Endurance training and MitoQ supplementation improve spatial memory, VEGF expression, and neurogenic factors in hippocampal tissue of rats

Abstract

The hippocampus has a key role in memory and learning, which means that this brain structure has high-energy demand. Accordingly, mitochondrial dysfunction in the hippocampus has deleterious effects on brain function. MitoQ is an antioxidant that accumulates selectively in mitochondria at high concentration. In this study, the effect of MitoQ alone and in combination with endurance training (ET) was investigated on spatial memory (distance, time, and number of passes in the target quarter), antioxidant status (superoxide dismutase [SOD] and glutathione peroxidase [GPx]), and neurogenic factor levels (vascular endothelial growth factor [VEGF] and brain-derived neurotrophic factor [BDNF]) in male Wistar rats. Rats were assigned to a control (CTL) group, ET group, ET+MitoQ group, and a MitoQ group. Rats were trained on a treadmill for 8 weeks, 5 days/week, and 50 min/day. MitoQ (250 μM daily) was administered through drinking water for 8 weeks. Spatial memory (Morris water maze test), gene expression (real-time PCR), protein expression (Western blotting), and antioxidants (ELISA method) were determined. Distance and number of passes in the target quarter in the ET, MitoQ, and ET+MitoQ groups were higher than in the CTL group (P=0.001). MitoQ+ET had more impact on the abovementioned indices than MitoQ or ET alone. Simultaneous use of MitoQ and ET significantly increased gene and protein expression of VEGF (P=0.0001) and gene expression of BDNF (P=0.004) and Sestrin 2 (SESN2) (P=0.0001) in hippocampal tissue. The expression of VEGF (P=0.007) and SESN2 (P=0.001) was higher in the MitoQ group compared to the CTL group. Tissue GPx levels were increased following all three interventions (P≤0.013) compared to the CTL group while SOD levels remained unchanged in all groups. The combination of ET and MitoQ has additive effects on spatial memory in rats by modulating parameters that are involved in hippocampal neurogenesis. In addition, MitoQ may have positive effects on the antioxidant defense by improving GPx activity. Considering the positive effects of MitoQ on improving the memory and the antioxidant defense, it seems that it can play a positive role in improving the diseases associated with memory loss in the long term, and ET along with this supplement can increase the possible positive effects.