Mahdieh Sadat Hosseini, Mona Saheli, Mohammad Amin RajiZadeh, Seyyed Noureddin Nematollahi-Mahani, Sara Joushi, Abbasali Gaeini, Kayvan Khoramipour, Vahid Sheibani
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline. Although high-intensity interval training (HIIT) and mesenchymal stem cells (MSCs) have demonstrated neuroprotective effects, their comparative efficacy has not been compared. Male Wistar rats were assigned to five groups: Control, Vehicle, AD, AD + HIIT, and AD + MSCs. AD was induced by intracerebroventricular (ICV) injection of amyloid-beta (Aβ1-42). HIIT was performed for six weeks, and MSCs were injected via ICV. Learning and memory were evaluated using the Morris water maze (MWM), and CA1 cell number was assessed by Nissl staining. Levels of tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), malondialdehyde (MDA), total antioxidant capacity (TAC), superoxide dismutase (SOD), and brain-derived neurotrophic factor (BDNF) were measured in the hippocampus. Aβ1-42 impaired learning and memory and decreased CA1 cell number, whereas MSCs increased CA1 cell number compared with the AD group (P < 0.05). Aβ1-42 injection increased TNF-α and MDA (both P < 0.001) and decreased IL-10, BDNF (P < 0.01), SOD, and TAC (both P < 0.001). Both HIIT and MSCs improved cognitive performance and modulated biochemical markers compared with AD (P < 0.05). Compared with HIIT, MSCs produced greater reductions in TNF-α (P < 0.01) and greater increases in SOD and TAC (both P < 0.05). Despite these biochemical differences, no significant cognitive function difference was observed between HIIT and MSCs (P > 0.05). These findings suggest that, within the conditions of this study, both HIIT and MSCs administration were associated with improved cognitive performance, with no significant difference in effectiveness between the two treatments. HIIT may therefore be a promising non-pharmacological intervention, but further research is needed to confirm its benefits.