2011 Volume 57 Issue 4 Pages 367-371
We have previously hypothesized that mental fatigue is caused by neuronal brain damage through the activation of N-methyl-D-aspartate receptors by quinolinic acid (QUIN). QUIN is a metabolite of tryp-tophan in the kynurenine pathway; this pathway is stimulated by several cytokines, including tumor necrosis factor (TNF)-α. Recently, we proved this mental-fatigue hypothesis by studying stress-loaded and lipopolysaccharide-treated mice. In the present study, we measured blood QUIN levels after exercise in mice to investigate whether QUIN also participates in causing the sensation of fatigue after exercise. In a weight-loaded swimming test, steel wires weighing about 5% of body weight were attached to the tails of mice that were then forced to swim until exhaustion. The serum QUIN levels of swimming mice were significantly higher than those of non-swimming mice. The serum TNF-α levels were also increased in swimming mice compared with non-swimming mice, although this effect was not significant. In a treadmill-running test, mice were forced to run for 150 min on a 10-degree uphill incline. The serum levels of both QUIN and TNF-α were significantly higher in treadmill-running mice than in non-running mice. Wheel-running counts, which reflect mental activity, were also measured in a running wheel-equipped home cage. Wheel-running counts of treadmill-running mice were significantly reduced compared with those of non-running mice. These results suggest that blood QUIN levels are increased after exercise and that this effect occurs through enhanced tryptophan metabolism in the kynurenine pathway due to TNF-α production. It is implied that QUIN participates in the sensation of fatigue after exercise.
