1 Sanders-Brown Center on Aging, University of Kentucky, Lexington KY, USA.
2 Department of Epidemiology, University of Kentucky, Lexington KY, USA.
ASN Neuro. 2019 Jan-Dec;11:1759091419865788. doi: 10.1177/1759091419865788.
Elevated homocysteine in the blood, or hyperhomocysteinemia, is a recognized risk factor for multiple causes of dementia including Alzheimer’s disease. While reduction of homocysteine levels can generally be accomplished in a straightforward manner, the evidence regarding the cognitive benefits of this approach is less clear. To identify adjunct therapeutic targets that might more effectively restore cognition, the present series of experiments characterizes early and later cerebrovascular changes in a model of hyperhomocysteinemia. Sex-balanced groups of adult C57BL/6J mice were administered a diet deficient in vitamins B, B, and B (folate) and supplemented with excess methionine. They were subsequently assessed for changes in cerebral blood flow, memory, blood–brain barrier permeability, and selected vascular-associated genes. Blood flow deficits and barrier permeability changes occurred alongside changes in memory and in genes associated with metabolism, endothelial nitric oxide signaling, barrier integrity, and extracellular matrix remodeling. Significant sexually dimorphic responses to the diet were also detected. Taken together, these data deepen our understanding of a major contributor to dementia burden.
血液中同型半胱氨酸水平升高，即高同型半胱氨酸血症，是多种痴呆症（包括阿尔茨海默病）的公认危险因素。虽然通常可以通过简单的方法降低同型半胱氨酸水平，但这种方法对认知益处的证据并不明确。为了确定更有效的认知恢复辅助治疗靶点，本系列实验描述了高同型半胱氨酸血症模型中早期和晚期脑血管变化。均衡性别比例的成年 C57BL/6J 小鼠接受缺乏维生素 B₁₂、叶酸和维生素 B₆（B 族维生素）的饮食，并补充过量蛋氨酸。随后评估它们的大脑血流、记忆、血脑屏障通透性和选定的血管相关基因的变化。血流不足和屏障通透性变化伴随着记忆变化以及与代谢、内皮一氧化氮信号转导、屏障完整性和细胞外基质重塑相关的基因变化。还检测到了对饮食的显著性别二态反应。总的来说，这些数据加深了我们对痴呆症负担的一个主要因素的理解。
