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Carlsson, Lena
Publications (10 of 11) Show all publications
Thornell, L.-E., Carlsson, L., Eriksson, P.-O., Liu, J.-X., Österlund, C., Stål, P. & Pedrosa-Domellöf, F. (2015). Fibre typing of intrafusal fibres. Journal of Anatomy, 227(2), 136-156
Open this publication in new window or tab >>Fibre typing of intrafusal fibres
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2015 (English)In: Journal of Anatomy, ISSN 0021-8782, E-ISSN 1469-7580, Vol. 227, no 2, p. 136-156Article, review/survey (Refereed) Published
Abstract [en]

The first descriptions of muscle spindles with intrafusal fibres containing striated myofibrils and nervous elements were given approximately 150years ago. It took, however, another 100years to establish the presence of two types of intrafusal muscle fibres: nuclear bag and nuclear chain fibres. The present paper highlights primarily the contribution of Robert Banks in fibre typing of intrafusal fibres: the confirmation of the principle of two types of nuclear bag fibres in mammalian spindles and the variation in occurrence of a dense M-band along the fibres. Furthermore, this paper summarizes how studies from the Umea University group (Laboratory of Muscle Biology in the Department of Integrative Medical Biology) on fibre typing and the structure and composition of M-bands have contributed to the current understanding of muscle spindle complexity in adult humans as well as to muscle spindle development and effects of ageing. The variable molecular composition of the intrafusal sarcomeres with respect to myosin heavy chains and M-band proteins gives new perspectives on the role of the intrafusal myofibrils as stretch-activated sensors influencing tension/stiffness and signalling to nuclei.

Place, publisher, year, edition, pages
John Wiley & Sons, 2015
Keywords
cytoskeleton, M-band, M-protein, muscle spindle, myomesin, nuclear bag, nuclear chain, titin
National Category
Other Biological Topics
Identifiers
urn:nbn:se:umu:diva-106768 (URN)10.1111/joa.12338 (DOI)000357951900004 ()26179023 (PubMedID)
Available from: 2015-08-20 Created: 2015-08-07 Last updated: 2018-06-07Bibliographically approved
Yu, J.-G., Liu, J.-X., Carlsson, L., Thornell, L.-E. & Stål, P. S. (2013). Re-evaluation of sarcolemma injury and muscle swelling in human skeletal muscles after eccentric exercise. PLoS ONE, 8(4), Article ID e62056.
Open this publication in new window or tab >>Re-evaluation of sarcolemma injury and muscle swelling in human skeletal muscles after eccentric exercise
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2013 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 4, article id e62056Article in journal (Refereed) Published
Abstract [en]

The results regarding the effects of unaccustomed eccentric exercise on muscle tissue are often conflicting and the aetiology of delayed onset muscle soreness (DOMS) induced by eccentric exercise is still unclear. This study aimed to re-evaluate the paradigm of muscular alterations with regard to muscle sarcolemma integrity and fibre swelling in human muscles after voluntary eccentric exercise leading to DOMS. Ten young males performed eccentric exercise by downstairs running. Biopsies from the soleus muscle were obtained from 6 non-exercising controls, 4 exercised subjects within 1 hour and 6 exercised subjects at 2-3 days and 7-8 days after the exercise. Muscle fibre sarcolemma integrity, infiltration of inflammatory cells and changes in fibre size and fibre phenotype composition as well as capillary supply were examined with specific antibodies using enzyme histochemistry and immunohistochemistry. Although all exercised subjects experienced DOMS which peaked between 1.5 to 2.5 days post exercise, no significant sarcolemma injury or inflammation was detected in any post exercise group. The results do not support the prevailing hypothesis that eccentric exercise causes an initial sarcolemma injury which leads to subsequent inflammation after eccentric exercise. The fibre size was 24% larger at 7-8 days than at 2-3 days post exercise (p<0.05). In contrast, the value of capillary number per fibre area tended to decrease from 2-3 days to 7-8 days post exercise (lower in 5 of the 6 subjects at 7-8 days than at 2-3 days; p<0.05). Thus, the increased fibre size at 7-8 days post exercise was interpreted to reflect fibre swelling. Because the fibre swelling did not appear at the time that DOMS peaked (between 1.5 to 2.5 days post exercise), we concluded that fibre swelling in the soleus muscle is not directly associated with the symptom of DOMS.

