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<0.01). Ang-(1–7) treatment ameliorated damage to the ultrastructure of hippocampal synapses, reduced the expression of hippocampal phospho-tau at Ser396 (P<0.01), Ser404 (P<0.01) and Ser202/Thr205 (P<0.05), and decreased amyloid-β oligomer and both soluble and insoluble β-amyloid peptide 1–42 (Aβ 1–42) and Aβ 1–40 levels (P<0.01). These protective effects were significantly reversed by the co-administration of A779. These findings show that Ang-(1–7) is a promising therapeutic target for diabetes-induced cognitive impairment. The neuroprotective effects of Ang-(1–7) were mainly through Mas receptor (MasR) activation.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call