umu.sePublications
Change search
Refine search result
1234567 101 - 150 of 1290
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 101.
    Birznieks, Ingvars
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Jenmalm, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Goodwin, Antony W
    University of Melbourne, Victoria.
    Johansson, Roland S
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Encoding of direction of fingertip forces by human tactile afferents2001In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 21, no 20, p. 8222-8237Article in journal (Refereed)
    Abstract [en]

    In most manipulations, we use our fingertips to apply time-varying forces to the target object in controlled directions. Here we used microneurography to assess how single tactile afferents encode the direction of fingertip forces at magnitudes, rates, and directions comparable to those arising in everyday manipulations. Using a flat stimulus surface, we applied forces to a standard site on the fingertip while recording impulse activity in 196 tactile afferents with receptive fields distributed over the entire terminal phalanx. Forces were applied in one of five directions: normal force and forces at a 20 degrees angle from the normal in the radial, distal, ulnar, or proximal directions. Nearly all afferents responded, and the responses in most slowly adapting (SA)-I, SA-II, and fast adapting (FA)-I afferents were broadly tuned to a preferred direction of force. Among afferents of each type, the preferred directions were distributed in all angular directions with reference to the stimulation site, but not uniformly. The SA-I population was biased for tangential force components in the distal direction, the SA-II population was biased in the proximal direction, and the FA-I population was biased in the proximal and radial directions. Anisotropic mechanical properties of the fingertip and the spatial relationship between the receptive field center of the afferent and the stimulus site appeared to influence the preferred direction in a manner dependent on afferent type. We conclude that tactile afferents from the whole terminal phalanx potentially contribute to the encoding of direction of fingertip forces similar to those that occur when subjects manipulate objects under natural conditions.

  • 102.
    Birznieks, Ingvars
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Johansson, Roland S
    Response onset latencies in populations of human tactile afferents reflect direction of fingertip forces and object shapeManuscript (Other academic)
  • 103.
    Birznieks, Ingvars
    et al.
    Prince of Wales Medical Research Institute, Sydney, New South Wales 2031, Australia.
    Macefield, Vaughan G
    Prince of Wales Medical Research Institute, Sydney, New South Wales 2031, Australia.
    Westling, Göran
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Johansson, Roland S
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Slowly adapting mechanoreceptors in the borders of the human fingernail encode fingertip forces2009In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 29, no 29, p. 9370-9379Article in journal (Refereed)
    Abstract [en]

    There are clusters of slowly adapting (SA) mechanoreceptors in the skin folds bordering the nail. These "SA-IInail" afferents, which constitute nearly one fifth of the tactile afferents innervating the fingertip, possess the general discharge characteristics of slowly adapting type II (SA-II) tactile afferents located elsewhere in the glabrous skin of the human hand. Little is known about the signals in the SA-IInail afferents when the fingertips interact with objects. Here we show that SA-IInail afferents reliably respond to fingertip forces comparable to those arising in everyday manipulations. Using a flat stimulus surface, we applied forces to the finger pad while recording impulse activity in 17 SA-IInail afferents. Ramp-and-hold forces (amplitude 4 N, rate 10 N/s) were applied normal to the skin, and at 10, 20, or 30 degrees from the normal in eight radial directions with reference to the primary site of contact (25 force directions in total). All afferents responded to the force stimuli, and the responsiveness of all but one afferents was broadly tuned to a preferred direction of force. The preferred directions among afferents were distributed all around the angular space, suggesting that the population of SA-IInail afferents could encode force direction. We conclude that signals in the population of SA-IInail afferents terminating in the nail walls contain vectorial information about fingertip forces. The particular tactile features of contacted surfaces would less influence force-related signals in SA-IInail afferents than force-related signals present in afferents terminating in the volar skin areas that directly contact objects.

