2023 Volume 26 Issue 1 Pages 11-20
Brain injury often causes severe motor dysfunction. Previously, we showed that the corticospinal tract (CST) axons are rewired to form an intraspinal circuit that contributes to motor recovery after brain injury in young adult mice. Although brain injury is often suffered by elderly individuals, little is known about the ability of rewiring and functional recovery in aged rodent model. In this study, we examined CST sprouting and functional recovery in aged mice after brain injury and further investigated whether voluntary running could promote them. We found that axon sprouting was limited and motor function was not recovered in aged mice. Contrastingly, voluntary running significantly increased sprouting and enhanced motor recovery. Moreover, we performed RNA sequencing to examine exercise-induced gene expression of motor area changes in aged mice. Expressions of 91 genes increased in exercised aged mice compared to non-exercised mice, in which a set of circadian rhythm-related genes was involved. Accordingly, a day-night activity rhythm was impaired in the aged mice, whereas it was gradually recovered by exercise, similar to the patterns of younger mice. Our study reveals that voluntary running restores circadian rhythms, CST sprouting, and motor recovery after brain injury in aged mice.