Effect of Diabetes Mellitus on Rat Cognitive Functions and Related Hippocampal Synaptic Plasticity Markers

Cognitive dysfunction is a common complication of diabetes mellitus however, less addressed and recognized. This study aimed to investigate the effect of type 1 and 2 diabetes on cognitive functions and related markers of hippocampal synaptic plasticity and the possible impact of blocking NMDA receptors by memantine. Seven rat groups were included in this study: Non-diabetic, non-diabeticmemantine treated, type-1 diabetic: Untreated, treated with insulin alone and treated with insulin and memantine and type 2 diabetic groups: Untreated and memantine treated. Cognitive functions were assessed by Morris Water Maze and passive avoidance test and immunohistochemistry was used for detection of hippocampus pre and post-synaptic markers: Synaptophysin and postsynaptic density protein-95 (PSD-95) respectively. Both type 1 and 2 untreated diabetic groups showed significantly impaired cognitive performance with concomitant decrease in synaptophysin and PSD-95 compared to the non-diabetic group. Treating type 1 diabetic group with insulin alone significantly improved cognitive performance and PSD-95 compared to untreated type 1 group. Blocking NMDA receptors by memantine (30mg/kg/day) for 3 weeks significantly increased cognitive performance and synaptophysin in type 1 insulin-memantine group compared to type 1-insulin group and significantly increased synaptophysin and PSD-95 in type 2-memantine group compared to the untreated type 2 diabetic group. In conclusion, cognitive functions are impaired in both types of diabetes mellitus and can be improved by blockage of NMDA receptors which may spark future therapeutic role of these receptors in diabetesassociated cognitive dysfunction.