Activation of central Angiotensin-(1-7)/Mas receptor alleviates synaptic damage in diabetes-associated cognitive impairment via modulating AKT/FOXO1/PACAP axis.

ABSTRACT: Synaptic damage is a pathological hallmark of diabetes-associated cognitive impairment (DACI). Angiotensin-(1-7)/Mas receptor has been implicated in regulating peripheral glucose homeostasis and exerting neuroprotective effects on central nervous system. This study investigated the possible roles of Angiotensin-(1-7)/Mas receptor in DACI, aiming to elucidate the molecular mechanisms underlying synaptic damage. We observed a significant reduction of Angiotensin-(1-7) levels in type 2 diabetic patients with mild cognitive impairment and diabetic cognitive impairment mice. Downregulation of Angiotensin-(1-7)/Mas receptor was associated with the decreased synaptic protein expressions in diabetic cognitive impairment mice, and high glucose-stimulated primary hippocampal neurons. Administration

SUBMITTER: Tian S 

PROVIDER: S-EPMC12035909 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature