Evaluation of GLP-1 Receptor Agonist Liraglutide in Zebrafish Model of Alzheimer’s Disease using Behavioral and Biochemical Correlates – A Preclinical Study
摘要
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that often leads to dementia, cognitive impairment and neuroinflammation. Studies have demonstrated the neuroprotective effects of GLP-1 receptor agonists in rodent models by enhancing cognition, reducing oxidative stress and mitigating AD pathology. This study aims to investigate the cognitive-enhancing, anxiolytic and neuroprotective effects of Liraglutide in scopolamine-induced zebrafish model of Alzheimer’s disease.
MethodsThis preventive study design includes treatment of Zebrafish with liraglutide (100 µg/kg or 200 µg/kg), donepezil, or imipramine following scopolamine-induced cognitive impairment. Behavioral assessments included the Novel Tank Test (NTT) to measure anxiety-related responses and the T-maze test to evaluate memory function. Biochemical analyses were conducted to assess neuroprotective effects, including antioxidant enzyme activity, lipid peroxidation and acetylcholinesterase (AChE) levels.
ResultsLiraglutide demonstrated anxiolytic-like effect with the 200 µg/kg dose significantly improving exploratory behavior compared to the lower dose. Donepezil demonstrated superior cognitive benefits, while imipramine induced sedative effects. In the T-maze test, liraglutide at 200 µg/kg significantly reversed scopolamine-induced memory deficits and decreased locomotion. Neuroprotective benefits were confirmed by increased antioxidant enzyme activity and reduced lipid peroxidation.
ConclusionLiraglutide significantly reduced cognitive impairment and exhibited neuroprotective effects in a zebrafish model of Alzheimer’s disease. These findings support preclinical evidence for potential therapeutic relevance in Alzheimer’s treatment and reinforce the utility of zebrafish as a translational model for neurodegenerative research.