Metformin attenuates neurodegeneration in ICV-STZ-induced Alzheimer's model via antioxidant and anti-inflammatory mechanisms: implications for disease-modifying therapy.

Alzheimer's disease (AD) is the leading cause of dementia, accounting for over 60% of cases in older adults. Growing evidence suggests that metformin, a first-line antidiabetic drug, may have neuroprotective properties. This study evaluated metformin's effects in a streptozotocin (STZ)-induced rat model of sporadic AD. Thirty-two male rats were divided into four groups (n = 8/group): Sham, STZ, Metformin, and Metformin + STZ. The AD model was established via bilateral intracerebroventricular STZ injections (3 mg/kg) on days 61 and 63, with metformin administered in drinking water (2 mg/mL) for 82 days. Metformin treatment significantly enhanced hippocampal catalase activity while reducing malondialdehyde (MDA) and total oxidative status (TOS) levels in both brain and serum. Notably, it selectively decreased hippocampal IL-1β without affecting serum levels, suggesting central-specific anti-inflammatory effects. These findings demonstrate metformin's dual antioxidant and anti-inflammatory actions in an AD model, supporting its potential as a disease-modifying therapy. The dissociation between central and peripheral IL-1β responses highlights the importance of blood-brain barrier considerations in AD treatment strategies.