Ecdysterone and High-Intensity Interval Training Mitigate Alzheimer's Pathology in Rats: Impacts on Depression, Synaptic Plasticity, and Neuroinflammation

Abstract

The study focuses on the role of neuroinflammation and impaired synaptic plasticity in the progression of Alzheimer's disease caused by amyloid-beta accumulation. It examines the potential therapeutic effects of Ecdysterone, known for its anti-inflammatory and antioxidant properties, and high-intensity interval training, which may also support brain health. The primary goal is to assess how Ecdy and HIIT, alone or combined, influence depressive-like behavior, synaptic function, inflammation, and Aβ buildup in a rat model of AD. Ten days after Aβ administration, treatments began with Ecdy (10 mg/kg/day, orally) and/or HIIT, continuing for 8 weeks. Rats were tested for depression-like behavior using the forced swim test. Brain synaptic plasticity was measured through long-term potentiation at the perforant path-dentate gyrus synapse by analyzing population spike amplitude and fEPSP slope. Congo red staining was used to identify Aβ plaques in the brain, and neuroinflammatory markers were quantified in both the hippocampus and cerebral cortex. Aβ injection led to depression, impaired synaptic plasticity, increased inflammation, and Aβ buildup in the brain. While Ecdy and HIIT individually offered some protection, their combination was significantly more effective in improving depression, restoring synaptic function, reducing inflammation, and decreasing Aβ accumulation in both the hippocampus and cerebral cortex (0.05 > P). This data provides evidence that HIIT, accompanied by Ecdy, improves Aβ-induced depression-like behavior, which may be partly related to the amelioration of synaptic dysfunction, a decrease in neuroinflammation, and suppression of Aβ plaque formation.

Keywords: Alzheimer’s disease (AD); Amyloid-beta (Aβ); Depression; Ecdysterone (Ecdy); High-intensity interval training (HIIT); Long-term potentiation (LTP); Neuroinflammation.