Mapping of regional brain activation in response to fatigue-load and recovery in rats with c-Fos immunohistochemistry

Fatigue is known to be accompanied by a feeling of extreme physical or mental tiredness, resulting from severe stress and hard physical or mental work. To investigate the functional localization of neural activity related to fatigue and recovery, we examined brain c-Fos expression patterns in a rat in a state of fatigue in which rats kept in a cage filled with water to a height of 2.2 cm for 1–5 days. A significant increase in the number of c-Fos-immunopositive cells was observed in the retrosplenial granular b cortex during the fatigue-loading and in the dentate gyrus of the ventral hippocampus after a 24-h recovery. In addition, variable increases in the number of c-Fos-immunopositive cells were observed in the cingulate cortex area 2, ventral part of the lateral septum nucleus, median preoptic nucleus, anterior part of the paraventricular thalamic nucleus, medial parvicellular part of the paraventricular hypothalamic nucleus, and lateral and ventrolateral periaqueductal gray during the fatigue-load period. These results indicate that such regional brain activity would be involved in fatigue or in subsequent recovery and might provide a foothold for further research into the nature of fatigue.