Hafez_2021_Mol.Cell.Biochem__

Alzheimer's disease (AD) is a chronic, progressive, multifactorial, and the most common neurodegenerative disease which causes dementia and mental deterioration in the elderly. The available treatments for AD are not disease-modifying drugs and only provide symptomatic relief. Astaxanthin (ATX), a second-generation antioxidant, is a dark red carotenoid and exhibits the highest antioxidant capacity, anti-inflammatory, neuroprotective, and antiapoptotic effects. In this study, we investigated the therapeutic effect of different doses of ATX on the cerebral cortex and hippocampus of AD-like rats. The AD-like model was induced in rats using hydrated aluminum chloride (AlCl(3).6H(2)O) solution that was given orally at a dose of 75 mg/kg daily for 6 weeks. Morris water maze (MWM) behavioral test was performed to confirm the cognitive dysfunction then AD-like rats were orally treated with different doses of ATX (5, 10, and 15 mg/kg) dissolved in dimethyl sulfoxide (DMSO) for six weeks. The results indicated that ATX significantly and dose-dependently improved the performance of AD-like rats treated with ATX during MWM and suppress the accumulation of amyloid beta(1-42) and malondialdehyde. Also, significantly inhibit acetylcholinesterase and monoamine oxidase activities and the expression of beta-site amyloid precursor protein cleaving enzyme 1 (BACE 1). ATX also significantly elevated the content of acetylcholine, serotonin, and nuclear factor erythroid-2-related factor 2 (Nrf2) and miRNA-124 expression. The effect of ATX treatment was confirmed by histopathological observations using H&E stain and morphometric tissue analysis. From this study, we concluded that ATX may be a promising therapeutic agent for AD through targeting different pathogenic pathways.