Prevention of amyloid β-induced memory impairment by fluvastatin, associated with the decrease in amyloid β accumulation and oxidative stressin amyloid β injection mouse model
Prevention of amyloid β-induced memory impairment by fluvastatin, associated with the decrease in amyloid β accumulation and oxidative stressin amyloid β injection mouse model
复制标题
DOI：
10.3892/ijmm.21.5.531
复制
发表时间：
2008-05
影响因子：
5.4
通讯作者：
H. Kurinami;N. Sato;M. Shinohara;Daisuke Takeuchi;S. Takeda;M. Shimamura;T. Ogihara;R. Morishita
中科院分区：
文献类型：
--
作者：
H. Kurinami;N. Sato;M. Shinohara;Daisuke Takeuchi;S. Takeda;M. Shimamura;T. Ogihara;R. Morishita
阿尔茨海默病（AD）是老年人痴呆的最常见原因，其特征在于含有淀粉样蛋白β（Abeta）的斑块和神经元缠结，以及突触和神经元损失，沿着进行性认知损害。虽然越来越多的证据表明3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂（他汀类药物）对AD的有益作用，但这一观点仍有争议。为了评估他汀类药物对Abeta诱导的认知障碍的疗效，我们采用了Abeta注射模型。使用这个模型，本研究表明，氟伐他汀预处理，但不是后处理后，就在Abeta暴露，防止Abeta诱导的记忆障碍。我们还观察到，氟伐他汀显着降低Abeta的积累和氧化应激后Abeta注射。用辛伐他汀而不是氟伐他汀治疗的小鼠没有表现出对Abeta诱导的记忆障碍的预防，并且没有表现出氧化应激的显著降低。更重要的是，氟伐他汀显著防止了由Abeta诱导的基底前脑神经元的损失。总体而言，本研究表明，氟伐他汀显着预防记忆障碍诱导的Abeta。氟伐他汀的有益作用可能是通过显著降低Abeta积累和氧化应激来保护神经元。在临床实践中，开始氟伐他汀治疗的时间可能是实现对认知功能的有益影响的关键。
Alzheimer's disease (AD), the most common cause of dementia in the elderly, is characterized by amyloid beta (Abeta)-containing plaques and neurofibrillary tangles, and synaptic and neuronal loss, along with progressive cognitive impairment. Although growing evidence suggests the beneficial effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) on AD, this notion is still controversial. To evaluate the efficacy of statins for Abeta-induced cognitive impairment, we employed an Abeta injection model. Using this model, the present study demonstrated that pretreatment with fluvastatin, but not post-treatment just after Abeta exposure, prevented Abeta-induced memory impairment. We also observed that fluvastatin significantly decreased Abeta accumulation and oxidative stress after Abeta injection. Mice treated with simvastatin, but not fluvastatin, did not demonstrate the prevention of Abeta-induced memory impairment, and showed no significant decrease in oxidative stress. More importantly, fluvastatin significantly prevented the loss of neurons in the basal forebrain induced by Abeta. Overall, the present study demonstrated that fluvastatin significantly prevented memory impairment induced by Abeta. The beneficial effects of fluvastatin might be explained by the preservation of neurons through a significant decrease in Abeta accumulation and oxidative stress. In clinical practice, the timing of the start of fluvastatin treatment might be critical in achieving a beneficial effect on cognitive function.