Melatonin reverses type 2 diabetes-induced cognitive deficits via attenuation of oxidative/nitrosative stress and NF-κB-mediated neuroinflammation in rat hippocampus

Purpose: To evaluate the protective effect of melatonin on diabetes-induced cognitive dysfunction. Methods: Rats were fed a high-fat diet + streptozotocin (HFD + STZ) for 15 weeks to induce type 2 diabetes (HFD + STZ group). At the end of the 15-week induction of diabetes, cognitive function in the diabetic rats was estimated using a Morris water maze and an object recognition task. Next, the diabetic rats were treated with melatonin (10 mg/ kg, po) for 3 weeks. Thereafter, cognitive function was reevaluated in the melatonin-treated diabetic rats (melatonin group). Results: There was a significant (p < 0.01) decrease in the serum glucose and insulin in melatonintreated diabetes type 2 rats compared with that of diabetes type 2 rats exposed to only HFD + STZ. Treatment with melatonin (10 mg/kg, po) for 3 weeks in diabetic type 2 rats also caused a significant increase (p < 0.01) in the time spent in the target quadrant and preference index in diabetic rats compared with the HFD + STZ group. There were significant decreases in reactive oxygen species (ROS), oxido-nitrosative stress markers, including thiobarbituric acid reactive substances (TBARS), nitrite, and depleted glutathione (GSH) level in the hippocampus of melatonin-treated group, compared with the HFD + STZ-treated group. Moreover, the melatonin-treated group showed significant inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and reduction in the levels of proinflammatory cytokines. Conclusion: The results demonstrate that melatonin prevents cognitive dysfunction in type 2 diabetic rats by attenuating oxido-nitrosative stress and NF-κB-mediated neuroinflammation. This effect suggests that melatonin may be useful for the management of cognitive dysfunction in patients suffering from diabetes. Keywords: Cognitive dysfunction, Melatonin, Neuroinflammation, Nuclear factor kappa-light-chainenhancer of activated B cells (NF-κB), Oxido-nitrosative stress, Type 2 diabetes