Myotrophic effects on denervated fast-twitch muscles of mice: Correlation of physiologic, biochemical, and morphologic findings

Davis, Heather L.; Bressler, Bernard; Jasch, Laura G.

doi:10.1016/0014-4886(88)90164-1

Cited by 8 publications

(4 citation statements)

References 24 publications

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“…However, we did observe subtle differences in MHC expression between treatments, suggesting a minor role for nerve-derived chemicals in the regulation of this protein. The lack of changes in the order observed in studies where the administration of trophic substances attenuated certain denervation-like changes upon myofibrillar proteins may be reconciled by the fact that in these reports the effect may have been related to the high systemic concentrations of these exogenous substances [28,29].…”

Section: Discussionmentioning

confidence: 99%

“…Comparison of these two models of complete disuse also provided insight into the relative contribution of nerve-evoked activity and putative chemical factors on the expression of these proteins, since during TTX paralysis, axon transport and the integrity of synaptic contacts are maintained [8,23,24]. Such an assessment appears timely since the extent to which trophic mechanisms influence myofibrillar proteins remains equivocal [14,[25][26][27][28][29].…”

Section: Introductionmentioning

confidence: 99%

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Regulation of myosin heavy chain expression in adult rat hindlimb muscles during short‐term paralysis: comparison of denervation and tetrodotoxin‐induced neural inactivation

1996

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The extent to which myosin profiles within aduR fast and slow muscles are altered by short-term paralysis remains equivocal. We used an array of specific antibodies to identify adult and developmental MHC isoforms within EDL and soleus muscle fibers, and show a marked multiple expression of MHCs with a general shift towards slower and more energy efficient MHC profiles after 2 weeks of denervation or TTX nerve conduction block. Paralysis also induced marked expression of an embryonic MHC within most EDL cell types, and a subtle, paralysis-sensitive, expression of ¢x-cardiac MHC within speeific EDL and soleus extrafusal fibers. Comparison of treatment groups also permitted assessment of the relative influence of neural activity versus trophic factors on these isoforms, and confirmed activity as a major, but not sole, regulator of MHC expression.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Regulation of myosin heavy chain expression in adult rat hindlimb muscles during short‐term paralysis: comparison of denervation and tetrodotoxin‐induced neural inactivation

1996

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“…1997b) showing that significant recovery of muscle mass and type 2b muscle fibre diameter was undetectable before 120 days postsurgery. Increases in NMJ size observed in the EDL of NT‐3‐treated rats appears therefore to be linked with increased muscle fibre size which in turn implies a functional benefit in terms of increased force generation (Davis et al . 1988).…”

Section: Discussionmentioning

confidence: 99%

Differential effects of NT‐3 on reinnervation of the fast extensor digitorum longus (EDL) and the slow soleus muscle of rat

Simon

Terenghi

Green

et al. 2000

Eur J of Neuroscience

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Previous studies of gastrocnemius muscle reinnervation showed specific normalization of the proportion and diameter of fast type 2b muscle fibres following NT-3 delivery to the proximal stump of the cut sciatic nerve. Here, we investigate if normalization was related to greater improvement of muscle reinnervation of fast (extensor digitorum longus; EDL) than slow (soleus) motor units. NT-3-impregnated (NT-3 group) or plain fibronectin (FN group) mats were inserted into a sciatic nerve gap. Neuromuscular junctions (NMJs) labelled with TRITC-alpha-bungarotoxin were colabelled with calcitonin gene-related peptide (CGRP) or 4E2 antisera and imaged using confocal microscopy. CGRP and 4E2 were used as markers for newly reinnervated and structurally mature NMJs, respectively. At 40 days postsurgery, denervated NMJs in EDL and soleus muscles of both groups presented a 50% decrease of surface area due to decreased width. At day 80 in EDL, more NMJs were reinnervated by CGRP-immunoreactive terminals in the NT-3 (7.1%) than in the FN group (4.2%); there was no difference between groups for soleus. At 120 days, 4E2-immunoreactive NMJs were more numerous in EDL of the NT-3 (40.0%) than in the FN group (7.3%), unlike in soleus (NT-3, 1. 6%; FN, 1.8%), and presented a partial size recovery. These results indicate that NT-3 preferentially improves reinnervation of fast muscles over slow muscle, although the mechanism of this improvement is still unclear.

