Voluntary Wheel Running Contributes To Functional Recovery And Neural Plasticity In Mice With The Genetic Absence Of The Corticospinal Tract

Prenatal damage of the corticospinal tract（CST）is the main cause of movement deficits in patients with cerebral palsy,in which there are few effective treatments in clinic.Our previous studies showed that mutant mice with the genetic absence of the CST(Emx1–Cre;Celsr3^f/-genotype)behaved somewhat spontaneous plasticity of the motor-networks,which partially overtook the CST function.Here,we studied the contributions of voluntary wheel running in neural plasticity and functional improvement in Emx1–Cre;Celsr3^f/-mice and the potential mechanisms.Adult mutants were randomly divided into the running and the non-running groups:continuously taking wheel running for 12 weeks and with no interventions respectively.In the running group,there were significant increase of gripping strength,reduction of footslip errors and improvement of food-pellet taking after 8-week exercise assessed by behavioral analysis,compared to the non-running group.These improvements were further supported by the morphology studies:a 16%increase in the number of neuromuscular junctions and the increment of weight and volume,and the elevated amplitude of electromyography recording in bioceps of the running group.In the running group,terminal ramifications of monoaminergic and rubrospinal descending axons were significantly increased in spinal segments after 12-week exercise,and the number of proliferating cells indicated by EDU labeling was 4.8 times of that in the non-running group,90%of which were positive for olig2.Global gene expression levels were analyzed to found differential expressed genes（DEGs）.GO functional enrichment and pathway analysis showed that DEGs were related to gap junction（q=0.023）and phagosome.Protein levels of PSD95 and SY38 were analyzed by western blotting,which were found increased after running.In this process,inflammation-related factors were not change in spinal cord.In conclusions,the voluntary exercise contributes to terminal ramifications of monoaminergic and rubrospinal descending axons and oligodendrocyte genesis,the elevated expression of synapse and myelination related protein,which may be related to neural plasticity and functional improvement in mice lacking corticospinal inputs.This provides us the basic knowledge of exercise rehabilitation for the cerebral palsy in clinic.