  • 104. Bitaraf, Nazanin
    et al.
    Ahmed, Ahmed
    Druzin, Michael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Ramser, Kerstin
    Development of a multifunctional microfluidic system for studies of nerve cell activity during hypoxic and anoxic conditions2009In: International Federation for Medical and Biological Engineering Proceedings; 25, 2009, p. 176-179Conference paper (Refereed)
    Abstract [en]

     

    Abstract

    —Hemoproteins usually supply cells and tissue

     with oxygen. A new hemoprotein mainly present in nerve cells called Neuroglobin was recently discovered. Enhanced expression of the protein has been shown to reduce hypoxic neural injury but the mechanism behind this function remains unknown. Methods enabling investigation of the protein in single functional neurons need to be developed. Here, we have studied how the electrical signaling capacity of a neuron was affected by hypoxic environments. Preliminary results show a trend of higher noise-level when a neuron is exposed to hypoxic compared to normoxic surroundings, which implies increased ion-channel activity. The setup used today shows shortages such as reduced control over the oxygen content due to leakage. Therefore, a gas-tight, multifunctional microfluidic system is under development which enables us to study influences of Neuroglobin concentrations on neuronal activity during hypoxia and anoxia. For electrophysiological recordings a patch-clamp micro pipette will be molded into the walls of the microfluidic system. A single biological cell is steered towards the pipette and attached there by means of optical tweezers. The Neuroglobin oxygen binding state will be studied using optical spectroscopy and the neuron environment will be manipulated by applying flows of varying oxygen content through the microfluidic system. This system will constitute a powerful tool in the investigation of the Neuroglobin mechanism of action. 

  • 105.
    Bjur, Dennis
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Sports Medicine. Umeå University, Faculty of Medicine, Integrative Medical Biology, Anatomy.
    The human Achilles tendon: innervation and intratendinous production of nerve signal substances - of importance in understanding the processes of Achilles tendinosis2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Tendinopathies are painful tendon conditions of presumably multifactorial genesis. In tendinosis, as in Achilles tendinosis, there is apart from pain also morphological changes which are described as degenerative with no signs of inflammation. The exact mechanisms behind these conditions are still, to a large extent, unknown. Pain, being the foremost impairing symptom, leads us to the hypothesis that nerves are deeply involved in the symptoms and processes of Achilles tendinosis. Locally produced nerve signal substances may also be involved in the processes. Knowledge of the innervation patterns within the tendon and knowledge on a possible local nerve signal substance production are therefore of utmost importance. There is a lack of information on these aspects.

    The specific aims of this thesis were 1) to investigate the innervation patterns regarding general, sensory, cholinergic and sympathetic innervations, and 2) to examine for the possible occurrence of a production of nerve signal substances and a presence of receptors related to these in the tendon cells, the tenocytes. Painfree normal and tendinosis Achilles tendons were examined.

    Immunohistochemistry, using antibodies against the general nerve marker PGP9.5, the synthesizing enzymes for acetylcholine (choline acetyltransferase; ChAT), and catecholamines (tyrosine hydroxylase; TH), the vesicular acetylcholine transporter (VAChT), neuropeptide Y (NPY), substance P and calcitonin gene-related peptide, was applied. Immunohistochemistry was also used for the delineation of muscarinic (M2R), adrenergic (α1-AR) and NPY-ergic (Y1 and Y2) receptors. To detect mRNA for TH and ChAT, in situ hybridization was used.

    In normal Achilles tendons, as well as in the tendinosis tendons, there was a very scanty innervation within the tendon tissue proper, the main general, sensory and sympathetic innervations being found in the paratendinous loose connective tissue. Interestingly, the tenocytes showed immunoreactions for ChAT, VAChT, TH, M2R, α1-AR and Y1R. The reactions were clearly more observable in tendons of tendinosis patients than in those of controls. The tenocytes of tendinosis patients also displayed mRNA reactions for ChAT and TH. Nevertheless, all tenocytes in the tendinosis specimens did not show these reactions. Immunoreactions for α1-AR, M2R and Y1R were also seen for blood vessel walls.

