Vascular endothelial growth factor alleviates mitochondrial dysfunction and suppression of mitochondrial biogenesis in models of Alzheimer's disease
Vascular endothelial growth factor alleviates mitochondrial dysfunction and suppression of mitochondrial biogenesis in models of Alzheimer's disease
复制标题
血管内皮生长因子减轻阿尔茨海默病模型中的线粒体功能障碍并抑制线粒体生物发生
DOI：
10.1080/00207454.2020.1733564
复制
发表时间：
2020-03-04
影响因子：
2.2
通讯作者：
Wang, Ping
中科院分区：
文献类型：
--
作者：
Liu, Xiangtian;Chu, Bingcong;Wang, Ping
目的：线粒体功能障碍是阿尔茨海默病(AD)的一个显著特征。鉴于血管内皮生长因子(VEGF)在AD模型中具有保护作用，本研究旨在探讨血管内皮生长因子对AD模型线粒体功能的影响。材料和方法：将腺相关病毒(AAV)-血管内皮生长因子(VEGF)注射到APP/PS1小鼠的海马区。使用Morris水迷宫(MWM)评估这些小鼠的认知功能，并测量海马区的β-淀粉样蛋白(Aβ)水平。以Aβ(25-35)作为AD细胞模型，测定SH-SY5Y细胞经Aβ(25-35)处理后的细胞活力和活性氧(ROS)水平。用透射电子显微镜观察线粒体结构的变化，并记录线粒体DNA(MtDNA)拷贝数和线粒体膜电位。最后，我们研究了血管内皮生长因子对线粒体生物发生、自噬和线粒体自噬(有丝分裂吞噬)的影响，这在体内和体外都是用免疫印迹法检测的。结果：经血管内皮生长因子治疗后，小鼠的空间学习和记忆能力得到改善，Aβ水平降低。血管内皮生长因子保护SH-SY5Y细胞免受Aβ(25-35)诱导的神经毒性，表现为细胞活力增加和ROS产生减少。与这些效应相关的是线粒体结构和功能的改善，以及由于刺激线粒体生物发生而导致的线粒体数量的增加。结论：血管内皮生长因子可减轻AD模型中Aβ相关的病理改变。在一定程度上，血管内皮生长因子的这些有益作用源于对线粒体的保护和刺激线粒体的生物发生。
Purpose: Mitochondrial dysfunction is a prominent feature of Alzheimer's disease (AD). As vascular endothelial growth factor (VEGF) has been shown to be protective in AD, the aim of this study was to investigate the effects of VEGF on mitochondrial function in models of AD. Materials and methods: Adeno associated virus (AAV)-VEGF was injected into the hippocampus of APP/PS1 mice. Cognitive function was assessed in these mice with use of the Morris water maze (MWM) and beta-amyloid (A beta) levels in the hippocampus were also measured. Cell viability and reactive oxygen species (ROS) levels were determined in the SH-SY5Y cells treated with A beta(25-35) which served as a cell model of AD. Transmission electron microscopy (TEM) was used to evaluate structural changes in mitochondria and mitochondrial DNA (mtDNA) copy number and mitochondrial membrane potential (MMP) were also recorded. Finally, we investigated the effects of VEGF upon mitochondrial biogenesis, autophagy and mitochondrial autophagy (mitophagy) as determined both in vivo and in vitro with western blots. Results: VEGF treated mice showed improvements in spatial learning and memory along with reduced A beta levels. VEGF protected SH-SY5Y cells against A beta(25-35) induced neurotoxicity as demonstrated by increased cell viability and decreased ROS production. Associated with these effects were improvements in mitochondrial structure and function, and increased numbers of mitochondria resulting from stimulation of mitochondrial biogenesis. Conclusions: VEGF alleviates A beta related patholoy in models of AD. In part, these beneficial effects of VEGF result from protection of mitochondria and stimulation of mitochondrial biogenesis.