Comprehensive Evaluation of Inosine’s Neuroprotective Potential in Streptozotocin-Induced Alzheimer’s-Like Pathology in Wistar Rats: Behavioral, Biochemical and Molecular Insights

Abstract

Alzheimer’s disease (AD) is a debilitating neurodegenerative disorder marked by cognitive decline and neuroinflammation, necessitating innovative treatments. This study assessed the neuroprotective efficacy of inosine (100, 200, and 300 mg/kg) against streptozotocin (STZ)-induced cognitive impairment in male Wistar rats, with Donepezil (5 mg/kg) as a positive control. Thirty rats were randomized into six groups: Vehicle Control, STZ Disease Control, STZ + Donepezil, and STZ + Inosine (three doses). STZ (3 mg/kg, i.c.v.) was administered on Day 1, followed by daily oral treatments for 20 days. Neurobehavioral tests (Morris Water Maze, Y-Maze, Passive Avoidance Test, Elevated Plus Maze) and biochemical assays (TNF-α, IL-1β, BDNF, glutamate, GABA) evaluated cognitive function, anxiety, inflammation, neurotrophic support, and neurotransmitter balance. STZ induced significant cognitive deficits, anxiety-like behavior, elevated proinflammatory cytokines, reduced BDNF, and neurotransmitter imbalances. Donepezil significantly ameliorated all parameters. Inosine demonstrated dose-dependent improvements, with the 300 mg/kg dose nearly matching Donepezil’s efficacy, enhancing memory, reducing anxiety, suppressing inflammation, restoring BDNF, and normalizing neurotransmitter levels (Haskó et al., 2004). ANOVA with Tukey’s post hoc tests confirmed significant group differences (p < 0.05). These results highlight inosine’s potential as a multifaceted therapeutic for AD, warranting further preclinical and clinical investigation.