Effects of Co-Administered Melatonin and Methylphenidate on Cognitive Impairment and Histopathological Alterations in an Alcl₃-Induced Neurotoxicity Model of Alzheimer’S Disease in Balb/C Mice Publisher Pubmed



Mohammadi F ; Koohi M K ; Adeli S ; Hassan J ; Amini A ; Azadbakht A R ; Zayerzadeh E ; Babaei J F
Source: Scientific Reports Published:2026

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and neuropathological hallmarks such as amyloid plaques and neurofibrillary tangles. Environmental factors, including aluminum chloride (AlCl₃) exposure, have been implicated in neurotoxicity and AD pathogenesis. This study evaluated the combined therapeutic effects of methylphenidate (MPH) and melatonin in a mice model of AlCl₃-induced neurotoxicity. Male BALB/c mice were administered AlCl₃ (300 mg/kg, orally) for 15 days, followed by treatment with melatonin (10 mg/kg), MPH (10 mg/kg), or their combination for 7 days. Behavioral tests, including the Morris water maze, open field, and Y-maze, were used to assess cognitive function. Hippocampal tissues were analyzed for oxidative stress markers (SOD, MDA), inflammatory cytokines (TNF-α, IL-10), apoptosis-related proteins (Bax, Bcl-2), and histological changes. The combination treatment significantly improved memory and learning, enhanced antioxidant capacity, reduced lipid peroxidation, and suppressed neuroinflammation and apoptosis. Histological examinations revealed increased neuronal density and CA1 hippocampal volume. These findings demonstrate that co-treatment with melatonin and MPH mitigates key pathological features of AD, suggesting a promising combinatorial strategy for targeting oxidative stress, neuroinflammation, and apoptosis in Alzheimer’s disease. © The Author(s) 2026.