Effects of the combination of high-intensity interval training and Ecdysterone on learning and memory abilities, antioxidant enzyme activities, and neuronal population in an Amyloid-beta-induced rat model of Alzheimer?s disease

Aims: Oxidative stress and neuronal death are the primary reasons for the progression of amyloid-beta (A beta) deposition and cognitive deficits in Alzheimer's disease (AD). Ecdysterone (ecdy), a common derivative of ecdysteroids, possesses free radical scavenging and cognitive-improving effects. High-intensity interval training (HIIT) can be a therapeutic strategy for improving cognitive decline and oxidative stress. The present study was aimed to evaluate the effect of HIIT exercise and ecdy consumption synergistically on the changes in learning and memory functions, activities of hippocampal antioxidant enzymes, and neuronal population after AD induced by A beta in male rats.Materials and methods: Following ten days of A beta injection, HIIT exercise and ecdy treatment (10 mg/kg/day; P.O.) were initiated and continued for eight consecutive weeks in rats. At the end of the treatment period, the rat's learning and memory functions were assessed using Morris water maze and passive avoidance tests. The activity of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GRx), and changes in neuronal population were evaluated in rats' brains.Results: The results indicated that A beta injection disrupted spatial/passive avoidance learning and memory in both tests, accompanied by a decrease in the SOD and CAT (as endogenous antioxidants) in rats' hippocampus. Additionally, A beta injection resulted in neuronal loss in the cerebral cortex and hippocampus. Although the consumption of ecdy separately improved spatial/passive avoidance learning and memory impairments, recovered hippocampal activity of SOD, CAT, GRx, and prevented the hippocampal neuronal loss, its combi-nation along with HIIT resulted in a more powerful and effective amelioration in all the above-mentioned A beta-neuropathological changes.Conclusion: Our results confirm that a combination of HIIT and ecdy treatment could be a promising potential therapeutic option against AD-associated cognitive decline, owing to their free radical scavenging and neuro-protective properties.