Aged mice show a reduction in 5-HT neurons and decreased cellular activation in the dentate gyrus when exposed to acute running.

Serotonin (5-HT) is an important neurotransmitter for cognition and neurogenesis in the dentate gyrus (DG), which occurs via movement stimulation such as physical activity. Brain 5-HT function changes secondary to aging require further investigation. We evaluated whether aged animals would present changes in the number of 5-HT neurons in regions such as the dorsal (DRN) and median (MRN) raphe nuclei and possible changes in the rate of cellular activation in the DG in response to acute running, as a reduction in 5-HT neurons could contribute to a decline in neuronal activation in the DG in response to physical activity in aged mice. This study was conducted on adult (3 months old) and aged (19 months old) male and female mice. Immunohistochemistry, microscopic analysis, and treadmill-running tests were also performed. The data revealed that in aged mice, a reduction in the number of 5-HT neurons in the DRN and MRN of male and female mice was observed. The reduction in the DRN was greater in females. Furthermore, aged animals demonstrate a lower rate of c-Fos labeling in the DG when stimulated by physical exercise. These data indicate that aging may be associated with a reduction in the number of 5-HT neurons in the DRN and MRN, which may lead to a decline in 5-HT availability in the target regions, including the DG. The reduced c-Fos expression in the DG after running in aged mice indicates a decreased response to physical activity, which is potentially linked to serotonergic deficits.