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PubMed1980

Effects of denervation and botulinum toxin on muscle sensitivity to acetylcholine and acceptance of foreign innervation in the frog.

1. The effects of denervation and local paralysis produced by botulinum toxin (type D) on the sensitivity of skeletal muscle to ACh and its ability to accept innervation by an implanted foreign nerve were investigated in the frog. 2. Denervated muscles developed supersensitivity to ACh within 2 weeks and became extensively innervated by an implanted foreign nerve after about 4 weeks. 3. Chronic electrical stimulation of denervated muscles (50 Hz for 1 sec every 60 sec) did not prevent the development of supersensitivity. 4. Muscles paralysed by botulinum toxin did not usually develop supersensitivity to ACh until after 2-3 months and the extra-junctional sensitivity of individual fibres was generally less than after denervation. Significant innervation of the paralysed muscles by an implanted foreign nerve did not occur until after 2-3 months. 5. The results suggest that in the frog nerves are able to control muscle sensitivity to ACh and to prevent innervation by foreign nerves by some mechanism other than muscle activity. Prolonged inactivity seems to result in some development of extra-junctional sensitivity and acceptance of foreign innervation.

Acetylcholine↗
PubMed2006

Differential gene expression in the developing mouse ureter.

In many instances, kidney dysgenesis results as a secondary consequence to defects in the development of the ureter. Through the use of mouse genetics a number of genes associated with such malformations have been identified, however, the cause of many other abnormalities remain unknown. In order to identify novel genes involved in ureter development we compared gene expression in embryonic day (E) 12.5, E15.5 and postnatal day (P) 75 ureters using the Compugen mouse long oligo microarrays. A total of 248 genes were dynamically upregulated and 208 downregulated between E12.5 and P75. At E12.5, when the mouse ureter is comprised of a simple cuboidal epithelium surrounded by ureteric mesenchyme, genes previously reported to be expressed in the ureteric mesenchyme, foxC1 and foxC2 were upregulated. By E15.5 the epithelial layer develops into urothelium, impermeable to urine, and smooth muscle develops for the peristaltic movement of urine towards the bladder. The development of these two cell types coincided with the upregulation of UPIIIa, RAB27b and PPARgamma reported to be expressed in the urothelium, and several muscle genes, Acta1, Tnnt2, Myocd, and Tpm2. In situ hybridization identified several novel genes with spatial expression within the smooth muscle, Acta1; ureteric mesenchyme and smooth muscle, Thbs2 and Col5a2; and urothelium, Kcnj8 and Adh1. This study marks the first known report defining global gene expression of the developing mouse ureter and will provide insight into the molecular mechanisms underlying kidney and lower urinary tract malformations.

Animals↗
PubMed1999

BDM (2,3-butanedione monoxime), an inhibitor of myosin-actin interaction, suppresses myofibrillogenesis in skeletal muscle cells in culture.

During the initial phase of myofibrillogenesis in developing muscle cells, the majority of thin filaments lie parallel to, and exhibit correct polarity and spatial position with thick filaments, as in mature myofibrils. Since myosin is known to function as an accelerator of actin polymerization in vitro, it has been postulated that myosin-actin interaction is important in the initial phase of myofibrillogenesis. To clarify further the role of actin-myosin interaction in myofibril formation during development, BDM (2, 3-butanedione 2-monoxime), an inhibitor of myosin ATPase, was applied to primary cultures of skeletal muscle to inhibit myosin activity during myofibrillogenesis, and myofibril formation was examined. When 10 mM BDM was added to the myotubes just after fusion and the cultures were maintained for a further 4 days, cross-striated myofibrils were scarcely observed by fluorescence microscopy when examined by staining with antibodies to actin, myosin, troponin and alpha-actinin, whereas in the control myotubes not exposed to BDM, typical sarcomeric structures were detected. Electron microscopy revealed a disorganized arrangement of myofilaments and incomplete sarcomeric structures in the BDM-treated myotubes. Thus, formation of cross-striated myofibrils was remarkably suppressed in the BDM-treated myotubes. When the myotubes cultured in BDM-containing media were transferred to control media, sarcomeric structures were formed in 2-3 days, suggesting that the inhibitory effect of BDM on myotubes is reversible. These results suggest that actin-myosin interaction plays a critical role in the early process of myofibrillogenesis.

Actins↗
PubMed2000

The effect of muscle transplantation after unilateral partial facial paralysis on craniofacial growth and development: relationship between muscle and nerve histomorphometric findings.

