Ligustilide Ameliorates Memory Deficiency in APP/PS1 Transgenic Mice via Restoring Mitochondrial Dysfunction.
Ligustilide Ameliorates Memory Deficiency in APP/PS1 Transgenic Mice via Restoring Mitochondrial Dysfunction.
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藁本内酯通过恢复线粒体功能改善 APP/PS1 转基因小鼠的记忆缺陷
DOI：
10.1155/2018/4606752
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发表时间：
2018
影响因子：
--
通讯作者：
Zhang YB
中科院分区：
文献类型：
--
作者：
Xu YJ;Mei Y;Qu ZL;Zhang SJ;Zhao W;Fang JS;Wu J;Yang C;Liu SJ;Fang YQ;Wang Q;Zhang YB
当归的主要亲脂成分当归内酯已被证明可以改善一些阿尔茨海默病小鼠模型的认知功能障碍，但其机制尚不完全清楚。在这项研究中，我们使用7个月大的APP/PS1小鼠来探索LIG是否能够防止阿尔茨海默病的进展。Morris水迷宫和Y迷宫实验结果表明，每天灌胃给予LIG(10 mg/kg、40 mg/kg)8周可改善APP/PS1小鼠的记忆障碍。硫代黄素-S染色和免疫印迹结果(Aβ1-42单体/寡体、APP、ADAM10、SAPα和PREP)表明，LIG降低了APP/PS1小鼠脑组织中Aβ的水平。透射电子显微镜分析显示，LIG使APP/PS1小鼠海马CA1区线粒体数量减少，线粒体长度增加。在用LIG处理的APP/PS1小鼠中，发现DRp1(分裂)水平降低，Mfn1、Mfn2和OPA1水平升高(融合)。LIG可提高脑内ATP水平，增加线粒体细胞色素c氧化酶(CCO)和琥珀酸脱氢酶(SDH)活性，从而减轻线粒体功能障碍。LIG通过降低脑组织中丙二醛(MDA)和活性氧(ROS)水平，提高Mn-SOD活性而发挥抗氧化作用。海马和皮质中PSD-95、突触素和突触素1水平的升高表明LIG提供了突触保护。这些结果表明，LIG治疗可以改善APP/PS1小鼠的线粒体动力学和形态问题，改善线粒体功能，降低脑内Aβ水平，恢复突触结构，改善记忆障碍。这些结果提示LIG可能是一种潜在的抗痴呆药物。
Ligustilide, the main lipophilic component of Radix angelicae sinensis, has been shown to ameliorate cognitive dysfunction in a few Alzheimer's disease mouse models, but its mechanism is not fully understood. In this study, we employed 7-month-old APP/PS1 mice to explore whether LIG is able to protect against Alzheimer's disease progression. The Morris water maze and Y-maze test results showed that eight weeks of intragastric administration of LIG (10 mg/kg, 40 mg/kg) every day improved memory deficit in APP/PS1 mice. The thioflavin-S staining and Western blot results (Aβ1-42 monomer/oligomer, APP, ADAM10, SAPPα, and PreP) showed that LIG reduced Aβ levels in the brain of APP/PS1 mice. Transmission electron microscopy analysis showed that LIG reduced the mitochondria number and increased the mitochondrial length in the hippocampal CA1 area of APP/PS1 mice. A reduced level of Drp1 (fission) and increased levels of Mfn1, Mfn2, and Opa1 (fusion) were found in APP/PS1 mice treated with LIG. An increased ATP level in the brain and increased activities of cytochrome c oxidase (CCO) and succinate dehydrogenase (SDH) in mitochondrion separated from the hippocampus and cortex revealed that LIG alleviated mitochondrial dysfunction. LIG exerts an antioxidation effect via reducing the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) and increasing the activity of Mn-SOD in the brain. Elevated levels of PSD-95, synaptophysin, and synapsin 1 in both the hippocampus and cortex indicated that LIG provided synaptic protection. These findings show that treatment with LIG ameliorates mitochondrial dynamics and morphology issues, improves mitochondrial function, reduces Aβ levels in the brain, restores the synaptic structure, and ameliorates memory deficit in APP/PS1 mice. These results imply that LIG may serve as a potential antidementia drug.
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DOI：
10.3233/jad-2011-101716
发表时间：
2011
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Alikhani N;Guo L;Yan S;Du H;Pinho CM;Chen JX;Glaser E;Yan SS
通讯作者：
Yan SS
影响因子：
--
作者：
Cai H;Wang Y;He J;Cai T;Wu J;Fang J;Zhang R;Guo Z;Guan L;Zhan Q;Lin L;Xiao Y;Pan H;Wang Q
通讯作者：
Wang Q
DOI：
10.1083/jcb.200211046
发表时间：
2003-01-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Chen H;Detmer SA;Ewald AJ;Griffin EE;Fraser SE;Chan DC
通讯作者：
Chan DC
影响因子：
3.4
作者：
Cheng, Li-Ling;Chen, Xi-Nan;Du, Jun-Rong
通讯作者：
Du, Jun-Rong
影响因子：
6.1
作者：
Garcia-Alloza, Monica;Robbins, Elissa M.;Frosch, Matthew P.
通讯作者：
Frosch, Matthew P.