...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Brain research >Covert strokes prior to Alzheimer's disease onset accelerate peri-lesional pathology but not cognitive deficits in an inducible APP mouse model
【24h】

Covert strokes prior to Alzheimer's disease onset accelerate peri-lesional pathology but not cognitive deficits in an inducible APP mouse model

机译：在阿尔茨海默病发病之前的封面笔画加速了围栏病理学，但在诱导型App鼠标模型中没有认知缺陷

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

It is estimated that up to 1 in 3 healthy middle-aged adults will have had a covert stroke during their lifetime. Furthermore, post-stroke, survivors are more than twice as likely to develop dementia. In the present study, we aimed to model the impact of focal subclinical ischemia prior to the onset of AD pathogenesis in a preclinical model. We utilized endothelin-1 to induce ischemia in an iducible transgenic mouse model of Alzheimer's disease, APPsi:tTA, allowing for temporal control of APP gene expression. We induced the focal subclinical ischemic events in the absence of APP expression, thus prior to AD onset. T2 structural magnetic resonance imaging confirmed the volume and location of focal subclinical ischemic lesions to the medial prefrontal cortex. Following recovery from surgery and 7 weeks of APP expression, we found that two subclinical ischemic lesions resulted in a significant localized increase in amyloid load and in microglial activation proximal to the lesion. However, no differences were found in astrogliosis. A battery of behaviour tests was conducted, in which no significant differences were detected in activities of daily living and cognitive function between stroked and sham cohorts. Overall, our results demonstrated that APP expression was the sole driving force behind behavioural deficits. In conclusion, our results suggest that a history of two subclinical strokes prior to AD onset does not worsen early disease trajectory in a mouse model.
机译：据估计，高达三分之一的健康中年人在一生中会有隐性中风。此外，中风后，幸存者患痴呆症的可能性是正常人的两倍多。在本研究中，我们的目的是在临床前模型中模拟AD发病前局灶性亚临床缺血的影响。我们利用内皮素-1诱导阿尔茨海默病转基因小鼠模型APPsi:tTA缺血，从而对APP基因表达进行时间控制。我们在缺乏APP表达的情况下诱发局灶性亚临床缺血事件，因此在AD发病之前。T2结构磁共振成像证实了内侧前额叶皮质局灶性亚临床缺血性病变的体积和位置。术后恢复和APP表达7周后，我们发现两个亚临床缺血性病变导致病变附近的淀粉样蛋白负荷和小胶质细胞激活显著局部增加。然而，在星形胶质细胞增生方面没有发现差异。进行了一系列行为测试，在这些测试中，中风组和假中风组在日常生活活动和认知功能方面没有发现显著差异。总的来说，我们的结果表明，应用程序表达是行为缺陷背后的唯一驱动力。总之，我们的结果表明，在AD发病前有两次亚临床中风史不会恶化小鼠模型的早期疾病轨迹。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号