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

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Abstract

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 (AlCl3.6H2O) 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 β1-42 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.

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This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Biochemistry Department, Medical Research Institute, Alexandria University, 165 El-Horreya Avenue, EL-Hadara, POB: 21561, Alexandria, Egypt

    Hala A. Hafez, Maher A. Kamel, Mohamed Y. Osman, Hassan MY. Osman & Shimaa A. Mahmoud

  2. Department of Pathology, Faculty of Veterinary Medicine, Alexandria University, Edfina, 22758, Egypt

    Samar S. Elblehi

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  1. Hala A. Hafez
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  2. Maher A. Kamel
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Contributions

HA. Hafez was involved in experiments, interpretation of the data, and writing the article. MA.K and MY.O were involved in the design of the experiments, interpretation of the data, and writing the article, HMY. O was involved in experiments, SS.E was involved in the histopathological examination, interpretation of the data, and writing the article, and SA. M was involved in the design of the experiments, data analysis, and writing and revising the article.

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Correspondence to Hala A. Hafez.

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Approval was obtained from the Institutional Animal Care And Use Committee (IACUC)-Alexandria University, Egypt (Approval Number: AU0122081232). The study also follows ARRIVE guidelines and complies with the National Research Council’s guide for the care and use of laboratory animals.

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Hafez, H.A., Kamel, M.A., Osman, M.Y. et al. Ameliorative effects of astaxanthin on brain tissues of alzheimer’s disease-like model: cross talk between neuronal-specific microRNA-124 and related pathways. Mol Cell Biochem 476, 2233–2249 (2021). https://doi.org/10.1007/s11010-021-04079-4

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