Improvement in long term and visuo-spatial memory following chronic pioglitazone in mouse model of Alzheimer's disease

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists (thiazolidinediones) are widely prescribed for the treatment of type-II diabetes mellitus. Recently, PPAR-gamma agonists have shown neuroprotective effects in neurodegenerative disorders. The current study was carried out to investigate the effects of chronic administration of pioglitazone, a PPAR-gamma agonist, on cognitive impairment in a mouse model of Alzheimer's disease induced by scopolamine. Scopolamine was administered in a dose of 1 mg/kg intraperitoneally (i.p.). Cognitive functions were assessed using step-down latency (SDL) on a passive avoidance apparatus and escape latency in Morris water maze test. Pioglitazone was also investigated for its effects on parameters of oxidative stress by measuring malondialdehyde (MDA) and reduced glutathione (GSH) levels in the brain. Scopolamine produced significant reduction in SDL and prolongation of escape latency indicating cognitive impairment in mice. Pioglitazone (20 and 40 mg/kg, i.p.), administered for 21 days, showed significant dose-dependent improvement in scopolamine-induced dysfunctions in long-term and visuo-spatial memory in passive avoidance and Morris water maze tests, respectively. Furthermore, pioglitazone significantly prevented the fall in GSH levels and elevation in brain MDA levels induced by scopolamine. These results demonstrate that pioglitazone offers protection against scopolamine-induced dysfunctions in long-term and visuo-spatial memory, possibly due to its antioxidant action, and therefore, could have a therapeutic potential in Alzheimer's disease. (C) 2012 Elsevier Inc. All rights reserved.