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“…This result is strongly indicative that NT-3 applied to the cut nerve may influence the regeneration of a physiologically distinct subset of motor neurons supplying type 2b muscle fibers. While functional assessment of NT-3–enhanced reinnervated muscles has yet to be performed, it is known that for reinnervated muscle, as in normal muscle, force generated is proportional to cross-sectional area of muscle fibers ( Schantz et al, 1983 ; Davis et al, 1988 ; Totosy de Zepetnek et al, 1992 ) and increase in diameter and proportion of 2b fibers seen in the NT group is likely to result in increased force generation.…”

Section: Discussionmentioning

confidence: 99%

Neurotrophin-3–enhanced Nerve Regeneration Selectively Improves Recovery of Muscle Fibers Expressing Myosin Heavy Chains 2b

Sterne

Coulton

Brown

et al. 1997

The Journal of Cell Biology

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The purpose of this study was to evaluate the effect of neurotrophin 3 (NT-3) enhanced nerve regeneration on the reinnervation of a target muscle. Muscle fibers can be classified according to their mechanical properties and myosin heavy chain (MHC) isoform composition. MHC1 containing slow-type and MHC2a or 2b fast-type fibers are normally distributed in a mosaic pattern, their phenotype dictated by motor innervation. After denervation, all fibers switch to fast-type MHC2b expression and also undergo atrophy resulting in loss of muscle mass. After regeneration, discrimination between fast and slow fibers returns, but the distribution and fiber size change according to the level of reinnervation. In this study, rat gastrocnemius muscles (ipsilateral and contralateral to the side of nerve injury) were collected up to 8 mo after nerve repair, with or without local delivery of NT-3. The phenotype changes of MHC1, 2a, and 2b were analyzed by immunohistochemistry, and fiber type proportion, diameter, and grouping were assessed by computerized image analysis. At 8 mo, the local delivery of NT-3 resulted in significant improvement in gastrocnemius muscle weight compared with controls (NT-3 group 47%, controls 39% weight of contralateral normal muscle; P < 0.05). NT-3 delivery resulted in a significant increase in the proportion (NT-3 43.3%, controls 35.7%; P < 0.05) and diameter (NT-3 87.8 μm, controls 70.8 μm; P < 0.05) of fast type 2b fibers after reinnervation. This effect was specific to type 2b fibers; no normalization was seen in other fiber types.This study indicates that NT-3–enhanced axonal regeneration has a beneficial effect on the motor target organ. Also, NT-3 may be specifically affecting a subset of motoneurons that determine type 2b muscle fiber phenotype. As NT-3 was topically applied to cut nerves, our data suggest a discriminating effect of the neurotrophin on neuro–muscular interaction. These results would imply that muscle fibers may be differentially responsive to other neurotrophic factors and indicate the potential clinical role of NT-3 in the prevention of muscle atrophy after nerve injury.

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Myotrophic effects on denervated fast-twitch muscles of mice: Correlation of physiologic, biochemical, and morphologic findings

Cited by 8 publications

References 24 publications

Regulation of myosin heavy chain expression in adult rat hindlimb muscles during short‐term paralysis: comparison of denervation and tetrodotoxin‐induced neural inactivation

Regulation of myosin heavy chain expression in adult rat hindlimb muscles during short‐term paralysis: comparison of denervation and tetrodotoxin‐induced neural inactivation

Differential effects of NT‐3 on reinnervation of the fast extensor digitorum longus (EDL) and the slow soleus muscle of rat

Neurotrophin-3–enhanced Nerve Regeneration Selectively Improves Recovery of Muscle Fibers Expressing Myosin Heavy Chains 2b

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