Angiotensin IV Improves Spatial Memory in Streptozotocin‑induced Diabetic Rats by Reducing Oxidative Stress and Altering BDNF Levels

In this study, we investigated the protective effects of angiotensin IV (Ang IV) on cognitive function in streptozotocin (STZ)‑induced diabetic rats. Male Wistar albino rats, were randomly divided into four groups; control (C), diabetes (Dia, 60 mg/kg, STZ, i.p.), Ang IV (5 μg/kg, s.c.) and Dia+Ang IV. The passive avoidance and Morris water maze (MWM) tests were used to evaluate learning and memory performance. Behavioral tests were carried out between 21 and 30 days after the initial Ang IV injection. Hippocampi were dissected and retained for biochemical and Western blot analysis. The Dia group exhibited the poorest behavioral results, while the Dia+Ang IV group performed highest on the MWM task. Superoxide dismutase, glutathione peroxidase, and malondialdehyde levels increased significantly in the Dia group compared to Dia+Ang IV. Brain‑derived neurotrophic factor (BDNF) and N‑methyl‑D‑aspartate levels were significantly elevated, while levels of GABAA significantly decreased, in the Dia+Ang IV group compared to the Dia group. These findings suggest that peripheral administration of Ang IV ameliorated spatial memory in diabetic rats by decreasing hippocampal oxidative stress and BDNF levels.