title: Pioglitazone ameliorates memory deficits in streptozotocin-induced diabetic mice by reducing brain β-amyloid through PPARγ activation.
abstract: OBJECTIVE
  To examine the effects of pioglitazone, a PPARγ 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 18 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), β-amyloid precursor protein cleaving enzyme 1 (BACE1), NF-κB p65, the receptor for advanced glycation end products (RAGE) and PPARγ 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, APP, BACE1, NF-κB p65 and RAGE levels and decreased PPARγ level in the hippocampus and cortex. Chronic pioglitazone treatment significantly ameliorated the memory deficits and amyloidogenesis of STZ-induced diabetic mice, and suppressed expression of APP, BACE1, RAGE and NF-κB p65, and activated PPARγ in the hippocampus and cortex. However, pioglitazone did not significantly affect blood glucose and insulin levels.
  
  
  CONCLUSIONS
  Pioglitazone ameliorates memory deficits in STZ-induced diabetic mice by reducing brain Aβ level 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.
authors.affiliation: Department of Pharmacy, the Second Hospital Affiliated to Anhui Medical University, Hefei 230031, China.
authors.forename: Li-ping
authors.initials: LP
authors.lastname: Liu
authors.forename: Tian-hua
authors.initials: TH
authors.lastname: Yan
authors.forename: Li-ying
authors.initials: LY
authors.lastname: Jiang
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.forename: Meng
authors.initials: M
authors.lastname: Hu
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Long
authors.forename: Jiang-qing
authors.initials: JQ
authors.lastname: Wang
authors.forename: Yong-qi
authors.initials: YQ
authors.lastname: Li
authors.forename: Mei
authors.initials: M
authors.lastname: Hu
authors.forename: Hao
authors.initials: H
authors.lastname: Hong
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D003071:Cognition / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007328:Insulin / Q000097:blood; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism*; D000077205:Pioglitazone; D011897:Random Allocation; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D001786:Blood Glucose; D007328:Insulin; D016328:NF-kappa B; D047495:PPAR gamma; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D045162:Thiazolidinediones; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse; D000077205:Pioglitazone