National Category
Sport and Fitness Sciences
Identifiers
urn:nbn:se:umu:diva-68821 (URN)10.1371/journal.pone.0062056 (DOI)000317563300048 ()23614012 (PubMedID)
Available from: 2013-04-25 Created: 2013-04-25 Last updated: 2018-06-08Bibliographically approved
Carlsson, L., Yu, J.-G. & Thornell, L.-E. (2008). New aspects of obscurin in human striated muscles.. Histochemistry and Cell Biology, 130(1), 91-103
Open this publication in new window or tab >>New aspects of obscurin in human striated muscles.
2008 (English)In: Histochemistry and Cell Biology, ISSN 0948-6143, E-ISSN 1432-119X, Vol. 130, no 1, p. 91-103Article in journal (Refereed) Published
Abstract [en]

Obscurin is a giant protein (700-800 kDa) present in both skeletal muscles and myocardium. According to animal studies, obscurin interacts with myofibrillar Z-discs during early muscle development, but is translocalised to be predominantly associated with the M-bands in mature muscles. The proposed function for obscurin is in the assembly and organisation of myosin into regular A-bands during formation of new sarcomeres. In the present study, the precise localisation of obscurin in developing and mature normal human striated muscle is presented for the first time. We show that obscurin surrounded myofibrils at the M-band level in both developing and mature human skeletal and heart muscles, which is partly at variance with that observed in animals. At maturity, obscurin also formed links between the peripheral myofibrils and the sarcolemma, and was a distinct component of the neuromuscular junctions. Obscurin should therefore be regarded as an additional component of the extrasarcomeric cytoskeleton. To test this function of obscurin, biopsies from subjects with exercise-induced delayed onset muscle soreness (DOMS) were examined. In these subjects, myofibrillar alterations related to sarcomerogenesis are observed. Our immunohistochemical analysis revealed that obscurin was never lacking in myofibrillar alterations, but was either preserved at the M-band level or diffusely spread over the sarcomeres. As myosin was absent in such areas but later reincorporated in the newly formed sarcomeres, our results support that obscurin also might play an important role in the formation and maintenance of A-bands.

National Category
Sport and Fitness Sciences
Identifiers
urn:nbn:se:umu:diva-19318 (URN)10.1007/s00418-008-0413-z (DOI)18350308 (PubMedID)
Available from: 2009-03-05 Created: 2009-03-05 Last updated: 2018-06-09
Carlsson, L., Yu, J.-G., Moza, M., Carpén, O. & Thornell, L.-E. (2007). Myotilin: a prominent marker of myofibrillar remodelling. Neuromuscular Disorders, 17(1), 61-68
Open this publication in new window or tab >>Myotilin: a prominent marker of myofibrillar remodelling
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2007 (English)In: Neuromuscular Disorders, ISSN 0960-8966, E-ISSN 1873-2364, Vol. 17, no 1, p. 61-68Article in journal (Refereed) Published
Abstract [en]

Myofibrillar remodelling with insertion of sarcomeres is a typical feature of biopsies taken from persons suffering of exercise-induced delayed onset muscle soreness. Here we studied the presence of the sarcomeric protein myotilin in eccentric exercise related lesions. Myotilin is a component of sarcomeric Z-discs and it binds several other Z-disc proteins, i.e. alpha-actinin, filamin C, F-actin and FATZ. Myotilin has previously been shown to be present in nemaline rods and central cores and to be mutated in limb girdle muscular dystrophy 1A (LGMD1A) and in a subset of myofibrillar myopathies, indicating an important role in Z-disc maintenance. Our findings on non-diseased muscle affected by eccentric exercise give new information on how myotilin is associated to myofibrillar components upon remodelling. We show that myotilin was present in increased amount in lesions related to Z-disc streaming and events leading to insertion of new sarcomeres in pre-existing myofibrils and can therefore be used as a marker for myofibrillar remodelling. Interestingly, myotilin is preferentially associated with F-actin rather than with the core Z-disc protein alpha-actinin during these events. This suggests that myotilin has a key role in the dynamic molecular events mediating myofibrillar assembly in normal and diseased skeletal muscle.