Muscle transplantation has become an indispensable tool to restore the smile in patients with long-standing or congenital facial paralysis. However, little is known of the effect of this surgical intervention on craniofacial growth and development or of the adaptation of the transplant to its recipient site under circumstances of growth. The present study investigates these phenomena in the rabbit model. Twelve-day-old New Zealand White rabbits were randomly assigned to three experimental groups. The control group was used to study normal craniofacial growth and development (n = 15). In the nerve ablation group, unilateral paralysis of the buccal branches of the facial nerve was surgically induced (n = 15). In the transplant group, the surgically induced unilateral paralysis of the buccal branches was immediately followed by a neuromuscular graft (n = 12). All animals were operated on at the age of 12 days, and follow-up evaluations were performed at the ages of 2 months and 6 months. Computerized dorsoventral roentgencephalometric and computed tomography investigations were performed at both ages. Nerve and muscle histomorphometric measurements were performed at the age of 6 months to relate the quality of nerve and muscle regeneration to the growth parameters. The roentgencephalometric measurements revealed that analogous disturbed parameters were present in the nerve ablation and the transplant groups. However, in the transplant group, an additional significant effect of time between 2 and 6 months was seen for some parameters. This resulted in significant differences between the nerve ablation and transplant groups at 6 months for these parameters. Computed tomography measurements showed no significant differences in maxillary or mandibular volume in the transplant group compared with the control or nerve ablation groups. However, a significantly diminished increase in bone volume existed in the transplant group for the time period between 2 and 6 months in comparison with the control and nerve ablation groups. Muscle histomorphometric findings revealed a significant change in muscle fiber composition in the graft compared with the normal latissimus dorsi muscle; this was due to a major decrease in type IIB fibers, with an increase in type I and type IIA fibers. Compared with the normal zygomaticoauricular muscle, the amount of type I fibers was significantly increased. No fiber atrophy was found. Macroscopically, the transplanted muscle failed to increase its length during growth. Nerve histomorphometric findings demonstrated a normal amount of nerve fibers; however, they had significantly decreased diameters and reduced myelin areas. The nerve histomorphometric parameters were related to the muscle histomorphometric findings, which in turn were related to craniofacial growth disturbances. These findings suggested that the main growth differences between the transplant group and the control group may have been due to altered nerve function influencing muscle function. Scar tissue formation and the development of more intense muscle activity later are suggested as the causes of the additional effect of time between 2 and 6 months for the several parameters in the transplant group. Reasons for the failure of complete conversion of the graft to a fast muscle and the failure of the transplant to elongate during growth are discussed.

Animals↗
PubMedDate not supplied

Metabolic transitions in rat jaw muscles during postnatal development.

The program of acquisition of adult metabolic phenotypes was studied in three jaw muscles in order to determine the link between muscle metabolism and functional development. During early postnatal stages, there were similar transitions in the masseter, anterior digastric, and internal pterygoid muscles with respect to fiber growth, fiber type composition, and whole muscle energy metabolism. Oxidative capacity, as judged by the activities of the enzymes succinate dehydrogenase (SDH), malate dehydrogenase (MDH), and beta-hydroxyacyl CoA dehydrogenase (beta OAC), rose sharply after birth to reach near maximal levels by 3 weeks. The capacities for glycolytic metabolism represented by lactate dehydrogenase (LDH), and for high-energy phosphate metabolism represented by adenylokinase (AK) and creatine kinase (CK) activities, rose gradually, not reaching peak values until 6 weeks or later. Thus, the maturation of oxidative metabolism preceded that of glycolytic metabolism in the developing jaw muscles. This was documented for individual fibers in the masseter muscle. Differential metabolic maturation among the jaw muscles was evident beyond 3 weeks. All three jaw muscles attained their specific adult fiber-type profile by about 6 weeks. This maturation program differed from that of hindlimb muscles [Nemeth et al., J Neurosci 9:2336-2343, 1989] and diaphragm muscle [Kelly et al., J Neurosci 11:1231-1242, 1991], reflecting their differential energy demands for contractile performance.

Animals↗
PubMed1994

The influence of maternal nutrition on muscle fiber number development in the porcine fetus and on subsequent postnatal growth.

