Abstract:Objective: To investigate the effects of rosiglitazone on cognitive function in streptozotocin-induced diabetic mice and the underlying mechanisms.Methods: Diabetic mice induced by a single intravenous injection of streptozotocin（150 mg• kg^-1body weigh）were used as animal model of type 1 diabetes. Diabetic mice with hyperglycemia（>11.1 mmol•L^-1）were randomly divided into three groups,including untreated diabetes group, rosiglitazone( 3.2 mg•kg^-1and 1.6 mg•kg^-1)treated groups（10~12 mice/group）. After orally administration of rosiglitazone for 6 w, rosiglitazone-treated diabetic mice, untreated diabetic mice and non-diabetic controls were tested in the Morris water maze and Y maze. The serum insulin，the levels of Aβ₄₀，Aβ₄₂and BACE1 in hippocampus and cortex were determined by ELISA assays，and the blood glucose was measured by the glucose oxidase method.Results: Both water maze and Y maze learning were impaired in diabetic mice. In Morris water maze, rosiglitazone（3.2 mg• kg^-1）significantly decreased the escape latency（P<0.05）and increased the time spent in the platform quadran（P<0.05）compared with the vehicle diabetic group. Rosiglitazone（3.2 mg• kg^-1）also significantly increased the number of correct（P<0.05）in Y maze test. Rosiglitazone treatment did not decrease the blood glucose and serum insulin of diabetic mice. Rosiglitazone（3.2 mg• kg^-1）significantly decreased the Aβ₄₀（P<0.05,P<0.05）and Aβ₄₂（P<0.05,P<0.05）levels in both hippocampus and cerebral cortex of diabetic mice, without reducing the increased BACE1 level.Conclusion: Rosiglitazone at the dosage of 3.2 mg• kg^-1improves cognitive impairments in streptozotocin-induced diabetic mice via the alleviation of the Aβ burden in the brain.

Key words:diabetes mellitus,cognitive impairment,rosiglitazone,&,beta,-amyloid protein（A&,beta,）