The effect of streptozotocin induced diabetes on inflammasome mediated neuroinflammation and hippocampal learning

Diabets mellitus is associated with impaired learning and memory. Neuroinflammation is a pathophysiological hallmark of diabetes which include production of cytokines. It was suggested that nitrative injury has been implicated in the pathophysiologic mechanism of diabetes. Nod-like receptor family pyrin domain inflammasomes are important in the development of inflammatory response through production of IL-1β and IL-18. In our study, we investigated the effect of oxidative stress and the role of inflammation in the formation of learning disorders caused by diabetes. For this purpose, we examined the levels of nitrotyrosine, NLRP3 and IL-1β in the hippocampus of diabetic rats. In our study, 24 adult male Wistar-Albino rats were used. The experimental animals were divided into two groups: 1) normoglycemic control (n: 12), 2) diabetic control (n: 12). The rats in diabetic model were induced by single dose streptozotocin (60 mg/kg) intraperitoneal injection. Body weight and blood glucose were measured until euthanasia. Morris water maze was used to evaluate the cognitive function in rats. Nitrotyrosine, NLRP3 inflammation and IL-1β levels were measured by ELISA method in hippocampus tissue. Statistically analyses were performed by Mann Whitney U test. At the end of 4 weeks, the body weight of diabetic rats decreased and blood glucose levels were significantly increased. NLRP3 and nitrotyrosine levels were found to be increased in hippocampus of diabetic rats. There was no statsitical significance in the hippocampal IL-1β level with diabetes. In the Morris water maze, diabetic rats spent more time to find the submerged platform when compared with control rats, implying a significant impairment of learning, this impairment was found to be statistically signifcant at day 5. Our results indicate that streptozotocin induced diabetes causes learning impairment in rats probably by generating nitrosative stress and increasing NLRP3 level in the hippocampus.