Place, publisher, year, edition, pages
Elsevier, 2007
Keywords
eccentric exercise, DOMS, Z-disc streaming
National Category
Sport and Fitness Sciences Neurology
Identifiers
urn:nbn:se:umu:diva-12682 (URN)10.1016/j.nmd.2006.09.007 (DOI)000244575300009 ()17056257 (PubMedID)
Available from: 2008-01-11 Created: 2008-01-11 Last updated: 2018-06-09Bibliographically approved
Eriksson, A., Lindström, M., Carlsson, L. & Thornell, L.-E. (2006). Hypertrophic muscle fibers with fissures in power-lifters; fiber splitting or defect regeneration?. Histochemistry and Cell Biology, 126(4), 409-417
Open this publication in new window or tab >>Hypertrophic muscle fibers with fissures in power-lifters; fiber splitting or defect regeneration?
2006 (English)In: Histochemistry and Cell Biology, ISSN 0948-6143, E-ISSN 1432-119X, Vol. 126, no 4, p. 409-417Article in journal (Refereed) Published
Abstract [en]

Power-lifters have hypertrophic muscle fibers with fissures seen in cross-sections, called as fiber splitting.Whether this phenomenon is due to real splitting or defective regeneration has not been settled. To elucidate this matter,we have examined biopsies from the trapezius and vastus lateralis of power lifters (P group) and power lifters self-administrating anabolic steroids (PAS group). For this purpose, immunohistochemical staining of serial cross -sections was used. The PAS group had significantly more fibers with fissures than the P group in the vastus lateralis (1.2%+/-0.95% vs 0.35+/-0.34, P < 0.05) but not in the trapezius muscle (1.7% in both groups). Serial sections revealed that the fibers with fissures changed their profile profoundly over short distances. Some such fibers had a mature staining profile, whereas other fibers indicated recent degeneration and/or regeneration. Activation of satellite cells and formation of aberrant segments were also evident. We conclude that the so-called split fibers are due to defect regeneration. Some fibers with fissures are the results of old events of segmental muscle fiber damage, whereas the others reflect an ongoing process. The normal regenerative process is most likely disturbed in power-lifters by their continuous training with repeated high mechanical stress on the muscles.

Keywords
Adult, Anabolic Agents/administration & dosage, Humans, Hypertrophy, Immunohistochemistry, Male, Muscle Fibers/*pathology/*physiology, Muscle; Skeletal/drug effects/ultrastructure, Regeneration, Self Administration, Steroids/administration & dosage, Weight Lifting
Identifiers
urn:nbn:se:umu:diva-12683 (URN)10.1007/s00418-006-0176-3 (DOI)16625366 (PubMedID)
Available from: 2008-01-11 Created: 2008-01-11 Last updated: 2018-06-09Bibliographically approved
Yu, J.-G., Carlsson, L. & Thornell, L.-E. (2004). Evidence for myofibril remodeling as opposed to myofibril damage in human muscles with DOMS: an ultrastructural and immunoelectron microscopic study.. Histochemistry and Cell Biology, 121(3), 219-227
Open this publication in new window or tab >>Evidence for myofibril remodeling as opposed to myofibril damage in human muscles with DOMS: an ultrastructural and immunoelectron microscopic study.
2004 (English)In: Histochemistry and Cell Biology, ISSN 0948-6143, E-ISSN 1432-119X, Vol. 121, no 3, p. 219-227Article in journal (Refereed) Published
Abstract [en]

