Treadmill exercise enhances the promoting effects of preconditioned stem cells on memory and neurogenesis in Aβ-induced neurotoxicity in the rats

Improving the environment of the injured area and the preconditioning of mesenchymal stem cells (MSCs) are promising approaches to optimize the therapeutic properties of transplanted MSCs. Herein we investigated the synergistic effects of treadmill exercise and dimethyloxalylglycine (DMOG)-preconditioned stem cells in an Alzheimer's disease (AD) animal model. The MSCs were treated with DMOG for 24 h and transplanted in the AD model intravenously. In addition to cell transplantation, the rats went on treadmill exercise for one month. Memory function, BDNF expression, neurogenesis, apoptosis, and antioxidant capacity were assessed using shuttle box and Morris water maze tasks, ELISA, immunohistochemistry, western blot, and biochemical methods. Transplantation of DMOG-treated cells caused a memory improvement compared to the AD group via an increase in neurogenesis and expression of nestin, Sox-2, and NeuroD. Moreover, the injection of preconditioned cells was more effective in increasing the total antioxidant capacity and the BDNF level and decreasing the MDA and caspase-3 than the non-treated cells. Treadmill exercise improved spatial memory and learning through an increase in BDNF and neurogenesis. Finally, treadmill exercise and transplantation of the treated cells together had the most neuroprotective effects. It seems that the transplantation of DMOG-treated cells besides exercise may have protective effects in the AD model via an increase in BDNF, antioxidants, and neurogenesis and a decrease in apoptosis. [Display omitted]