In the pig, undernutrition in utero causes low birth weight, a decrease in muscle fiber number, and a reduction in postnatal growth rate. The effect on fiber number is mediated via a reduced secondary fiber population. Within a litter of pigs, lighter-weight pigs have probably suffered some deficit in muscle fiber number. In an attempt to improve the number of fibers in the lighter-weight pig fetuses, four maternal feeding regimens were used, one serving as the control. Maternal feed intake was doubled for one of three time periods during pregnancy: 1) d 25 to 50 (HE) immediately before fiber hyperplasia; 2) d 50 to 80 (HL) during fiber hyperplasia; or 3) d 25 to 80 (HT) covering both developmental events. Controls were fed at levels routinely used for pregnant sows on the farm. Sows farrowed normally and pig birth weights were recorded. Estimates were made of total myofiber number, total primary fiber number, and mean secondary:primary fiber number ratio (S:P) for the semitendinosus of each pig at 5 wk postnatal or 80 kg (HT and two control litters only). The progeny of all supplemented sows had a significantly greater mean S:P ratio (P < .05), and the HE pigs tended to have a greater number of muscle fibers than control pigs (403,840 +/- 8,197 vs 370,970 +/- 12,720). Postnatal growth rate to 80 kg was also investigated for the HT group of pigs.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1998

Development of the avian iris and ciliary body: the role of activin and follistatin in coordination of the smooth-to-striated muscle transition.

Although general principles have been established in the regulation of vetebrate organogenesis, the specific molecules responsible for such signaling are just being identified. We have studied differentiation in the avian iris and ciliary body which undergoes a transition from smooth to striated muscle. Using heterochronic cocultures, we have found that striated muscle differentiation in pretransition (E8) cells is induced by midtransition (E11) cells through a secreted and soluble activity. In addition, contact-mediated mechanisms among pretransition cells prevented precocious striated muscle differentiation. We have tested the role of activin and its antagonist follistatin, as candidate regulators of this muscle transition. Activin induced smooth muscle differentiation while repressing striated muscle development. Conversely, follistatin promoted the emergence of striated muscle, while inhibiting smooth muscle differentiation. Significantly, secreted follistatin activity was found to increase during the smooth-to-striated muscle transition. Moreover, the striated muscle inducing activity from midtransition iris and ciliary body cell conditioned medium was depleted with an activin-affinity column which binds follistatin. These results suggest that activin and follistatin coordinate differentiation in the avian iris and ciliary body.

Activins↗
PubMed1994

[Cell adhesion and development of skeletal muscle].

Cell adhesion is a cell autonomous property of pluricellular organisms at the basis of tissues and organs formation. Thus, adhesive processes must be considered as key features of the development of skeletal muscle as well as of other tissues. We present here the actual knowledge on cell adhesion molecules in skeletal muscle morphogenesis. The spatio-temporal expression patterns of N-CAM, N-cadherin, M-cadherin, VLA-4 and VCAM-1 during chicken and mouse myogenesis suggest that these cell adhesion molecules are differentially involved in myoblast-myoblast, myoblast-myotube and myotube-myotube interactions. These molecules link myogenic cells before they are separated by their basal laminae. They can potentially induce preferential cell adhesion and sorting-out as it has been described by Holtfreter. This differential adhesion may lead either to myoblast fusion or to preferential association between primary and secondary myotubes.

Animals↗
PubMed2001

Fatal rhabdomyolysis after acute sodium monensin (Rumensin) toxicity: case report.

Myoglobinuria or rhabdomyolysis occurs when myoglobin escapes into the blood and then into the urine after acute muscle necrosis. It can be a serious medical condition leading to renal failure and death. There are many causes including exertion, crush syndromes, ischaemia, metabolic disorders, exogenous toxins and drugs, heat stroke and hereditary disorders such as malignant hyperthermia. We report the case of a 17 year-old boy who developed myoglobinuria, renal failure and death 11 days after ingesting sodium monensin, possibly with the intention of developing muscles. Sodium monensin, the active principle of Rumensin(R), is a dietary additive used as a growth promoter for confined cattle. There are no previous reports of human intoxication. Accidental or experimental sodium monensin intoxication in animals produces similar findings to those seen in this case.

Acute Disease↗
PubMed2026

Muscular fiber properties and multi-omics investigation of larval and adult locomotor muscle in Microhyla fissipes.

