High glucose- or AGE-induced oxidative stress inhibits hippocampal neuronal mitophagy through the Keap1-Nrf2-PHB2 pathway in diabetic encephalopathy.

ABSTRACT: Diabetic encephalopathy (DE) is a severe complication of diabetes, but its pathogenesis remains unclear. This study aimed to investigate the roles and underlying mechanisms of high glucose (HG)- and advanced glycosylation end product (AGE)-induced oxidative stress (OS) in the cognitive decline in DE. The DE mouse model was established using a high-fat diet and streptozotocin, and its cognitive functions were evaluated using the Morris Water Maze, novel object recognition, and Y-maze test. The results revealed increased reactive oxygen species (ROS) generation, mitophagy inhibition, and decreased prohibitin 2 (PHB2) expression in the hippocampal neurons of DE mice and HG- or AGE-treated HT-22 cells. However, overexpression of PHB2 reduced ROS generation, reversed mitophagy inhibition, and i

SUBMITTER: Xu S 

PROVIDER: S-EPMC11473637 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature