糖尿病认知功能障碍小鼠海马中 m6A 酶的表达及 YTHDF1 的可能改善作用。
The expression of m6A enzymes in the hippocampus of diabetic cognitive impairment mice and the possible improvement of YTHDF1.
机构信息
The First Affiliated Hospital, Department of Endocrinology and Metabolism, Hengyang Medical School, University of South China, 421001 Hengyang, Hunan, China.
The First Affiliated Hospital, Department of Endocrinology and Metabolism, Hengyang Medical School, University of South China, 421001 Hengyang, Hunan, China; The First Affiliated Hospital, Institute of Clinical Medicine Center, Hengyang Medical School, University of South China, 421001 Hengyang, Hunan, China.
出版信息
Brain Res. 2022 Feb 15;1777:147766. doi: 10.1016/j.brainres.2021.147766. Epub 2021 Dec 23.
Cognitive impairment is a severe diabetes-related complication and seriously challenges the demand for future health resources. However, the potential therapeutic targets and mechanisms are not fully understood. Herein, we investigated the expression of the m6A enzyme in the hippocampus of mice with diabetes-induced cognitive impairment and possible improvement with overexpression of YTHDF1. A type 1 diabetes (T1D) mouse model was established by streptozotocin (STZ) intraperitoneal injection. Diabetic mice showed significant cognitive dysfunction, which was detected by novel object recognition tests and novel place recognition tests. Western blot analysis showed that compared with the control group, the protein levels of YTHDC2 and ALKBH5 were significantly upregulated in the hippocampus in the STZ group, while the expression of YTHDF1, YTHDF3 and WTAP was significantly downregulated. Furthermore, overexpression of YTHDF1 by AAV-YTHDF1 injection in the hippocampus significantly improved STZ-induced diabetic cognitive dysfunction. These results indicate that the m6A enzyme may play a key role in the cognitive dysfunction induced by diabetes, and YTHDF1 may be a promising therapeutic target.
认知障碍是一种严重的糖尿病相关并发症，严重挑战了未来卫生资源的需求。然而，其潜在的治疗靶点和机制尚不完全清楚。在此，我们研究了糖尿病诱导认知障碍小鼠海马中 m6A 酶的表达情况，以及过表达 YTHDF1 可能的改善作用。通过腹腔注射链脲佐菌素（STZ）建立 1 型糖尿病（T1D）小鼠模型。新物体识别试验和新场所识别试验检测到糖尿病小鼠表现出明显的认知功能障碍。Western blot 分析表明，与对照组相比，STZ 组小鼠海马中 YTHDC2 和 ALKBH5 的蛋白水平显著上调，而 YTHDF1、YTHDF3 和 WTAP 的表达显著下调。此外，AAV-YTHDF1 注射到海马中过表达 YTHDF1 可显著改善 STZ 诱导的糖尿病认知功能障碍。这些结果表明，m6A 酶可能在糖尿病诱导的认知功能障碍中发挥关键作用，YTHDF1 可能是一种有前途的治疗靶点。
Zotero 插件