During metamorphosis, Microhyla fissipes undergoes a critical transition from an aquatic to a terrestrial lifestyle, accompanied by significant remodeling of skeletal muscle. Notably, larval tail muscle degenerates, while adult hindlimb muscle develops. However, the molecular mechanisms that orchestrate these muscle type-specific adaptations to the changing environment remain unclear. In this study, histological observation, transcriptomics, and metabolomics were integrated to compare locomotor muscles from two stages: larval muscle from tail versus adult muscle from hindlimb. Our results revealed that adult muscle fibers exhibited reduced diameter and shorter sarcomere length compared to those of tadpoles. Transcriptomic analysis identified 4103 differentially expressed genes (DEGs), including 2182 up-regulated and 1921 down-regulated genes. Up-regulated genes were mainly involved in energy metabolism and cellular homeostasis pathways, including PPAR signaling and oxidative phosphorylation, whereas down-regulated genes were associated with carbohydrate metabolism and cell proliferation pathways, such as glycolysis/gluconeogenesis and PI3K-Akt signaling. Metabolic profiling indicated a metabolic shift from anaerobic to aerobic energy production, with 57 differential metabolites identified, mainly involved in protein metabolism and insulin-related pathways. Integrated multi-omics analysis further highlighted the AMPK and FoxO signaling pathways play key roles in this process. In conclusion, our findings demonstrate that the metabolic and structural differences between larval and adult skeletal muscles are mediated by AMPK- and FoxO-dependent signaling pathways, providing novel insights into the molecular mechanisms underlying adaptive development and locomotor transition in anuran amphibians.

Animals↗
PubMed2006

Activity-dependent gene regulation in skeletal muscle is mediated by a histone deacetylase (HDAC)-Dach2-myogenin signal transduction cascade.

Muscle activity contributes to muscle development and function largely by means of regulated gene expression. Many genes crucial to neuromuscular synapse formation, such as MuSK and nAChRs, are induced before muscle innervation or after muscle denervation, and this induction requires expression of the E-box binding, basic helix-loop-helix muscle-specific transcription factor, myogenin (Mgn). The mechanism by which muscle activity is coupled to gene expression is poorly defined. Here we report that inhibition of histone deacetylase (HDAC) activity attenuates the induction of activity-regulated genes in aneural myotubes and adult denervated muscle. The effect of HDAC inhibitors requires new protein synthesis, suggesting HDACs may regulate the expression of a Mgn transcriptional repressor. We identified Dach2 as a Mgn transcriptional repressor whose expression is dramatically reduced in an HDAC-dependent manner in developing aneural myotubes or adult denervated muscle. Dach2 overexpression in denervated muscle suppressed Mgn, nAChR, and MuSK gene induction, whereas Dach2 knockdown induced Mgn gene expression in innervated muscle and relieved Mgn promoter inhibition by HDAC inhibitors. Thus, a HDAC-Dach2-myogenin signaling pathway has been identified to decode nerve activity and control muscle gene expression in developing and adult skeletal muscle.

Animals↗
PubMed1980

Development of excitatory innervation in the lobster claw closer muscle.

The development of excitatory innervation to the claw closer muscles of 1st (larval), 4th (juvenile), and adult stage lobster was examined by thin serial section electron microscopy. This was possible since neuromuscular terminals of the excitatory axon are distinguishable from those of the inhibitory axon by the shape of their synaptic vesicles in all three stages. In the adult cutter claw closer muscle, innervation of a dorsal and a ventral fiber which is supplied by the fast closer excitor (FCE) and slow closer excitor (SCE) axons respectively, was qualitatively as well as quantitatively similar. Consequently no attempt was made to distinguish between innervation by FCE and SCE axons in the subsequent analysis of 1st, 4th, and adult stage claw closer muscles. Excitatory innervation in the 1st larval stage is limited to four discrete locations in the entire cross-sectional area of the closer muscle. It subsequently spreads to each individual muscle fiber in the adult, thus demonstrating the tremendous proliferation of innervation during development. Concomitantly the mean size of synapses increases significantly from the 1st stage to the 4th stage to the adult lobster. This increase in synaptic size may occur by both the fusion and enlargement of existing smaller synapses. In contrast, the mean size of presynaptic dense bars and their mean number per synapse remained fairly constant in each of the 1st, 4th, and adult stages. However, a relatively greater proportion of adult synapses possessed two or more dense bars compared to their larval and juvenile counterparts. Development of innervation of the lobster claw closer muscle therefore consists of a substantial proliferation of axonal tissue and enlargement of synaptic size.

Animals↗
PubMed2003

Nerve growth factor expression in human dystrophic muscles.

