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J Physiol Volume 586, Number 10, 2593-2610, May 15, 2008 DOI: 10.1113/jphysiol.2007.149120
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SKELETAL MUSCLE AND EXERCISE

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

 Pilar Negredo1, José-Luis L. Rivero2, Beatriz González1, Almudena Ramón-Cueto3 and Rafael Manso1

1 Centre of Molecular Biology ‘Severo Ochoa’ (CSIC-UAM), Autonomous University of Madrid, E-28049 Cantoblanco, Madrid, Spain
2 Laboratory of Muscular Biopathology, Department of Comparative Anatomy and Pathological Anatomy, Faculty of Veterinary Science, University of Cordoba, E-14014 Cordoba, Spain
3 Neural Regeneration Laboratory, Institute of Biomedicine (CSIC), E-46010 Valencia, Spain

Paralysed 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 morphological, metabolic and molecular markers were assessed in soleus (SOL) and extensor digitorum longus (EDL) muscles of spinal cord transected (SCT), OEG-transplanted rats 8 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 OEG-transplanted rats displayed skeletal muscle phenotypes intermediate between non-transplanted 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 paralysed skeletal muscle.

(Received 3 December 2007; accepted after revision 27 March 2008; first published online 27 March 2008)
Corresponding author R. Manso: Departamento de Biología Molecular, Facultad de Ciencias, Universidad Autónoma de Madrid, E-28049 Cantoblanco, España. Email: rafael.manso{at}uam.es






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