High-intensity interval training combined with cannabidiol supplementation improves cognitive impairment by regulating the expression of apolipoprotein E, presenilin-1, and glutamate proteins in a rat model of amyloid β-induced Alzheimer's disease.

OBJECTIVES: Alzheimer's disease (AD) is a major public concern and one of the primary types of dementia characterized by memory impairment and cognitive decline. Although the properties of exercise training and cannabidiol (CBD) treatments for improving AD have recently been revealed, the exact mechanisms remain unknown. Therefore, this study highlights the interactive impact of high-intensity interval training (HIIT) and CBD administration on improving cognitive impairment in a rat model of amyloid beta (Aꞵ)-induced AD through modulating the expression of apolipoprotein E (APOE), presenilin-1, and glutamate proteins. MATERIALS AND METHODS: After acclimatization, the animals were randomly assigned into seven subgroups: control (CNT), Sham, Alzheimer (AL), Alzheimer + HIIT (AL + HIIT), Alzheimer + cannabidiol (AL + CBD), Alzheimer + CBD + HIIT (AL + CBD + HIIT), and model (sacrificed ten days after surgery to confirm the induction of AD) groups. To induce AD, rats received an intrahippocampal injection of Aꞵ. The animals in exercise groups performed the HIIT protocol, and the rats in CBD groups were administered 20 mg/kg CBD suspended in sesame oil for six weeks. Following the experimental protocol, serum and hippocampus tissue were collected for histopathological and western blot analysis. RESULTS: Our findings indicated that both HIIT and CBD treatments were efficacious in ameliorating Aꞵ deposition and modulating biomarkers of AD, including APOE, presenilin-1, and glutamate. However, the interactive effect of HIIT and CBD supplementation was more effective. CONCLUSION: Our findings demonstrated the positive therapeutic effect of HIIT and CBD interventions, particularly HIIT combined with CBD, on alleviating AD.