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PubMed1978

Effects of the spinal cord section and of subsequent denervation on the mechanical properties of fast and slow muscles.

The Soleus muscle of the rat, 3--6 months old, becomes significantly faster than in the controls, if the spinal cord is cut at birth. Mechanical properties of Extensor Digitorum Longus (EDL) muscle are not altered by spinal cord section. In cordotomized animals Soleus muscle always remains slower than EDL muscle. Denervation, performed 3--6 months after birth, has the same slowing effects in the Soleus and EDL muscles, both in cordotomized and in the control animals.

Aging↗
PubMed1988

Effects of reinnervation with normal and tetrodotoxin-inactive nerves on resting membrane potential of rat skeletal muscle.

Resting membrane potentials (RMPs) have been recorded in vitro near the end-plate region of rat soleus muscles reinnervated with tetrodotoxin-inactive nerves and compared with those of denervated muscles whose reinnervation had been prevented. The two muscle groups exhibited the same low values of RMP typical of denervated muscles. In control muscles of rats in which impulse conduction was left unimpaired, reinnervation induced the expected increase in RMP values towards normal. It is suggested that, at least for this property, reinnervation restores to normal the muscle fibre membrane essentially through the return of activity.

Animals↗
PubMed1992

[Reinnervation after direct neurotization in cross innervated rats--a study of spinal anterior horn cells by horseradish peroxidase method].

This experiment was performed to clarify the progress of the reinnervation of the denervated muscle after direct neurotization using cross innervation. In this study 79 rats were used. The common peroneal nerve was cut and neurotized into the previously denervated gastrocnemius muscle. At different stages after neurotization, evoked M-waves of the neurotized muscle, and muscle weights were analyzed. Histological findings of the neurotized and denervated gastrocnemius muscles, and the number of spinal anterior horn cells labeled by the horseradish peroxidase method, were also studied. The labeled cells of the neurotized gastrocnemius muscle were located in the spinal level between L3 and L5, which was almost the same site as that of the anterior tibial muscle in normal rats. This finding showed that the denervated gastrocnemius muscle was reinnervated by the implanted common peroneal nerve. The labeled cells of the neurotized gastrocnemius muscle started to appear 2 weeks after neurotization, and the number of cells were almost the same as in the control side from 3 weeks to the end of the experiment. The fixed formed M-wave was observed in some cases 3 weeks after neurotization and in all cases at 6 weeks and thereafter. Four weeks after neurotization and denervation, the weight of neurotized muscle was significantly heavier than that of denervated muscle. The histological findings of the gastrocnemius muscle 3 months after neurotization were almost normal. These results showed that the reinnervation of denervated muscle after direct neurotization using cross innervation began after 2 weeks and the neurotized muscle started to regain its function 3 weeks after the neurotization. The present study also suggested that the muscle power of the neurotized muscle recovered fully resulting from increasing number of labeled spinal anterior horn cells.

Animals↗
PubMed2001

Muscle activity and muscle agrin regulate the organization of cytoskeletal proteins and attached acetylcholine receptor (AchR) aggregates in skeletal muscle fibers.

In innervated skeletal muscle fibers, dystrophin and beta-dystroglycan form rib-like structures (costameres) that appear as predominantly transverse stripes over Z and M lines. Here, we show that the orientation of these stripes becomes longitudinal in denervated muscles and transverse again in denervated electrically stimulated muscles. Skeletal muscle fibers express nonneural (muscle) agrin whose function is not well understood. In this work, a single application of > or = 10 nM purified recombinant muscle agrin into denervated muscles preserved the transverse orientation of costameric proteins that is typical for innervated muscles, as did a single application of > or = 1 microM neural agrin. At lower concentration, neural agrin induced acetylcholine receptor aggregates, which colocalized with longitudinally oriented beta-dystroglycan, dystrophin, utrophin, syntrophin, rapsyn, and beta 2-laminin in denervated unstimulated fibers and with the same but transversely oriented proteins in innervated or denervated stimulated fibers. The results indicate that costameres are plastic structures whose organization depends on electrical muscle activity and/or muscle agrin.

Agrin↗
PubMed1981

Terminal sprouting in rat sternocostalis muscle following partial denervation.