The myofibrillar and cytoskeletal alterations observed in delayed onset muscle soreness (DOMS) caused by eccentric exercise are generally considered to represent damage. By contrast our recent immunohistochemical studies suggested that the alterations reflect myofibrillar remodeling (Yu and Thornell 2002; Yu et al. 2003). In the present study the same human muscle biopsies were further analyzed with transmission electron microscopy and immunoelectron microscopy. We show that the ultrastructural hallmarks of DOMS, Z-disc streaming, Z-disc smearing, and Z-disc disruption were present in the biopsies and were significantly more frequent in biopsies taken 2-3 days and 7-8 days after exercise than in those from controls and 1 h after exercise. Four main types of changes were observed: amorphous widened Z-discs, amorphous sarcomeres, double Z-discs, and supernumerary sarcomeres. We confirm by immunoelectron microscopy that the main Z-disc protein alpha-actinin is not present in Z-disc alterations or in the links of electron-dense material between Z-discs in longitudinal register. These alterations were related to an increase of F-actin and desmin, where F-actin was present within the strands of amorphous material. Desmin, on the other hand, was seen in less dense regions of the alterations. Our results strongly support that the myofibrillar and cytoskeletal alterations, considered to be the hallmarks of DOMS, reflect an adaptive remodeling of the myofibrils.

Keywords
Actinin/metabolism, Actins/metabolism, Adaptation; Physiological, Adult, Desmin/metabolism, Exercise/*physiology, Humans, Immunohistochemistry, Male, Microscopy; Immunoelectron, Muscles/*metabolism/ultrastructure, Myofibrils/*metabolism/ultrastructure, Sarcomeres/*metabolism/ultrastructure
National Category
Sport and Fitness Sciences
Identifiers
urn:nbn:se:umu:diva-12675 (URN)10.1007/s00418-004-0625-9 (DOI)14991331 (PubMedID)
Available from: 2008-01-11 Created: 2008-01-11 Last updated: 2018-06-09
Agarkova, I., Schoenauer, R., Ehler, E., Carlsson, L., Carlsson, E., Thornell, L.-E. & Perriard, J.-C. (2004). The molecular composition of the sarcomeric M-band correlates with muscle fiber type. European Journal of Cell Biology, 83(5), 193-204
Open this publication in new window or tab >>The molecular composition of the sarcomeric M-band correlates with muscle fiber type
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2004 (English)In: European Journal of Cell Biology, ISSN 0171-9335, Vol. 83, no 5, p. 193-204Article in journal (Refereed) Published
Abstract [en]

The M-band is the transverse structure that cross-links the thick filaments in the center and provides a perfect alignment of the A-band in the activated sarcomere. The molecular composition of the M-bands in adult mouse skeletal muscle is fiber-type dependent. All M-bands in fast fibers contain M-protein while M-bands in slow fibers contain a significant proportion of the EH-myomesin isoform, previously detected only in embryonic heart muscle. This fiber-type specificity develops during the first postnatal weeks. However, the ratio between the amounts of myosin and of myomesin, taken as sum of both isoforms, remains nearly constant in all studied muscles. Ultrastructural analysis demonstrates that some of the soleus fibers show a diffuse appearance of the M-band, resembling the situation in the embryonic heart. A model is proposed to explain the functional consequence of differential M-band composition for the physiological and morphological properties of sarcomeres in different muscle types.

Keywords
Animals, Hindlimb/chemistry/metabolism, Mice, Microscopy; Electron, Muscle Fibers/*chemistry/metabolism, Muscle Fibers; Slow-Twitch/chemistry/metabolism, Muscle Proteins/chemistry/genetics/metabolism, Muscle; Skeletal/chemistry/metabolism/ultrastructure, Protein Isoforms/chemistry/genetics/metabolism, Sarcomeres/*chemistry/metabolism
National Category
Basic Medicine
Identifiers
urn:nbn:se:umu:diva-12687 (URN)15346809 (PubMedID)
Available from: 2007-11-30 Created: 2007-11-30 Last updated: 2018-06-09Bibliographically approved
Carlsson, L., Fischer, C., Sjöberg, G., Robson, R. M., Sejersen, T. & Thornell, L.-E. (2002). Cytoskeletal derangements in hereditary myopathy with a desmin L345P mutation. Acta Neuropathologica, 104(5), 493-504
Open this publication in new window or tab >>Cytoskeletal derangements in hereditary myopathy with a desmin L345P mutation
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2002 (English)In: Acta Neuropathologica, ISSN 0001-6322, E-ISSN 1432-0533, Vol. 104, no 5, p. 493-504Article in journal (Refereed) Published
Abstract [en]

