid levels, but preserved mice brain weight in pitavastatin group at 20 M. These protective effects of statins took 10 M from the beginning of treatment to show an improvement in the present model mice, and sensitivity to the statin treatment was linked to behavioral memory, SP and p tau DN in this order. These findings suggest that early treatment with both atorvastatin and pitavastatin prevented subsequent worsening of cognitive function and the amyloidogenic process, probably due to pleiotrophic effects, suggesting a therapeutic potential for Alzheimer's disease (AD). (C) 2010 Elsevier B.V. All rights reserved.