The sternocostalis muscle of the rat was examined at one to five days after partial denervation and levels of terminal sprouting were assessed. The removal of one intercostal nerve caused localised degeneration which did not extend more than a few muscle fibres deep into the field of distribution of the adjacent nerve. Terminal sprouting was clearly seen at 24 h after operation and did not appear to develop further up to five days. There was no difference in the sprouting responses to section of either intercostal nerve 2, 4 or 5. There was, however, a decrease in the response with increasing distance from the cut nerve. No sprouting response was observed in the contralateral muscle. Comparison of sprouting levels of B and C type end plates revealed a greater percentage of C type end plates with sprouts. However, the response of B type end plates, considered in relation to the levels of spontaneous sprouting, was greater than that of C type end plates.

Animals↗
PubMed1997

[Motor reconnection between the damaged cervical cord and the denervated biceps muscle using an autologous peripheral nerve segment in the adult marmoset].

Our research group is studying, in the primate (marmoset), the conditions of an anatomical and functional reconstruction of the spinal cord and of its motor connections, following a focal spinal lesion. In this attempt to repair the damaged neuronal circuitry, we used long segments of autologous peripheral nerves joining the injured cervical spinal cord to an aneural region of the denervated biceps brachialis muscle (7 marmosets) or to the musculocutaneous nerve (6 marmosets). After retrograde tracing (HRP) and histochemical studies of the muscle, we found that a great number of neurons, located mostly in the ventral part of the grey matter extended axons into the peripheral nerve graft. Some of these labelled neurons were motoneurons, which could established functionnal neuromuscular junctions. The muscle regeneration was effective but slower than already known in rat studies.

Animals↗
PubMed1989

Decrease in neuronal uptake of noradrenaline simply explains the supersensitivity after sympathectomy in the rat iris dilator.

The effect of superior cervical ganglionectomy or long term treatment with guanethidine on the mechanical response of dilator muscle of the rat iris to several stimulants was examined. The dose-response curve for noradrenaline (NA) was significantly shifted to the left 7 days after denervation (ca. x 10) or by treatment with guanethidine (ca. x 10), but those for methoxamine (Meth) and acetylcholine (ACh) were not. Cocaine did not further sensitize the denervated muscle to NA, but it sensitized the normal muscle to an extent similar to that caused by denervation. Cocaine did not affect the sensitivity to Meth in both control and denervated muscles. The maximum response to NA decreased by about 30% or 20% after surgical or chemical denervation, respectively, while those to Meth, ACh and Ca2+ did not alter significantly. These results indicate that in the dilator muscle, the sympathetic denervation caused a purely specific supersensitivity to NA which was simply explained by a presynaptic mechanism: an impairment of the neuronal uptake process.

Acetylcholine↗
PubMed1999

Enhanced tendon healing with GDF 5 and 6.

Between ruptured tendon ends, undifferentiated mesenchymal cells invade the hematoma and differentiate to form a tendon regenerate. This differentiation is partly directed by mechanical stimuli, which are difficult to apply and control clinically. For example, closed treatment of Achilles tendon ruptures is associated with a risk of rerupture of the regenerate. Improved tendon healing by exogenous growth factors has not previously been reported. Three proteins in the Bone Morphogenetic Protein (BMP) family--namely Growth and Differentiation Factors (GDFs) 5, 6 and 7--have recently been shown to induce a tendon- or ligament-like tissue after intramuscular implantation in rats, indicating a new way to improve tendon healing. We transected the Achilles tendon in 66 rats and denervated the calf muscle. Denervation served to reduce the mechanical stimulation to the tendon callus by eliminating muscle contractions. GDF 5 or 6 were implanted on collagen sponges in the tendon defects in two doses and compared to collagen sponges alone. The rats were killed after 2 weeks and the tensile strength of the tendon regenerate was found to be increased by both proteins in a seemingly dose-dependent manner.

Achilles Tendon↗
PubMed1991

Effects of insulin and phospholipase C in control and denervated rat skeletal muscle.

Phospholipase C (PLC), an enzyme that increases endogenous 1,2-diacylglycerol (DAG), caused dose-dependent stimulation of 2-deoxy-D-glucose (2-DG) uptake in rat soleus muscles; the maximal effect was less than that of insulin. In denervated muscles the effect of insulin on 2-DG uptake was markedly reduced, whereas the response to PLC was identical to that of control muscles. Both PLC and insulin stimulated glucose incorporation into glycogen in control but not in denervated solei. Amino acid transport was unaffected by PLC; however, the enzyme completely inhibited the stimulation of amino acid transport by insulin. PLC did not activate the insulin receptor tyrosine kinase but decreased activation of the receptor by insulin in vivo. Basal muscle DAG content increased after denervation. Incubation with PLC markedly increased DAG in control and in denervated muscle. Insulin increased total DAG mass less than PLC in control muscles and did not affect DAG in denervated muscles. In media without added Ca2+, PLC stimulation of DAG production was impaired, and 2-DG uptake was unresponsive to PLC. The data are consistent with, but do not prove, that a subpopulation of DAGs may participate in insulin-mediated stimulation of glucose transport. They also suggest that the denervation-induced insulin resistance of glucose transport may reflect impaired generation of certain DAGs involved in the signaling cascade.

