Resveratrol attenuates behavioural impairment associated with learning and memory in rats with diabetes induced by a high‐fat diet and streptozotocin

Abstract

Background and Purpose A high‐fat diet (HFD) is a common risk factor for Type 2 diabetes mellitus (T2DM) and its associated cognitive impairments. In models of diabetes, resveratrol, a modulator of SIRT1, regulates the fasting glucose and antioxidant levels, as well as the lipid profile. Resveratrol may also alleviate the cognitive dysfunctions associated with diabetes. Experimental Approach Albino rats were fed a HFD, (60% kcal fat) after treatment with streptozotocin (45 mg·kg −1 ,i.p., single dose) to induce an experimental model of T2DM. After 14 weeks of the animals in confirmed diabetic condition, they were treated with metformin (200 mg·kg −1 ,i.p.) or resveratrol (50 or 100 mg·kg −1 ,i.p.) for 4 weeks. Levels of oxidative‐nitroso‐stress, SIRT1, TGF‐β1, inflammation and cholinergic activity were determined in plasma, hippocampus and cerebral cortex. A battery of behavioural studies associated with learning memory were performed during and after the experimental protocol. Key Results Treatment with resveratrol attenuated the increased glucose levels (pre‐ and post‐prandial), impaired glucose tolerance, HbA1c, and decreased the body weights of the T2DM rats. Moreover, resveratrol ameliorated the impaired learning and memory associated with increased SIRT1 and decreased TGF‐β1, TNF‐α, oxidative‐nitroso‐stress, and cholinergic activities in the plasma and the brains of the T2DM animals. Conclusion and Implication Our results demonstrated that SIRT1 modulation interacted with TGF‐β1 signalling, and mitigated hyperglycaemia and subsequent learning‐memory impairments in the T2DM animals. Our study also suggested novel therapeutic targets, including TGF‐β1, which may add to our knowledge of resveratrol, when used to treat impaired memory associated with diabetes.

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