莫里斯水上航行任务
树突棘
海马体
海马结构
红景天苷
链脲佐菌素
内科学
内分泌学
发病机制
突触素
医学
生物
神经科学
作者
Rui Zhang,Lei Jiang,Guofeng Li,JingJing Wu,Pei Tian,Di Zhang,Yushi Qin,Zhongli Shi,ZhaoYu Gao,Nan Zhang,Shuang Wang,Huimin Zhou,Shunjiang Xu
摘要
miR-34c has been found to be implicated in the pathological process of Alzheimer's disease, diabetes, and its complications.To investigate the underlying mechanisms of miR-34c in the pathogenesis of diabetic encephalopathy (DE).Diabetes mellitus rats were developed by incorporating a high-fat diet and streptozotocin injection. Morris water maze test and novel object recognition test were used to assess the cognitive function of rats. Expression of miR-34c were detected by fluorescence in situ hybridization and qRT-PCR. Immunofluorescence and western blot were used to evaluate synaptotagmin 1 (SYT1) and AdipoR2 or other proteins. Golgi staining was performed to investigate dendritic spine density.The increased miR-34c induced by advanced glycation end-products (AGEs) was mediated by ROS-JNK-p53 pathway, but not ROS-Rb-E2F1 pathway, in hippocampus of DE rats or in HT-22 cells. miR-34c negatively regulated the expression of SYT1, but not AdipoR2, in hippocampal neurons. miR-34c inhibitor rescued the AGE-induced decrease in the density of dendritic spines in primary hippocampal neurons. Administration of AM34c by the intranasal delivery increased the hippocampus levels of SYT1 and ameliorated the cognitive function in DE rats. The serum levels of miR-34c were increased in patients with DE comparing with normal controls.These results demonstrated that AGE-induced oxidative stress mediated increase of miR-34c through ROS-JNK-p53 pathway, resulting in synaptic deficits and cognitive decline by targeting SYT1 in DE, and the miR-34c/SYT1 axis could be considered as a novel therapeutic target for DE patients.
科研通智能强力驱动
Strongly Powered by AbleSci AI