    The present thesis shows that there is a very limited innervation within tendon tissue proper, whilst there is a substantial innervation in the paratendinous loose connective tissue. It also gives evidence for an occurrence of production of catecholamines and acetylcholine in tenocytes, especially for tendinosis tendons. Furthermore, that ACh, catecholamines and NPY can have effects on these, as well as on blood vessels, via the receptors observed.

    The observations suggest that Achilles tendon tissue, whilst containing a very scarce innervation, exhibits autocrine/paracrine cholinergic/catecholaminergic/NPY-ergic effects that are upregulated in tendinosis. These findings are of great importance as the results of such effects may mimic processes that are known to occur in tendinosis. That includes effects related to proliferation and angiogenesis, and blood vessel and collagen regulating effects.

    In conclusion, within the Achilles tendon there is a very scarce innervation, whilst there appears to be a marked local production of nerve signal substances in Achilles tendinosis, namely in the tenocytes, the cells also harbouring receptors for these substances. The observations give a new insight into how the tendon tissue of the Achilles tendon is influenced by signal substances and may give options for new treatments of Achilles tendinosis.

  • 106.
    Bjur, Dennis
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Alfredson, Håkan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Presence of the neuropeptide Y 1 receptor in tenocytes and blood vessel walls in the human Achilles tendon2009In: British Journal of Sports Medicine, ISSN 0306-3674, E-ISSN 1473-0480, Vol. 43, no 13, p. 1136-1142Article in journal (Refereed)
    Abstract [en]

    Background: There are still questions concerning the mechanisms of development of chronic pain and impaired function of tendons (tendinosis). Aspects that are known to occur are cell proliferation, angiogenesis and altered blood flow regulation. Neuropeptide NPY (NPY) is widely distributed in the body and has powerful effects in relation to these processes. NPY has its effects via the G-protein-coupled Y receptors. There is no information concerning the presence or absence of NPY receptors in Achilles tendons or other tendons.

    Objective: To clarify the expression patterns of the NPY receptors Y1 and Y2 in normal and tendinosis Achilles tendons of man.

    Methods: Immunohistochemical methods were used. Examination on NPY was carried out in parallel.

    Results: The tenocytes showed strong immunoreactions for the Y1 receptor. The immunoreactions were more intense in the tenocytes of the tendinosis tendons than in those of the non-tendinosis tendons. The rounded/oval tenocytes typically seen in tendinosis tendons exhibited marked Y1 receptor reactions on their exterior. Pronounced Y1 reactions were seen in the smooth muscle of the arterioles of both tendinosis and non-tendinosis tendons. No reactions for the Y2 receptor were noted. NPY was detected in nerve fascicles and in the perivascular innervation.

    Conclusions: The present study shows that there is a morphologic correlate for the occurrence of pronounced NPY effects via the Y1 receptor in both tenocytes, this especially being a fact for tendinosis tendons, and blood vessel walls in the Achilles tendon. The findings are of particular interest as NPY is known to have proliferative, angiogenic and blood vessel regulating effects. The effects of targeting the Y1 receptor in tendinosis is an interesting task to be further evaluated.

  • 107.
    Bjur, Dennis
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Alfredson, Håkan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    The innervation pattern of the human Achilles tendon: studies of the normal and tendinosis tendon with markers for general and sensory innervation2005In: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 320, no 1, p. 201-206Article in journal (Refereed)
    Abstract [en]

    Pain-free normal Achilles tendons and chronic painful Achilles tendons were examined by the use of antibodies against a general nerve marker (protein gene-product 9.5, PGP9.5), sensory markers (substance P, SP; calcitonin gene-related peptide, CGRP), and immunohistochemistry. In the normal tendons, immunoreactions against PGP9.5 and against SP/CGRP were encountered in the paratendinous loose connective tissue, being confined to nerve fascicles and to nerve fibers located in the vicinity of blood vessels. To some extent, these immunoreactions also occurred in the tendon tissue proper. Immunoreaction against PGP9.5 and against SP/CGRP was also observed in the tendinosis samples and included immunoreactive nerve fibers that were intimately associated with small blood vessels. In conclusion, Mechanoreceptors (sensory corpuscles) were occasionally observed, nerve-related components are present in association with blood vessels in both the normal and the tendinosis tendon.

