High Dietary Advanced Glycation End Products Impair Mitochondrial and Cognitive Function.
High Dietary Advanced Glycation End Products Impair Mitochondrial and Cognitive Function.
复制标题
DOI：
10.3233/jad-191236
复制
发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Yan SS
中科院分区：
文献类型：
--
作者：
Akhter F;Chen D;Akhter A;Sosunov AA;Chen A;McKhann GM;Yan SF;Yan SS
晚期糖基化终末产物 (AGE) 是导致衰老和迟发性神经退行性疾病（包括阿尔茨海默病）认知能力下降的重要危险因素。然而，饮食中的 AGEs 是否以及如何加剧衰老过程中的认知障碍和脑线粒体功能障碍仍然很大程度上未知。我们研究了膳食 AGEs 对小鼠 AGE 加合物积累、线粒体功能和认知表现的直接影响。给小鼠喂食 AGE+ 饮食或 AGE− 饮食。我们通过免疫检测和免疫组织化学检查了血清和大脑皮层中 AGE 加合物的水平，通过生化分析测定了活性氧的水平，检测了与线粒体呼吸链复合物 I 和 IV 以及 ATP 水平相关的酶活性，并通过莫里斯水迷宫和筑巢行为评估了学习和记忆能力。与 AGE− 组相比，AGE+ 饮食喂养的小鼠血清和大脑中 AGE 加合物（MG-H1 和 CEL）的水平显着增加。此外，与 AGE− 组相比，AGE+ 饮食喂养的小鼠明显出现活性氧水平显着升高、线粒体呼吸链复合物 I 和 IV 活性降低、ATP 水平降低以及学习和记忆受损。这些结果表明，膳食AGEs是体内AGE积累的重要来源，导致线粒体功能障碍、能量代谢受损以及随后的认知障碍。因此，减少 AGEs 摄入量以降低 AGEs 积累可能具有预防和治疗 AGEs 诱导的与认知能力下降相关的线粒体功能障碍的治疗潜力。
Advanced glycation end products (AGEs) are an important risk factor for the development of cognitive decline in aging and late-onset neurodegenerative diseases including Alzheimer’s disease. However, whether and how dietary AGEs exacerbate cognitive impairment and brain mitochondrial dysfunction in the aging process remains largely unknown. We investigated the direct effects of dietary AGEs on AGE adducts accumulation, mitochondrial function, and cognitive performance in mice. Mice were fed the AGE+ diet or AGE− diet. We examined levels of AGE adducts in serum and cerebral cortexes by immunodetection and immunohistochemistry, determined levels of reactive oxygen species by biochemical analysis, detected enzyme activity associated with mitochondrial respiratory chain complexes I & IV and ATP levels, and assessed learning and memory ability by Morris Water Maze and nesting behavior. Levels of AGE adducts (MG-H1 and CEL) were robustly increased in the serum and brain of AGE+ diet fed mice compared to the AGE− group. Furthermore, greatly elevated levels of reactive oxygen species, decreased activities of mitochondrial respiratory chain complexes I & IV, reduced ATP levels, and impaired learning and memory were evident in AGE+ diet fed mice compared to the AGE− group. These results indicate that dietary AGEs are important sources of AGE accumulation in vivo, resulting in mitochondrial dysfunction, impairment of energy metabolism, and subsequent cognitive impairment. Thus, reducing AGEs intake to lower accumulation of AGEs could hold therapeutic potential for the prevention and treatment of AGEs-induced mitochondrial dysfunction linked to cognitive decline.