Exercise-Induced MicroRNA Regulation in the Mice Nervous System is Maintained After Activity Cessation

Background: Physical exercise can improve synaptic function and protect the nervous system against many diseases by altering gene regulation. MicroRNAs (miRs) have emerged as vital regulators of gene expression and protein synthesis not only in the muscular system, but also in the brain. Objective: Here we investigated whether exercise-induced miRs expression in the nervous and muscular systems is activity-dependent or it remains regulated even after exercise cessation. Methods: The expression profile of miR-1, -16, and -206 was monitored by RT-PCR in the dorsal root ganglion, in the spinal cord dorsal and ventral horn, and in the soleus muscle of mice after 5 weeks of swimming training and after swimming exercise followed by 4 weeks of sedentary conditions. Control animals consisted of mice that swan daily for 30s during the 5-weeks training period, returning to the non-swimming activity for additional 4 weeks. Results: After exercise, miR-1 was upregulated in all tissues investigated. However, the upregulation of miR-1 continued significantly high in both aspects of the spinal cord and in the soleus muscle. The expression profiles of miR-16, and -206 were increased only in the nervous system. However, miR-16 upregulation persisted in the DRG and in the spinal cord after exercise interruption, whereas miR-206 continued upregulated only in the spinal cord ventral horn. Conclusion: Exercise training can cause long-lasting changes in the expression of miRs independently of exercise maintenance. Spatial and temporal expression of miRs is to some extent dependent on this activity. The data raised a new conceptual hypothesis on the biogenesis of miRs, indicating that long-lasting and systematic exercise can potentially cause irreversible miR regulation after activity cessation.