Animals↗
PubMed1983

Muscle pyruvate oxidation following denervation and reinnervation.

Muscle pyruvate metabolism was studied in rats following sciatic nerve crush. Control studies showed high pyruvate dehydrogenase and lipoamide dehydrogenase enzyme activity in muscle with type 1 fiber predominance (soleus) and low activities in muscle with type 2 fiber predominance (extensor digitorum longus), whereas lactate dehydrogenase was much higher in the latter. Following denervation, both muscles showed a significant reduction in pyruvate dehydrogenase enzyme activity. During reinnervation, muscle with type 2 predominance developed significantly elevated pyruvate oxidation enzyme activities.

Animals↗
PubMed1994

Elevated insulin-like growth factor (IGF) gene expression in sciatic nerves during IGF-supported nerve regeneration.

Nerve regeneration is augmented by neurotrophic activity, which has long been known to be increased in lesioned nerves. Of identified soluble nerve-derived neurotrophic factors, to date only insulin-like growth factors (IGFs) have been observed to increase the rate of axon regeneration in peripheral nerves. We report that IGF-I and IGF-II mRNA contents were significantly increased (P < 0.0005) distal to the site of crush in rat sciatic nerves, and decreased following axon regeneration. In transected nerves in which axon regeneration was prevented, IGF mRNAs remained elevated. IGF-I mRNAs per mg tissue were increased more in lesioned nerves than denervated muscles, whereas IGF-II mRNAs were increased more in denervated muscles than lesioned nerves. This suggested that IGF-I and IGF-II each play distinct regulatory roles during regeneration. These data bolster the hypothesis that increased IGF mRNA content in nerves supports the rate of nerve regeneration in mammals.

Animals↗
PubMed2001

Effects of purified recombinant neural and muscle agrin on skeletal muscle fibers in vivo.

Aggregation of acetylcholine receptors (AChRs) in muscle fibers by nerve-derived agrin plays a key role in the formation of neuromuscular junctions. So far, the effects of agrin on muscle fibers have been studied in culture systems, transgenic animals, and in animals injected with agrin--cDNA constructs. We have applied purified recombinant chick neural and muscle agrin to rat soleus muscle in vivo and obtained the following results. Both neural and muscle agrin bind uniformly to the surface of innervated and denervated muscle fibers along their entire length. Neural agrin causes a dose-dependent appearance of AChR aggregates, which persist > or = 7 wk after a single application. Muscle agrin does not cluster AChRs and at 10 times the concentration of neural agrin does not reduce binding or AChR-aggregating activity of neural agrin. Electrical muscle activity affects the stability of agrin binding and the number, size, and spatial distribution of the neural agrin--induced AChR aggregates. Injected agrin is recovered from the muscles together with laminin and both proteins coimmunoprecipitate, indicating that agrin binds to laminin in vivo. Thus, the present approach provides a novel, simple, and efficient method for studying the effects of agrin on muscle under controlled conditions in vivo.

Agrin↗
PubMed1971

Induction of the action potential mechanism in slow muscle fibres of the frog.

1. The electrical and structural characteristics of ;slow' muscle fibres of the frog were studied in normal and denervated muscles, and in muscles undergoing re-innervation by a mixed nerve containing large and small motor axons.2. In agreement with previous studies, slow fibres in normally innervated muscles were incapable of producing action potentials.3. Approximately 2 weeks after the sciatic nerve was transected or crushed, slow muscle fibres acquired the ability to generate action potentials. These fibres were positively identified as belonging to the slow type, because their passive-electrical and ultrastructural characteristics remained essentially unchanged after the operations.4. The action potential mechanism induced in slow fibres is sodium-dependent, and is blocked by tetrodotoxin.5. After long-term re-innervation by a mixed nerve, slow fibres lose their acquired ability to generate action potentials, presumably because small motor axons re-establish connexion with the fibres.6. It is concluded that the action potential mechanism of slow muscle fibres is under neural control, and is normally suppressed by small motor axons.

Action Potentials↗