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Abstract
Background: Alzheimer's disease represents a progressive neurodegenerative disorder characterized by substantial cognitive deterioration and frequently accompanied by behavioral manifestations, particularly anxiety. While contemporary therapeutic interventions predominantly target cognitive deficits, they inadequately address anxiety related symptoms. This investigation examined the neurotherapeutic potential of Ritonavir (a protease inhibitor) within an aluminum chloride (AlCl3) - induced model of Alzheimer's disease, focusing specifically on its anxiolytic properties and capacity to modulate APOE4 gene expression.
Objective: The primary objective was to evaluate the anxiolytic efficacy and molecular regulatory effects of Ritonavir across multiple dosing regimens (100, 200, and 400mg/kg) in disease-model mice, comparing its therapeutic profile against Donepezil and control groups. Methods: Fifty-six mice underwent randomized allocation into seven experimental cohorts. Anxiety-related behaviors were assessed using the Elevated Plus Maze paradigm, while exploratory tendencies were quantified via the Hole Board Test. Hippocampal APOE4 gene expression patterns were determined through quantitative real-time polymerase chain reaction (RT-qPCR) methodology. Results: Behavioral assessments demonstrated that the highest Ritonavir concentration
(400mg/kg) produced significant anxiolytic effects in the Elevated Plus Maze, evidenced by increased open-arm exploration duration (p < 0.05) relative to AlCl₃-induced disease controls. This dosage exhibited comparable efficacy to Donepezil. Furthermore, the 400mg/kg cohort demonstrated enhanced exploratory behavior in the Hole Board assessment. Molecular analysis revealed that Ritonavir 400mg/kg effectively normalized APOE4 transcriptional levels toward baseline parameters, demonstrating statistical superiority over lower concentrations and the reference medication (p < 0.05). Conclusion: Ritonavir at 400mg/kg exhibits robust anxiolytic properties coupled with favorable APOE4 gene expression modulation, suggesting potential utility as a dual-mechanism therapeutic agent capable of addressing both behavioral symptomatology and molecular pathogenesis in Alzheimer's disease.
Objective: The primary objective was to evaluate the anxiolytic efficacy and molecular regulatory effects of Ritonavir across multiple dosing regimens (100, 200, and 400mg/kg) in disease-model mice, comparing its therapeutic profile against Donepezil and control groups. Methods: Fifty-six mice underwent randomized allocation into seven experimental cohorts. Anxiety-related behaviors were assessed using the Elevated Plus Maze paradigm, while exploratory tendencies were quantified via the Hole Board Test. Hippocampal APOE4 gene expression patterns were determined through quantitative real-time polymerase chain reaction (RT-qPCR) methodology. Results: Behavioral assessments demonstrated that the highest Ritonavir concentration
(400mg/kg) produced significant anxiolytic effects in the Elevated Plus Maze, evidenced by increased open-arm exploration duration (p < 0.05) relative to AlCl₃-induced disease controls. This dosage exhibited comparable efficacy to Donepezil. Furthermore, the 400mg/kg cohort demonstrated enhanced exploratory behavior in the Hole Board assessment. Molecular analysis revealed that Ritonavir 400mg/kg effectively normalized APOE4 transcriptional levels toward baseline parameters, demonstrating statistical superiority over lower concentrations and the reference medication (p < 0.05). Conclusion: Ritonavir at 400mg/kg exhibits robust anxiolytic properties coupled with favorable APOE4 gene expression modulation, suggesting potential utility as a dual-mechanism therapeutic agent capable of addressing both behavioral symptomatology and molecular pathogenesis in Alzheimer's disease.
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