Skip to main content
Log in

Muscle damage and repair in voluntarily running mice: strain and muscle differences

  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Summary

Soleus, extensor digitorum longus and tibialis anterior muscles of mice voluntarily running in wheels for periods of 5 to 120 days were studied in spaced serial and serial cross-sections. Shortly after the onset of running and during the next 2 weeks, degeneration, necrosis, phagocytosis and regeneration of muscle fibers, satellite cell proliferation and cellular infiltration were found in soleus muscles of mice from all strains investigated (CBA/J, NMRI, C57b, NIH, SWS and Balb/c). Tibialis anterior but not extensor digitorum longus muscles were also damaged. Predominantly high-oxidative fibers were affected (both slow-oxidative and fast oxidative glycolytic in soleus, fast-oxidative glycolytic in tibialis anterior). Denervated soleus muscles that had been passively stretched during running were not damaged. Evidence was found that, during the early period of running, split fibers form by myogenesis within (regeneration) or outside (satellite cell proliferation) necrotic muscle fiber segments. Split fibers persisted in solei of long-term (2 to 3 months) exercised CBA/J but not NMRI mice. In 6 out of 20 solei of CBA/J runners exercised for 2 months or longer, fiber-type grouping was observed in the areas where extensive damage usually occurred in the early periods. The results show that different muscles are damaged and repaired to varying degrees and that marked interstrain and inter-individual differences are present. It appears that acute muscle injury occurring upon onset of voluntary running is a usual event in the adaptation of muscles to altered use.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Armstrong RB, Ogilvie RW, Schwane JA (1983) Eccentric exerciseinduced injury to rat skeletal muscle. J Appl Physiol 54:80–93

    Google Scholar 

  • Atherton GW, James NT, Mahon M (1981) Studies on mucle fibre splitting in skeletal muscle. Experientia 37:308–310

    Google Scholar 

  • Baldwin KM, Klinkerfuss GH, Terjung RL, Mole PA, Holloszy JO (1972) Respiratory capacity of white, red, and intermediate muscle: adaptive response to exercise. Am J Physiol 222:373–378

    Google Scholar 

  • Barka T, Anderson PJ (1963) Histochemistry: theory, practice and bibliography. Harper & Row, New York

    Google Scholar 

  • Bartsch RC, McConncll EE, Imes GD, Schmidt JM (1977) A review of exertional rhabdomyolysis in wild and domestic animals and men. Vet Pathol 14:314–324

    Google Scholar 

  • Blinzinger K, Kreutzberg G (1968) Displacement of synaptic terminals from regenerating motoneurons by microglial cells. Z Zellforsch 85:145–157

    Google Scholar 

  • Bosanquet FD, Daniel PM, Parry HB (1973) Myopathy, the pathological changes in intrinsic diseases of muscle. In: Bourne GH (ed) The structure and function of muscle. Vol IV. Pharmacology and disease. Academic Press, New York London, pp 359–431

    Google Scholar 

  • Bourke DL, Ontell M (1984) Branched myofibers in long-term whole muscle transplants: a quantitative study. Anal Rec 209:281–288

    Google Scholar 

  • Brodal P, Ingjer F, Hcrmanscn L (1977) Capillary supply of skeletal muscle fibers in untrained and endurance-trained men. Am J Physiol 232(6):H705-H712

    Google Scholar 

  • Bronson FH (1984) The adaptability of the house mouse. Sci Am 250:90–97

    Google Scholar 

  • Browman LG (1943) The effect of controlled temperatures upon the spontaneous activity rhythms of the albino rat. J Exp Zool 94:477–489

    Google Scholar 

  • Burstone MS (1962) Enzyme histochemistry and its application in the study of neoplasms. Academic Press, New York

    Google Scholar 

  • Butler J, Cosmos E (1981) Enzymic markers to identify musclenerve formation during embryogenesis: modified myosin ATPase and silver-cholinesterase histochemical reactions. Exp Neurol 73:831–836

    Google Scholar 

  • Carpenter S, Karpati G (1984) Pathology of skeletal muscle. Churchill Livingstone, New York Edinburgh London Melbourne

    Google Scholar 

  • Carraro U, Morale D, Mussini I, Lucke S, Cantini M, Betto R, Catani C, Libera LD, Betto DD, Noventa D (1985) Chronic denervation of rat hemidiaphragm: maintenance of fiber heterogeneity with associated increasing uniformity of myosin isoform. J Cell Biol 100:161–174

    Article  CAS  PubMed  Google Scholar 

  • Chou SM, Nonaka I (1977) Satellite cells and muscle regeneration in diseased human skeletal muscles. J Neurol Sci 34:131–145

    Google Scholar 

  • Dudley GA, Abraham WM, Terjung RL (1982) Influence of exercise intensity and duration on biochemical adaptations in skeletal muscle. J Appl Physiol 53:844–850

    Google Scholar 

  • Edgerton VR (1970) Morphology and histochemistry of the soleus muscle from normal and exercised rats. Am J Anat 127:81–88

    Google Scholar 

  • Edgerton VR (1978) Mammalian muscle fiber types and their adaptability. Am Zool 18:113–125

    Google Scholar 

  • Elder GCB, Vassallo F (1986) Histochemical and contractile properties of soleus muscle trained during development. Pflügers Arch 407:116–169

    Google Scholar 

  • Geller SA (1973) Extreme exertion rhabdomyolysis. A histopathologic study of 31 cases. Human Pathol 4:241–250

    Google Scholar 

  • Gollnick PD, King DW (1969) Effect of exercise and training on mitochondria of rat skeletal muscle. Am J Physiol 216:1502–1509

    Google Scholar 

  • Gollnick PD, Armstrong RB, Saubert IV CW, Piehl K, Saltin B (1972) Enzyme activity and fiber composition in skeletal muscle of untrained and trained men. J Appl Physiol 33:312–319

    Google Scholar 

  • Gonyea WJ, Ericson GC, Bonde-Petersen G (1977) Skeletal muscle fiber splitting induced by weight-lifting exercise in cats. Acta Physiol Scand 99:105–109

    Google Scholar 

  • Green HJ, Reichmann H, Pette D (1983) Fibre type specific transformations in the enzyme activity pattern of rat vastus lateralis muscle by prolonged endurance training. Pflügers Arch 399:216–222

    Google Scholar 

  • Green HJ, Klug GA, Reichmann H, Seedorf U, Wiehrer W, Pette D (1984) Exercise-induced fibre type transitions with regard to myosin, parvalbumin, and sarcoplasmic reticulum in muscles of the rat. Pflügers Arch 400:432–438

    Google Scholar 

  • Greenberg J, Arneson L (1967) Exertional rhabdomyolysis with myoglobinuria in a large group of military trainees. Neurology 17:216–222

    Google Scholar 

  • Hall-Craggs ECB (1970) The longitudinal divison of fibres in overloaded rat skeletal muscle. J Anat 107:459–470

    Google Scholar 

  • Hall-Craggs ECB (1972) The significance of longitudinal fibre division in skeletal muscle. J Neurol Sci 15:27–33

    Google Scholar 

  • Hall-Crags ECB, Lawrence CA (1970) Longitudinal fibre division in skeletal muscle: a lightand electronmicroscopic study. Z Zellforsch 109:481–494

    Google Scholar 

  • Hamilton RW, Gardner LB, Penn AS, Goldberg M (1972) Acute tubular necrosis caused by exercise-induced myoglobinuria. Ann Int Med 77:77–82

    Google Scholar 

  • Hecht A, Schumann H-J, Kunde D (1975) Histologische und enzymhistochemische Befunde am Skelettmuskel der untrainierten Ratte nach intensiver physischer Belastung. Med Sport 15:270–274

    Google Scholar 

  • Highman B, Altland PD (1963) Effects of exercise and training on serum enzyme and tissue changes in rats. Am J Physiol 205:162–166

    Google Scholar 

  • Hikida RS, Staron RS, Hagerman FC, Sherman WM, Costill DL (1983) Muscle fiber necrosis associated with human marathon runners. J Neurol Sci 59:185–203

    Google Scholar 

  • Howald H, Hoppeler H, Claasen H. Mathieu O, Straub R (1985) Influence of endurance training on the ultrastructural composition of the different muscle fiber types in humans. Pflügers Arch 403:369–376

    Google Scholar 

  • Howenstine JA (1960) Exertion-induced myoglobinuria and hemoglobinuria. JAMA 173:490–499

