Type 2 diabetes mellitus and cognitive deficits in experimental model: a positive correlation

Author(s): Sushma D.S., Natesh Prabhu M., Ullal Sheetal D.*, Sahana D.A., Vinaykumar S., Caron SM D’silva, Ashok Shenoy K.

Abstract

BACKGROUND: Epidemiological studies have shown a positive association between diabetes mellitus and the development of mild to moderate cognitive impairment. Studies in animals also have shown cognitive decline in type 1 diabetic models. Possible mechanisms of cognitive decline in patients of diabetes mellitus are still under research. OBJECTIVE: To evaluate the correlation between hyperglycemia induced by type 2 diabetes mellitus and cognitive deficits, in wistar rats. METHODOLOGY: Thirty Wistar rats were included in the study. Type 2 diabetes mellitus was induced in all the groups except normal control, by administering a single dose of nicotinamide 110mg/kg, followed 15 minutes later by streptozotocin 50mg/kg intraperitonially. Fasting blood glucose (FBG) levels were estimated on the 7th day after induction of diabetes. Rats with FBG >200mg/dl were randomly distributed to four groups – Diabetic control, Glibenclamide, Piracetam, Glibenclamide+Piracetam groups. Baseline values for Time taken to reach reward chamber (TRC), Step through latency (STL) and Transfer latency (TL), using Hebb-William maze, Shuttle box avoidance test and Elevated plus maze respectively, were recorded. The means of five sessions were calculated for each rat. After 30 days of treatment, FBG, TRC, STL and TL were tested for all the groups. Data was analysed using one way ANOVA followed by post hoc Tukey test and paired t test. The correlation between cognitive impairment and blood glucose level was done using Pearson’s correlation. Results: Diabetic control group showed a significant increase in FBG on day 30 {p=0.002, [-197.69 to -76.97]. Glibenclamide group, glibenclamide + piracetam group showed significant reduction in FBG compared to day 1 (p<0.05), and highly significant decrease in FBG compared to the diabetic control group (p<0.0001). Compared to day 1, diabetic control group showed a significant increase in cognitive parameters TRC and STL on day 30 (p=0.001), and it showed a statistically significant increase in TL of both day 1 and day 30 compared to normal control, indicating cognitive impairment. Glibenclamide, piracetam, glibenclamide + piracetam groups showed highly significant decrease in the TRC and STL on day 30 compared to Diabetic Control (p<0.0001), significant decrease in TL (p=0.038, p=0.047, p=0.006 respectively), indicating prevention of cognitive impairment. In Pearson correlation test, moderate linear association was found between FBG and cognition parameters TRC, STL, and TL. Conclusion: A positive correlation exists between hyperglycemia and development of cognitive deficits in type 2 Diabetes mellitus induced animal model.

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