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Combating cognitive decline in a rat model of Alzheimer’s disease: The role of high-intensity interval training and cannabidiol administration in modulating microRNA-124, BACE1, and nestin

Articles in Press

Document Type : Original Article

Authors

1 Department of Exercise Physiology, School of Sport Sciences and Health, University of Tehran, Tehran, Iran

2 School of Sports Science, Ruhr University, Bochum, Germany

Abstract

Background: The global prevalence of Alzheimer’s disease (AD) has emerged as a paramount concern due to the aging population. The current research examines the effects of six-week high-intensity interval training (HIIT), with and without cannabidiol (CBD) supplementation, on cognitive decline, micro ribonucleic acid (miRNA)-124 expression levels, and the protein expression of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) and nestin in the hippocampus of rats with amyloid beta (Aβ)-induced AD.
Methods: 30 male Wistar rats were randomly divided into six groups: control (CNT), sham, Alzheimer (AD), Alzheimer + HIIT (H-AD), Alzheimer + CBD (C-AD), and Alzheimer + HIIT + CBD (CH-AD). Following the hippocampal injection of Aβ1-42, the HIIT protocol and CBD supplementation [20 mg/kg/day, per os (P.O.)] were initiated and conducted over six weeks. After the last intervention, the hippocampus tissues were collected to assess miRNA-124 expression levels and the protein expression of BACE1 and nestin.
Results: HIIT alone and in combination with CBD treatment significantly improved cognitive impairment induced by AD. 
Moreover, both treatments significantly reduced BACE1 protein expression and increased nestin protein expression in AD rats. However, despite decreased miRNA-124 expression levels in the AD group in comparison with the CNT group, HIIT and CBD administration did not alter miRNA-124 expression levels in other groups.
Conclusion: The findings can contribute to a higher understanding of the beneficial effects of HIIT combined with CBD administration in mitigating AD-induced cognitive impairment by reducing BACE1 protein expression and increasing nestin protein expression.

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Current Journal of Neurology

Articles in Press, Accepted Manuscript
Available Online from 04 April 2026
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