Regeneration of Reinnervated Rat Soleus Muscle Is Accompanied by Fiber Transition Toward a Faster Phenotype

Abstract

S U M M A R Y The functional recovery of skeletal muscles after peripheral nerve transection and microsurgical repair is generally incomplete. Several reinnervation abnormalities have been described even after nerve reconstruction surgery. Less is known, however, about the regenerative capacity of reinnervated muscles. Previously, we detected remarkable morphological and motor endplate alterations after inducing muscle necrosis and subsequent regeneration in the reinnervated rat soleus muscle. In the present study, we comparatively analyzed the morphometric properties of different fiber populations, as well as the expression pattern of myosin heavy chain isoforms at both immunohistochemical and mRNA levels in reinnervated versus reinnervated-regenerated muscles. A dramatic slow-tofast fiber type transition was found in reinnervated soleus, and a further change toward the fast phenotype was observed in reinnervated-regenerated muscles. These findings suggest that the (fast) pattern of reinnervation plays a dominant role in the specification of fiber phenotype during regeneration, which can contribute to the long-lasting functional impairment of the reinnervated muscle. Moreover, because the fast II fibers (and selectively, a certain population of the fast IIB fibers) showed better recovery than did the slow type I fibers, the faster phenotype of the reinnervated-regenerated muscle seems to be actively maintained by selective yet undefined cues. (J Histochem Cytochem 56:111-123, 2008)

Effects of nandrolone on recovery after neurotization of chronically denervated muscle in a rat model

“…31,42 This slow to fast fiber transition is typically maintained following reinnervation. 33 We did not see a significant shift from Type I to Type II fibers, but among Type II fibers there was a shift toward Type IIa for both the 3-and 6-month denervation groups.…”

Improvement of Contraction Force in Injured Skeletal Muscle after Autologous Mesenchymal Stroma Cell Transplantation Is Accompanied by Slow to Fast Fiber Type Shift

“…According to Mendler et al [25], it could also be possible that an initial cross-innervation leads to a persistence of the observed fast fiber type shift.…”

“…Following cross-re-innervation (i.e., innervation of slowMHC fibers with ‘fast' motor neurons and innervation of fastMHC fibers with ‘slow' motor neurons), slowMHC fibers tend to express fastMHC and vice versa [19]. Mendler et al [25] found a slow-to-fast fiber type transition in re-innervated soleus and could show a persistent change towards a fastMHC phenotype in regenerated muscles. In contrast, Maatsura et al [17] observed a fastMHC to slowMHC fiber type shift 2 weeks after the trauma, which persisted thereafter.…”

Regeneration of skeletal muscle

“…In the rat soleus muscle, this rapid maturation of myotubes coincides with a switch from expression of embryonic to neonatal myosin heavy chains to adult myosin (Whalen et al 1990). While this change is independent of nerve function, Mendler et al (2008) have shown that, following dennervation and reinnervation, muscle fibers switch from slow-type fibers to fast-type fibers following reinnervation of the muscle fibers (Mendler et al 2008). Furthermore, Gregorevic et al (2004) have demonstrated that these regenerating fibers adopt their fast and slow twitch properties as they regenerate (Gregorevic et al 2004).…”