Ameliorative effects of astaxanthin on brain tissues of alzheimer’s disease-like model: cross talk between neuronal-specific microRNA-124 and related pathways

• Published in: Molecular and cellular biochemistry 2021-05, Vol.476 (5), p.2233-2249
• Main Authors: Hafez, Hala A., Kamel, Maher A., Osman, Mohamed Y., Osman, Hassan MY, Elblehi, Samar S., Mahmoud, Shimaa A.
• Format: Article
• Language: English
• Subjects: Acetylcholine; Acetylcholinesterase; Advertising executives; Aluminum; Aluminum chloride; Alzheimer's disease; Amine oxidase (flavin-containing); Amyloid beta-protein; Amyloid precursor protein; Analysis; Antioxidants; Astaxanthin; Biochemistry; Biomedical and Life Sciences; Brain; Cardiology; Cerebral cortex; Chemical compounds; Cognitive ability; Crosstalk; Dementia disorders; Dimethyl sulfoxide; Dosage; Enzymes; Health aspects; Inflammation; Life Sciences; Malondialdehyde; Medical Biochemistry; MicroRNA; MicroRNAs; miRNA; Model testing; Monoamine oxidase; Neurodegenerative diseases; Neurons; Neuroprotection; Oncology; Pharmacology; Ribonucleic acid; RNA; Serotonin; Target marketing; Tissue analysis; β-Site APP-cleaving enzymes
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-021-04079-4

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 β 1-42 and malondialdehyde. Also, significantly inhibit acetylcholinesterase and monoamine oxidase activities and the expression of β-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. Graphic abstract