Patients with abnormal accumulations of desmin have been described in myopathies with or without cardiac involvement. Desmin deposits were sometimes associated with abnormal aggregates of other cytoskeletal proteins. In the present study we present how the cytoskeletal organisation of desmin, nestin, synemin, paranemin, plectin and alphaB-crystallin is altered in skeletal muscles from a patient with a L345P mutation in the desmin gene. In general, accumulations of desmin together with synemin, nestin, plectin and alphaB-crystallin were present between myofibrils and beneath the sarcolemma. However, as the biopsy samples were very myopathic, large variability in fibre size and fibre maturation was seen, thus the myofibrillar content and the cytoskeletal organisation varied considerably. In cultured satellite cells from the patient, desmin aggregates were not observed in initial passages, but occurred over time in culture in the form of perinuclear, peripheral or cytoplasmic deposits. Nestin colocalised to the abnormal desmin deposits to a larger extent than did vimentin. alphaB-Crystallin was only present in cells with a disrupted desmin network. Plectin was altered in a subset of cells with a disrupted desmin network, whereas synemin and paranemin were not detected. We conclude that the L345P desmin mutation has a profound influence on the cytoskeletal organisation both in vivo and in vitro, which reflects the pathogenesis of the desmin myopathy.

Place, publisher, year, edition, pages
Springer, 2002
Keywords
Nestin, Synemin, Paranemin, Plectin, αB-Crystallin
National Category
Other Basic Medicine Health Sciences
Identifiers
urn:nbn:se:umu:diva-81909 (URN)10.1007/s00401-002-0583-z (DOI)12410397 (PubMedID)
Available from: 2013-10-23 Created: 2013-10-23 Last updated: 2018-06-08Bibliographically approved
Carlsson, L. & Thornell, L.-E. (2001). Desmin-related myopathies in mice and man. Acta Physiologica Scandinavica, 171(3), 341-8
Open this publication in new window or tab >>Desmin-related myopathies in mice and man
2001 (English)In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 171, no 3, p. 341-8Article in journal (Refereed) Published
Abstract [en]

Desmin, the main intermediate filament (IF) protein in skeletal and heart muscle cells, is of great importance as a part of the cytoskeleton. The IFs surround and interlink myofibrils, and connect the peripheral myofibrils with the sarcolemma. In myotendinous junctions and neuromuscular junctions of skeletal muscle fibres, desmin is enriched. In the heart, desmin is increased at intercalated discs, the attachment between cardiomyocytes, and it is the main component in Purkinje fibres of the conduction system. Desmin is the first muscle-specific protein to appear during myogenesis. Nevertheless, lack of desmin, as shown from experiments with desmin knockout (K/O) mice, does not influence myogenesis or myofibrillogenesis. However, the desmin knock-out mice postnatally develop a cardiomyopathy and a muscle dystrophy in highly used skeletal muscles. In other skeletal muscles the organization of myofibrils is remarkably unaffected. Thus, the main consequence of the lack of desmin is that the muscle fibres become more susceptible to damage. The loss of membrane integrity leads to a dystrophic process, with degeneration and fibrosis. In the heart cardiac failure develops, whereas in affected skeletal muscles regenerative attempts are seen. In humans, accumulations of desmin have been a hallmark for presumptive desmin myopathies. Recent investigations have shown that some families with such a myopathy have a defect in the gene coding for alphaB-crystallin, whereas others have mutations in the desmin gene. Typical features of these patients are cardiac affections and muscle weakness. Thus, mutations in the desmin gene is pathogenic for a distinct type of muscle disorder.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2001
Keywords
costameres, cytoskeleton, heart, intercalated discs, intermediate filaments, myotendinous junction, neuromuscular junction, skeletal muscle
National Category
Other Basic Medicine Physiology
Identifiers
urn:nbn:se:umu:diva-81912 (URN)10.1046/j.1365-201x.2001.00837.x (DOI)11412147 (PubMedID)
Available from: 2013-10-23 Created: 2013-10-23 Last updated: 2018-06-08Bibliographically approved
Carlsson, L. (2001). The muscle cytoskeleton of mice and men: Structural remodelling in desmin myopathies. (Doctoral dissertation). Umeå: Umeå universitet
Open this publication in new window or tab >>The muscle cytoskeleton of mice and men: Structural remodelling in desmin myopathies
2001 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The muscle fibre cytoskeleton of skeletal and heart muscle cells is composed mainly of intermediate filaments (IFs), that surround the myofibrils and connect the peripheral myofibrils with the sarcolemma and the nuclear membrane. Desmin is the first muscle specific IF protein to be produced in developing muscles and is the main IF protein in mature muscles. In skeletal muscle, desmin is particularly abundant at myotendinous and neuromuscular junctions. In the heart an increased amount of desmin is found at intercalated discs and in Purkinje fibres of the conduction system. Interactions between the IFs themselves, and between IFs and other structures such as Z-discs and the sarcolemma, are mediated by intermediate filament associated proteins (IFAPs). A transgenic mice model, which lacks the desmin gene have been developed to study the function of desmin. In these mice, morphological abnormalities are observed in both heart and skeletal muscles. Similar defects have been observed in human myopathies, caused by different mutations in the desmin gene. In the present thesis, skeletal and heart muscles of both wild type and desmin knock-out (K/O) mice have been investigated. Furthermore the cytoskeletal organisation in skeletal muscles from human controls and from a patient with desmin myopathy was examined.

