Department of Pharmacology and Toxicology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA.
Department of Physiology, Medical College of Georgia, Augusta University, 1462 Laney Walker Blvd, Augusta, GA, 30912, USA.
Geroscience. 2023 Jun;45(3):1471-1490. doi: 10.1007/s11357-023-00773-x. Epub 2023 Mar 18.
Alzheimer's disease (AD) is a global healthcare crisis. The TgF344-AD rat is an AD model exhibiting age-dependent AD pathological hallmarks. We confirmed that AD rats developed cognitive deficits at 6 months without alteration of any other major biophysical parameters. We longitudinally characterized cerebral hemodynamics in AD rats at 3, 4, 6, and 14 months. The myogenic responses of the cerebral arteries and arterioles were impaired at 4 months of age in the AD rats. Consistent with the ex vivo results, the AD rat exhibited poor autoregulation of surface and deep cortical cerebral blood flow 2 months preceding cognitive decline. The dysfunction of cerebral hemodynamics in AD is exacerbated with age associated with reduced cerebral perfusion. Further, abolished cell contractility contributes to cerebral hemodynamics imbalance in AD. This may be attributed to enhanced ROS production, reduced mitochondrial respiration and ATP production, and disrupted actin cytoskeleton in cerebral vascular contractile cells.
阿尔茨海默病（AD）是一场全球性的医疗保健危机。TgF344-AD 大鼠是一种 AD 模型，具有与年龄相关的 AD 病理特征。我们证实，AD 大鼠在 6 个月时出现认知缺陷，而其他主要生物物理参数没有改变。我们在 3、4、6 和 14 个月时对 AD 大鼠的脑血流动力学进行了纵向特征描述。在 4 个月大时，AD 大鼠的脑动脉和小动脉的肌源性反应受损。与体外结果一致的是，AD 大鼠在认知能力下降前 2 个月就表现出表面和深层皮质脑血流的自动调节能力差。随着年龄的增长，AD 大鼠的脑血流动力学功能障碍加剧，与脑灌注减少有关。此外，细胞收缩功能的丧失导致 AD 中的脑血流动力学失衡。这可能归因于 ROS 产生增加、线粒体呼吸和 ATP 产生减少以及脑血管收缩细胞中的肌动蛋白细胞骨架破坏。
