Calcitonin gene-related peptide is increased in hindlimb motoneurons after exercise

Calcitonin gene-related peptide (CGRP) is a neuroactive peptide present in some spinal cord motoneurons and at their motor endplates in skeletal muscle. Although detectable levels of CGRP change after surgical and pharmacological interruptions of neuromuscular connectivity, a clear understanding of its physiological role in the motor system is lacking. The purpose of this study was to investigate whether downhill running exercise, which elicits muscle damage and repair, also elicits changes in CGRP levels in hindlimb motoneurons. Twenty female Wistar rats were divided into five groups: control (c), 48 hours post-exercise (48 hr), 72 hours (72 hr), two weeks (2 wks) and four weeks (4 wks). Exercise groups ran downhill for one 30 minute period. Histological examination of muscle from ankle extensors (triceps surae, TS) and flexors (anterior crural, AC) indicated the characteristic presence of histiocytes by 48 hr postexercise in TS but not in AC. Paraformaldehyde-fixed, 30 mu m sections of lumbar spinal cord (L2-L4) from the same animals were incubated with polyclonal antisera to CGRP. The number of CGRP-positive TS motor nuclei increased significantly by 48 hr after exercise (p=0.001) vs control and returned to baseline values by 4 wks (p>0.05). In contrast, no significant changes were observed in the AC motoneuron pool at any post-exercise interval (p>0.05). The temporal changes in CGRP levels in TS motoneurons suggest that expression of this neuropeptide may be differentially regulated by exercise-induced changes in neuromuscular function, possibly as related to muscle tissue damage/repair mechanisms and thus to remodeling at the neuromuscular junction.