Nerve growth factor (NGF) is a neurotrophin that is expressed during muscle development and is also capable of favoring muscle regeneration in experimental studies. The presence of NGF in muscular dystrophies, such as Duchenne and Becker muscular dystrophies, has never been fully explored. By means of immunohistochemistry, we show that regenerating muscle fibers from such patients consistently express NGF, as do myofibroblasts and mast cells. By contrast, rest fibers from dystrophic patients, as well as muscle fibers from healthy, control patients and even regenerative muscle fibers in polymyositis do not show NGF immunoreactivity. The paracrine effect of NGF on muscle regeneration, as well as its chemoattractant capacities for mast cells, may contribute to explaining why regenerating fibers most frequently occur in clusters and why mast cells are more numerous in dystrophic muscles. Moreover, being a mediator of wound healing and tissue fibrosis, NGF may contribute to long-term muscle regeneration impairment by tissue fibrosis in the muscular dystrophies.

Biopsy↗
PubMed1976

Electron microscopic study of extraocular muscles in myotonic dystrophy.

The extraocular muscles of two middle-aged men with ophthalmoplegia secondary to myotonic dystrophy were studied by electron microscopy. The main change was disorganization in the arrangement of myofibrils rather than degeneration of the cells. Diseased muscle cells contained randomly distributed, short and irregular myofibrils and individual myofilaments. The cytologic appearance of these muscle cells was similar to that of developing muscle cells. The pathogenesis of the myopathy in myotonic dystrophy may be related to myofibrillogenesis and its maintenance.

Humans↗
PubMed2005

Activation of cardiac and smooth muscle-specific genes in primary human cells after forced expression of human myocardin.

OBJECTIVE: Myocardin is a recently discovered transcriptional regulator of cardiac and smooth muscle development. Its ability to transactivate smooth muscle-specific genes has been firmly established in animal cells but its effect on heart muscle genes has been investigated less extensively and the consequences of ectopic myocardin expression in human cells are unknown. METHODS: In this study, primary human mesenchymal stem cells and foreskin fibroblasts were transduced with human adenovirus vectors expressing the longest splice variant of the human myocardin gene (hAd5/F50.CMV.myocL) or with control vectors. One week later, the expression of muscle-restricted genes in these cells was analyzed by reverse transcription-polymerase chain reactions and immunofluorescence microscopy. RESULTS: Forced expression of myocardin induced transcription of cardiac and smooth muscle genes in both cell types but did not lead to activation of skeletal muscle-specific genes. Double labeling experiments using monoclonal antibodies directed against striated (i.e. sarcomeric alpha-actin and sarcomeric alpha-actinin) and cardiac (i.e. natriuretic peptide precursor A) muscle-specific proteins together with a polyclonal antiserum specific for smooth muscle myosin heavy chain revealed that hAd5/F50.CMV.myocL-transduced cells co-express heart and smooth muscle-specific genes. CONCLUSIONS: These data indicate that the myocardin protein is a strong inducer of both smooth and cardiac muscle genes, but that additional factors are necessary to fully commit cells to either cardiac or smooth muscle cell fates.

Actinin↗
PubMed1997

Sport psychiatry in childhood and adolescence: an overview.

This review explores the importance and relevance of sport during childhood and adolescence, utilizing traditional stage theories of development. The literature supports the notion that sport is a necessary study as a health issue and a preventative tool in the field of psychiatry. Play and sport in childhood and adolescence enhance development physically, mentally, and socially. Participating in athletics encourages the development of leadership skills, self-esteem, muscle development and overall physical health. There is a lack of literature in the important area of sport psychiatry especially when considering beneficial, not deficit oriented youth athletic development. Child psychiatrists need to begin researching sport in order to develop a comprehensive understanding of how athletics can enhance the mental and physical health of youth.

Adolescent↗
PubMedDate not supplied

Pathway selection by growth cones of identified motoneurones in live zebra fish embryos.

How is the adult pattern of connections between motoneurones and the muscles that they innervate established during vertebrate development? Populations of motoneurones are thought to follow one of two patterns of development: (1) motor axons initially follow stereotyped pathways and project to appropriate regions of the developing muscle or (2) motor axons initially project to some regions that are incorrect, the inappropriate projections being eliminated subsequently. Here we observed individually identified motoneurones in live zebra fish embryos as they formed growth cones and as their growth cones navigated towards their targets. We report that from axogenesis, each motor axon followed a stereotyped pathway and projected only to the specific region of the muscle appropriate for its adult function. In addition, the peripheral arbor established by each motoneurone was restricted to a stereotyped region of its own segment and did not overlap with the peripheral arbor of the other motoneurones in that segment. We conclude that the highly stereotyped pattern of innervation seen in the adult is due to initial selection of the appropriate pathway, rather than elimination of incorrect projections.

Animals↗