The effect of canagliflozin on hippocampal dendrite morphology in a model of Alzheimer's disease induced by intracerebroventricular injection of streptozotocin

Abstract

Alzheimer's disease (AD) and diabetes mellitus (DM) share common pathophysiological features. However, the effects of antidiabetic drugs on neurodegeneration are not completely known. Canagliflozin, a novel option for DM treatment, is a dual inhibitor of sodium glucose co-transporter type 2 (SGLT2) and acetylcholinesterase. The aim of this study is to examine the morphological features of dendrites and dendritic spines of pyramidal neurons in hippocampus of AD model treated with canagliflozin. The model of AD was obtained by intracerebroventricular injection of streptozotocin. Then, the rats were divided into 3 groups: vehicle, donepezil, and canagliflozin. The injections were i.c.v. administered for 7 days. Behavioral tests were performed to evaluate memory, anxiety, and motor functions. Brain tissues were processed by Golgi impregnation method. Pyramidal neurons in the CA1 region were examined using Neurolucida software. Dendritic branching, total dendrite length, dendritic spine density, and dendritic spine types were analyzed. Compared to the vehicle group, the donepezil group and the canagliflozin group exhibited significantly higher dendritic branches (p = 0.0273, p = 0.0195) and total dendrite length (p = 0.0171, p = 0.0360), respectively. The total dendritic spine density (p < 0.0001) and the mushroom-type dendritic spine density (p = 0.0001) were significantly low in the donepezil group compared to the vehicle group. However, canagliflozin did not induce any significant alterations in the dendritic spine density. Canagliflozin treatment was as effective as donepezil treatment on hippocampal dendrite morphology. This morphological framework, indicating dendritic plasticity and remodeling, serve to better understand the cellular effects of canagliflozin. Therefore, our study may contribute to the development of novel strategies for therapy of AD.