    Google Scholar 

  • Ingjer F (1979) Effects of endurance training on muscle fibre ATP-ase activity, capillary supply and mitochondrial content in man. J Physiol 294:419–432

    Google Scholar 

  • James NT (1973) Compensatory hypertrophy in the extensor digitorum longus muscle of the rat. J Anat 116:57–65

    Google Scholar 

  • Jones DA, Newham DJ, Round JM, Tolfree SEJ (1986) Experiental human muscle damage: morphological changes in relation to other indices of damage. J Physiol 375:435–448

    Google Scholar 

  • Karnovsky MJ, Roots LA (1964) A ‘direct-coloring’ thio-choline method for cholinesterases. J Histochem Cytochem 12:219–221

    Google Scholar 

  • Karpati G, Carpenter S, Melmed C, Eisen AA (1974) Experimental ischemic myopathy. J Neurol Sci 23:129–161

    Google Scholar 

  • Knochel JP (1982) Rhabdomyolysis and myoglobinuria. Ann Rev Med 33:435–443

    Google Scholar 

  • Kugelberg E (1976) Adaptive transformation of rat soleus motor units during growth. J Neurol Sci 27:269–289

    Google Scholar 

  • Kuipers H, Drukker J, Frederik PM, Geurten P, v Kranenburg G (1983) Muscle degeneration after exercise in rats. Int J Sport Med 4:45–51

    Google Scholar 

  • Lojda Z, Gossrau R, Schiebler TH (1976) Enzymhistochemische Methoden. Springer, Berlin Heidelberg New York

    Google Scholar 

  • Maier A, Gambke B, Pette D (1986) Degeneration-regeneration as a mechanism contributing to the fast to slow conversion of chronically stimulated fast-twitch rabbit muscle. Cell Tissue Res 244:635–643

    Google Scholar 

  • Mendell L (1984) Modifiability of spinal synapses. Physiol Rev 64:260–324

    Google Scholar 

  • Miledi R, Slater CR (1969) Electron-microscopic structure of denervated skeletal muscle. Proc R Soc Lond [Biol] 174:253–269

    Google Scholar 

  • Nachlas MM, Tsou KC, DeSouza E, Cheng CS, Seligman AM (1957) Cytochemical demonstration of succinic dehydrogenase by the use of a new p-nitrophenyl substituted ditetrazole. J Histochem Cytochem 5:420–436

    Google Scholar 

  • Newham DJ, Jones DA, Edwards RHT (1983) Large delayed plasma creatine kinase changes after stepping exercise. Muscle Nerve 6:380–385

    Google Scholar 

  • O'Donnell TF (1971) Medical problems of recruit training. US Navy Med 58:28–34

    Google Scholar 

  • Ono I (1953) Studies on myoglobinuria. Tohoku J Exp Med 57:273–281

    Google Scholar 

  • Ontell M, Feng KC (1981) The three-dimensional cytoarchitecture and pattern of motor innervation of branched striated myotubes. Anat Res 200:1–31

    Google Scholar 

  • Ontell M, Hughes D, Bourke D (1982) Secondary myogenesis of normal muscle produces abnormal myotubes. Anat Rec 204:199–207

    Google Scholar 

  • Pette D, Vrbová G (1985) Neural control of phenotypic expression in mammalian muscle fibers. Muscle Nerve 8:676–689

    Google Scholar 

  • Salminen A, Vihko V (1980) Acid proteolytic capacity in mouse cardiac and skeletal muscles after prolonged submaximal exercise. Pflüges Arch 389:17–20

    Google Scholar 

  • Saltin B, Henriksson J, Nygaard E, Andersen P, Jansson E (1977) Fiber types and metabolic potentials of skeletal muscles in sedentary man and endurance runners. Ann NY Acad Sci 301:3–29

    Google Scholar 

  • Schiaffino S, Pierobon Bormioli S, Aloisi M (1979) Fiber branching and formation of new fibers during compensatory muscle hypertrophy. In: Mauro A (ed) Muscle regeneration. Raven Press, New York, pp 177–188

    Google Scholar 

  • Schmalbruch H (1976) Muscle fibre splitting and regeneration in diseased human muscles. Neuropathol Appl Neurobiol 2:3–19

