Slow- and fast-twitch rat hind limb skeletal muscle phenotypes 8 months after spinal cord transection and olfactory ensheathing glia transplantation

Abstract

Paralyzed skeletal muscle of rats with spinal cord injury (SCI) undergoes atrophy and a switch in gene expression pattern which leads to faster, more fatigable phenotypes. Olfactory ensheathing glia (OEG) transplants have been reported to promote axonal regeneration and to restore sensory-motor function in animals with SCI. We hypothesized that OEG-transplants could attenuate skeletal muscle phenotypic deterioration and that this effect could underlie the functional recovery observed in behavioural tests. A variety of morphologic, metabolic and molecular markers were assessed in soleus (SOL) and extensor digitorum longus (EDL) muscles of spinal cord transected (SCT), OEG-transplanted rats eight months after the intervention and compared with non-transplanted SCT-rats and sham-operated (without SCT) controls (C). A multivariate analysis encompassing all the parameters indicated that OEGtransplanted rats displayed skeletal muscle phenotypes intermediate between nontransplanted and sham-operated controls, but different from both. A high correlation was observed between behaviourally-tested sensory-motor functional capacity and expression level of slow- and fast-twitch hind limb skeletal muscle phenotypic markers, particularly the histochemical glycerol-3-phosphate dehydrogenase activity (-0.843, p<0.0001) and the fraction of variant 2s of the slow regulatory myosin light chain isoform (0.848, p<0.0001) in SOL. Despite the mean overall effect of OEG-transplants in patterning skeletal muscle protein expression towards normal, in 6 out of 9 animals they appeared insufficient to overcome fibre type switching and to support a consistent and generalized long-term maintenance of normal skeletal muscle characteristics. The interplay of OEG and exercise-mediated neurotrophic actions is a plausible mechanism underlying OEG-transplantation effects on paralyzed skeletal muscle.