A New Vanadium Complex Improves the Spatial Learning and Memory by Activation of Caveolin–MAPK–CREB Pathway in Diabetic Mice

Abstract

Diabetic encephalopathy, characterized by impaired spatial cognitive functions and the decline of learning and memory ability, involves direct neuronal damage caused by intracellular glucose. Vanadium, a required trace element of human body, is reported that it can reduce the blood glucose values of glycemia animals and has an effect on the treatment of diabetes complications. To investigate the role of vanadium in the pathogenesis of diabetic cognitive function impediment, Kunming mice were divided into control group, diabetes group and vanadium-treatment group. Diabetic mice were induced by intraperitoneal injection of 200 mg/kg of alloxan and in vanadium-treatment group diabetic mice were treated by intragastric infusion for three weeks with 5 mg/kg of VO(HB(3,5-Me 2 pz) 3 )(3,5-Me 2 pzH)(SCN)(SCNH) 2 , a new vanadium complex with 3,5-dimethyl-pyrazolyl ligand and relative lower toxicity. The three groups were trained by Morris water maze and then the expression of proteins related to learning and memory in the hippocampus of mice were examined by Western blot. The results showed that (1) the latency to find platform was longer ( p>0.05) and the percent time in target quadrant was lower (p<0.05) in diabetes group compared with that in control group. The learning and memory score of vanadium-treatment group was obviously higher than that of diabetes group (p<0.05) and equivalent with the control group; (2) the phosphorylation level of p42/p44MAPK protein was remarkably decreased in diabetes group and then increased after vanadium treatment. Furthermore, Caveolin-1 expression was remarkably reduced and CREB2 expression was higher in diabetes group while after vanadium treatment caveolin-1 expression was significantly increased. These results suggest that vanadium can improve the learning and memory ability of diabetic mice and its mechanism may be involved in the activation of Caveolin–MAPK–CREB pathway in the neuron.