Therapeutic Effects of High-Intensity Interval Training Exercise Alone and Its Combination with Ecdysterone Against Amyloid Beta-Induced Rat Model of Alzheimer's Disease: A Behavioral, Biochemical, and Histological Study.

Hippocampal oxidative stress has a vital role in the pathophysiology of Alzheimer's disease (AD)-associated behavioral deficits. Ecdysterone (Ecdy), a natural product and primary steroid hormone, exhibits anti-oxidative and neuroprotective effects. High-intensity interval training (HIIT) has emerged as an effective method for improving physiological brain functions. The present study was designed to investigate the comparative effects of separate and combined HIIT and Ecdy treatment on behavioral functions, hippocampal oxidative status, histological changes in an amyloid-beta (Aβ)-induced rat model of AD. Adult male rats were treated simultaneously with HIIT exercise and Ecdy (10 mg/kg/day; P.O.), starting ten days after Aβ-injection, and they continued for eight consecutive weeks. At the end of the treatment course, the behavioral functions of the rats were assessed by commonly-used behavioral paradigms. Subsequently, brain samples were collected for histological analysis and hippocampus samples were collected for biochemical analysis. Results illustrated that Aβ injection impaired learning and memory performances in both novel object recognition and Barnes maze tests, reduced exploratory/locomotor activities in open field test, enhanced anxiety-like behavior in elevated plus-maze (P < 0.05). These behavioral deficits accompanied hippocampal oxidative stress (decreased total antioxidant capacity content and glutathione peroxidase enzyme activity, increased total oxidant status and malondialdehyde level) and neuronal loss in the cerebral cortex and hippocampus in H&E staining (P < 0.05). HIIT and Ecdy improved anxiety-like behavior, attenuated total oxidant status and malondialdehyde, and prevented the neuronal loss (P < 0.05). However, their combination resulted in a more complete and powerful improvement in all the above-mentioned Aβ-related deficits (P < 0.05). Overall, these data provide evidence that a combination of HIIT and Ecdy treatment improves Aβ-induced behavioral deficits, possibly through ameliorating hippocampal oxidative status and preventing neuronal loss.