In the desmin K/O mice, no morphological alterations were observed during embryogenesis. These mice postnatally developed a cardiomyopathy and a muscle dystrophy in highly used skeletal muscles. Ruptures of the sarcolemma appear to be the primary event leading to muscle degeneration and fibrosis both in cardiac and affected skeletal muscles. In the heart the muscle degeneration gave rise to calcifications, whereas in skeletal muscles regeneration of affected muscle was seen.

In mature wild type mice, the IF proteins synemin and paranemin, and the IFAP plectin were present together with desmin at the myofibrillar Z-discs, the sarcolemma, the neuromuscular junctions and the myotendinous junctions. Nestin was only found in these junctional regions. In desmin K/O mice, all four proteins were detected at neuromuscular and myotendinous junctions. The normal network of synemin and paranemin were not observed, whereas the distribution of plectin was preserved.

In normal human muscles, synemin, paranemin, plectin and αB-crystallin were colocalised with desmin in between the myofibrils, at the sarcolemma and at myotendinous and neuromuscular junctions. In the human desmin myopathy, the distribution of desmin varied considerably. A normal pattern was seen in some fibres areas, whereas other regions either contained large subsarcolemmal and intermyofibrillar accumulations of desmin or totally lacked desmin. Nestin, synemin, paranemin, plectin and αB-crystallin also exhibited an abnormal distribution. They were often aggregated in the areas that contained accumulations of desmin.

In cultured satellite cells from the patient, a normal network of desmin was present in early passages, whereas aggragates of desmin occurred upon further culturing. In the latter, also the nestin network was disrupted, whereas vimentin showed a normal pattern. αB-crystallin was only present in cells with a disrupted desmin network. Plectin was present in a subset of cells, irrespective of whether desmin was aggregated or showed a normal network.

From the present study it can be concluded that an intact desmin network is needed to maintain the integrity of muscle fibres. Desmin may be an important component in the assembly of proteins, which connect the extrasarcomeric cytoskeleton with the extracellular matrix.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2001. p. 45
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 754
Keywords
desmin, nestin, synemin, paranemin, plectin, αB-crystallin, skeletal muscle, heart muscle, myotendinous junction, motor endplate, costamere
National Category
Basic Medicine
Research subject
Human Anatomy
Identifiers
urn:nbn:se:umu:diva-83451 (URN)91-7305-122-5 (ISBN)
Public defence
2001-11-01, Stora föreläsningssalen, biologihuset, Umeå universitet, Umeå, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2014-03-26 Created: 2013-11-26 Last updated: 2018-06-08Bibliographically approved
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