Brain endothelial HIF-1<i>α</i> exacerbates diabetes-associated cognitive impairment by accelerating glycolysis-driven lactate production.

ABSTRACT: Type 2 diabetes (T2D) is an independent risk factor for cognitive impairment. The dysregulation of hypoxia inducible factor (HIF) signaling in T2D patients results in impaired adaptive responses to hypoxia, thereby accelerating the progression of complications. However, limited knowledge is available regarding its precise function in diabetes-associated cognitive impairment (DACI). Here, elevated HIF-1α levels were observed in brain endothelial cells (ECs) of db/db mice. Functionally, brain ECs-specific knockdown of H if1 a significantly ameliorated T2D-induced memory loss and neuronal damage. Glycolysis in brain ECs was inhibited in this process, as indicated by RNA-seq, leading to decreased hippocampal lactate production through reduced LDHA expr

SUBMITTER: Chen J 

PROVIDER: S-EPMC12648004 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature