Effects of Chronic Administration of Pioglitazone on Learning and Memory in Rat Model of Streptozotocin-induced Alzheimer’s Disease

Abstract

Background: Alzheimer’s Disease (AD) is a chronic neurodegenerative disease characterized by abnormal protein accumulation, synaptic dysfunction, and cognitive impairment. Peroxisome Proliferator-Activated Receptor-γ (PPARγ) play a crucial role in regulating insulin sensitivity and may serve as potential therapeutic targets for AD. Pioglitazone (PIOG), as a PPARγ agonist, reduces β-amyloid and tau proteins, and inhibits neuroinflammation. Objective: This study aims to evaluate the effects of PIOG chronic administration on learning and memory in rat model of Streptozotocin (STZ)-induced AD Methods: Forty-two male Wistar rats were divided into two groups: A. Normal rats divided into three subgroups of Control, Dimethyl Sulfoxide (DMSO), and PIOG; and B. AD rats divided into four subgroups of Vehicle, STZ, STZ+DMSO and STZ+PIOG. The last two AD subgroups received 0.2 mL DMSO and PIOG (10 mg/kg per day) for 21 days. For induction of AD, STZ (3 mg/kg, 10 μl per injection site) were administered into lateral ventricles. All rates were trained under the Morris water maze task. Findings: PIOG impaired the spatial learning and memory in normal rats. Intracerebroventricular injection of STZ significantly increased escape latency and swimming time to find the hidden platform compared to the control group (P