Pioglitazone ameliorates memory deficits in streptozotocin-induced diabetic mice:involvement of amyioid-β decline via activation of PPAR γ in brain
Aim: To examine the effects of pioglitazone, a PPART agonist, on memory performance and brain amyloidogenesis in streptozotocin (STZ)-induced diabetic mice.Methods: ICR male mice were injected with STZ (150 mg/kg, iv) to induce experimental diabetes.Pioglitazone (9 and 15 mg.kg(-1)-d(-1), po) was administered for 6 weeks.Passive avoidance and Morris water maze (MWM) tests were used to evaluate cognitive function.The blood glucose and serum insulin levels were detected using the glucose oxidase method and an ELISA assay,respectively.β-amyloid (Aβ), β-amyloid precursor protein (APP), βamyloid precursor protein cleaving enzyme 1 (BACEI), NF-kB p65, the receptor for advanced glycation end products (RAGE) and PPARy in the brains were analyzed using Western blotting assays.Results: The STZ-induced diabetic mice characterized by hyperglycemia and hypoinsulinemia performed poorly in both the passive avoidance and MWM tests, accompanied by increased Aβ1-40/Aβ1-42, APE BACEI,NF-r,.B p65 and RAGE levels and decreased PPARγ level in the hippocampus and cortex.Chronic pioglitazone treatment significantly ameliorated the memory deficits and amyloidogenesis of STZinduced diabetic mice, and suppressed expression of APP, BACE1, RAGE and NF-κB p65, and activated PPARγin the hippocampus and cortex.However, pioglitazone did not significantly affect blood glucose and insulin levels.Conclusion: Pioglitazone ameliorates memory deficits in STZ-induced diabetic mice by reducing brain Aβlevel via activation of PPARγ, which is independent of its effects on blood glucose and insulin levels.The results suggest that pioglitazone may be used for treating the cognitive dysfunction in type 1 diabetes mellitus.
pioglitazone peroxisome proliferator-activated receptorγ cognition amyloid-β 13-site amyloid precursor protein cleaving enzyme 1 nuclear factor kappa B receptor for advanced glycation end products β-amyioid precursor protein type 1 diabetes mellitus
Li-ping LIU Mei HU Hao HONG Tian-hua YAN Li-ying JIANG Wei HU Meng HU Qian ZHANG YaN LONG Jiang-Qing WANG Yong-qi LI
Department of Pharmacy, the Second Hospital Affiliated to Anhui Medical University; Hefei 230031, An Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China
国内会议
江苏省药理学会青年工作委员会成立大会暨药理学科青年科技创新学术研讨会
苏州
英文
177-178
2013-05-24（万方平台首次上网日期，不代表论文的发表时间）