The effects of chronic administration of pioglitazone on learning and memory in streptoztocin rat model of Alzheimer’s disease

Background: Alzheimer’s disease (AD) is a chronic neurodegenerative disease characterized by abnormal protein accumulation, synaptic dysfunction, and cognitive impairment. Peroxisome proliferator-activated gamma receptors (PPARγ) play a crucial role in regulating insulin sensitivity and may serve as potential therapeutic targets for AD. Pioglitazone (Piog) as a PPARγ   agonist reduce β-amyloid and tau proteins, and inhibit neuroinflammation. Objective:  we aimed to investigate the effects of chronic administration of pioglitazone on learning and memory in streptozocin (STZ) rat model of Alzheimer’s disease Methods: Animals were divided into 2 groups:  Control and Alzheimer’s rats group include (STZ, STZ + DMSO and STZ + Piog groups) which were the Alzheimer’s rats and received DMSO and Piog (10mg/kg per d) for 21 days. For induction of AD, STZ (3 mg/kg, 10 μl/injection site) were administered into lateral ventricles. All rates were trained in the Morris water maze. Findings: our results show that Piog impaired spatial learning and memory in normal rats. Our results also show that  i.c.v. injection of STZ significantly increased escape latency and Swimming distance to find the hidden platform in comparison with the control group (P<0.05). The amnesic effect of STZ was prevented with Piog So that  The latency time and Swimming distance to find the platform in the STZ+ Piog group rats were significantly lower than STZ + DMSO groups (P<0.05). Conversely, the percentage of time spent and distance swimming in the target quadrant in the probe test in the STZ+ Piog group rats were significantly higher than those in the STZ + DMSO group.  Conclusion: Piog, impaired spatial learning and memory in normal rats but Piog, improved, learning and memory in the STZ rat model of AD. The results suggest that treatment with Piog is useful for treatment of cognitive impairment in AD.