Resveratrol prevents cognitive deficits by attenuating oxidative damage and inflammation in rat model of streptozotocin diabetes induced vascular dementia

Abstract

Diabetes is one of the risk factors for the development of vascular dementia (VD), leading to endothelial dysfunction and cognitive impairment. Resveratrol has been shown to have antioxidant, antiinflammatory, and neuroprotective effects. The previous studies have also reported that resveratrol improves cognitive and vascular endothelial functions in several pathological conditions. In the present study we aimed to evaluate the effect of resveratrol on cognitive and vascular endothelial function and to explore the mechanisms of its effects in the streptozotocin-induced diabetic rat model of VD. Male Wistar rats were divided into 3 groups (n = 10 in each group): Control, diabetes (DM), DM + resveratrol (DM + RSV) groups. Rats from the DM + RSV group received resveratrol (20 mg/kg/day, ip) for 4 weeks after induction of diabetes and then cognitive functions of the rats were tested by the Morris water maze and a passive avoidance tests. After behavioral tests, endothelial function of thoracic aorta (the endothelium-dependent and -independent vasorelaxant responses) was investigated. To explore the mechanisms of resveratrol, endothelial eNOS, aortic superoxide dismutase (SOD), NADPH oxidase, heme oxygenase-1 (HO-1) levels, TNF-α and IL-1β expressions; serum SOD and NADPH oxidase levels and, hippocampal BDNF, TNF-α and IL-1β expressions were measured. It was shown that DM resulted in severe learning and memory deficits associated with endothelial dysfunction, increased expression of TNF-α and IL-1β, increased oxidative stress levels and decreased expression of eNOS and BDNF. In contrast, resveratrol treatment improved the cognitive decline. It was also found that chronic treatment with resveratrol ameliorated the impaired vascular reactivity. Reveratrol significantly reversed diabetes-induced changes of protein expression. Our data suggest that resveratrol prevents memory deficits, endothelial dysfunction, increased oxidative stress, inflammation and impairment of neurotrophin expression in a VD rat model. Thus, the vasculoprotective and neuroprotective effects of resveratrol may be beneficial in DM patients.

Keywords: Diabetes mellitus; Resveratrol; cognitive impairment; diabetic rats; learning; memory.