    Google Scholar 

  • Schmalbruch H (1984) Regenerated muscle fibers in Duchenne muscular dystrophy: a serial section study. Neurology 34:60–65

    Google Scholar 

  • Schmid R, Mahler R (1959) Chronic progressive myopathy with myoglobinuria: demonstration of a glycogenolytic defect in the muscle. J Clin Invest 38:2044–2058

    Google Scholar 

  • Schön FA, Hollmann W, Liesen H, Waterloh E (1980) Electronenmikroskopische Befunde am Musculus vastus lateralis von Untrainierten und Marathonläufern sowie ihre Beziehung zur relativen maximalen Sauerstoffaufnahme und Laktatproduktion. Deutsche Z Sportmed 31:343–348

    Google Scholar 

  • Schumann HJ (1967) Experimentelle Skelettmuskelnekrosen nach Laufzwang. Morph J 111:107–111

    Google Scholar 

  • Schwartz MS, Sargeant M, Swash M (1976) Longitudinal fiber splitting in neurogenic muscular disorders: its relation to the pathogenesis of “myopathic” change. Brain 99:67–636

    Google Scholar 

  • Sher I, Cardasis C (1976) Skeletal muscle fiber types in the adult mouse. Acta Neurol Scand 54:45–56

    Google Scholar 

  • Silberman M, Finkelbrand S, Weiss A, Gershon D, Reznick A (1983) Morphometric analysis of aging skeletal muscle following endurance training. Muscle Nerve 6:136–142

    Google Scholar 

  • Sjöström M, Fridén J, Ekblom B (1982) Fine structural details of human muscle fibers after fiber type specific glycogen depletion. Histochemistry 76:426–438

    Google Scholar 

  • Smith RF (1968) Exertional rhabdomyolysis in naval officer candidates. Arch Int Med 121:313–319

    Google Scholar 

  • Sola OM, Christensen DL, Martin AW (1973) Hypertrophy and hyperplasia of adult chicken anterior latissimus dorsi muscles following stretch with and without denervation. Exp Neurol 41:76–100

    Article  CAS  PubMed  Google Scholar 

  • Swash M, Schwartz MS, Sargeant MK (1978) Pathogenesis of longitudinal splitting of muscle fibres in neurogenic disorders and in polymyositis. Neuropathol Appl Neurobiol 4:99–115

    Google Scholar 

  • Van Linge B (1962) The response of muscle to strenuous exercise. An experimental study in the rat. J Bone Joint Surg [Br] 44B:711–721

    Google Scholar 

  • Vaughan HS, Goldspink G (1979) Fibre number and fibre size in a surgically overloaded muscle. J Anat 129:293–303

    Google Scholar 

  • Vihko V, Rantamäki J, Salminen A (1978a) Exhaustive physical exercise and acid hydrolase activity in mouse skeletal muscle. Histochemistry 57:237–249

    Google Scholar 

  • Vihko V, Salminen A, Rantamäki J (1978b) Acid hydrolase activity in red and white skeletal muscle of mice during a two-week period following exhausting exercise. Pflügers Arch 378:99–106

    Google Scholar 

  • Vihko V, Salminen A, Rantamäki J (1979) Exhaustive exercise, endurance training, and acid hydrolase activity in skeletal muscle. J Appl Physiol 47:43–50

    Google Scholar 

  • Wernig A, Herrera AA (1986) Sprouting and remodelling at the nerve-muscle junction. Progr Neurobiol 27:251–291

    Google Scholar 

  • Wernig A, Irintchev A (1986) Strain and muscle specific response to voluntary exercise in mice. Neurosci Lett 26:S175

    Google Scholar 

  • Wernig A, Irintchev A, Schuhmacher H, Badke A (1987) Effects of prolonged voluntary running on normal and denervated leg muscles in different strains of mice. (In preparation)

  • Yellin H (1974) Changes in fiber types of the hypertrophying denervated hemidiaphragm. Exp Neurol 42:412–428

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Irintchev, A., Wernig, A. Muscle damage and repair in voluntarily running mice: strain and muscle differences. Cell Tissue Res. 249, 509–521 (1987). https://doi.org/10.1007/BF00217322

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00217322

Key words

Navigation