Angiotensin-(1–7) administration attenuates Alzheimer’s disease-like neuropathology in rats with streptozotocin-induced diabetes via Mas receptor activation

Abstract Diabetes mellitus (DM) is associated with cognitive deficits and an increased risk of Alzheimer’s disease (AD). Recently, a newly identified heptapeptide of the renin-angiotensin system (RAS), angiotensin-(1–7) [Ang-(1–7)], was found to protect against brain damage. This study investigated the effects of Ang-(1–7) on diabetes-induced cognitive deficits. Sprague–Dawley rats were randomly divided into four groups. Diabetes was induced via single i.p. streptozotocin (STZ) injections. Ten weeks after diabetes induction, rats in each group received an intracerebral-ventricular (ICV) infusion of either vehicle, Ang-(1–7) alone, or Ang-(1–7) + A779 daily for two weeks. At the end of the study, Morris water maze (MWM) tests were performed to test cognitive functions before the rats were euthanized. Ang-(1–7) treatment significantly reduced escape latencies in diabetic rats in acquisition trials and markedly enhanced platform area crossing frequency and time spent in the target quadrant in probe trials (3.0 ± 0.39 vs. 1.0 ± 0.33, 39.39 ± 1.11% vs. 25.62 ± 3.07%, respectively, P P P P P