  • 108.
    Bjur, Dennis
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Danielson, Patrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Alfredson, Håkan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Immunohistochemical and in situ hybridization observations favor a local catecholamine production in the human Achilles tendon2008In: Histology and Histopathology, ISSN 0213-3911, E-ISSN 1699-5848, Vol. 23, no 2, p. 197-208Article in journal (Refereed)
    Abstract [en]

    Results of recent studies using immunohistochemistry show evidence of an occurrence of catecholamine production in the cells (tenocytes) of patellar tendons exhibiting tendinopathy (tendinosis). In the present study, antibodies against the catecholamine-synthesizing enzyme tyrosine hydroxylase (TH) and alpha1-adrenoreceptors were applied to sections of specimens of normal and tendinosis Achilles tendons. In situ hybridization using a probe detecting human TH mRNA was also utilized. It was found that sympathetic innervation was very scarce. On the other hand, there were distinct alpha1-adrenoreceptor immunoreactions in blood vessel walls. Interestingly, tenocytes, particularly from tendinosis samples in which the tenocytes showed an abnormal shape (not the typical slender appearance), displayed TH immunoreactions and reactions for TH mRNA. Of further interest was the finding of alpha1-adrenoreceptor immunoreactions in tenocytes. The observations show not only evidence of local catecholamine production at the protein level, which was the case in recent studies for the patellar tendon, but also at the mRNA level. The observations suggest that the tenocytes, especially those with disfigured appearances in tendinosis, can produce catecholamines and also that they can respond to sympathetic transmitters. This is of interest as adrenergic stimulation in other parts of the body is known to induce degenerative/apoptotic and proliferative events, features which are seen in Achilles tendinosis. These observations are completely new findings concerning the human Achilles tendon. It is likely that locally produced catecholamines and the occurrence of autocrine/paracrine effects of these substances are of great relevance during the process of tendinosis.

  • 109.
    Bjur, Dennis
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Danielson, Patrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Alfredson, Håkan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Observations in favor of a presence of local catecholamine production in the human Achilles tendon - of importance when understanding potential adrenergic effects in Achilles tendinosis.2006Conference paper (Refereed)
    Abstract [en]

    The mid-portion of the Achilles tendon is a frequently injured and pathologically affected tendon region. Achilles tendinosis presents with chronic tendon pain and impaired function, and most often occurs in the mid-portion of the tendon. Nerve-related effects are likely to be of great significance in the pathogenesis of this condition, and information on innervation patterns is therefore of importance. However, the available information on these aspects is limited for the human Achilles tendon. Via staining for a general nerve marker it has previously been shown that there is a presence of innervation in the loose paratendinous connective tissue and to some extent also within the tendon tissue proper. This innervation has been found to partly conform to sensory innervation. There is no information at all on the patterns of sympathetic innervation in the human Achilles tendon. This is a drawback as it is crucial to know the basis for adrenergic effects on blood vessel regulation in tendinosis and as efferent sympathetic nerve activities may be related to pain symptoms. In the present study, therefore, specimens of tendon tissue from the human Achilles tendon of both tendinosis patients and normal controls were immunohistochemically examined concerning expression of the rate limiting enzyme in catecholamine production, tyrosine hydroxylase (TH), and of neuropeptide Y (NPY). In normal tendons, TH- and NPY-immunoreactive nerve fibers were occasionally detected in nerve fascicles and in arterial walls in the paratendinous tissue, but were not detected with certainty within the tendon tissue proper. In the specimens of tendinosis affected tendons, TH-and NPY-immunoreactive nerve fibers were almost non-existent. Surprisingly, however, TH-immunoreactions could be seen in the tendon cells (tenocytes) themselves. Sections were also processed for demonstration of α1-, α2a-, and β1- adrenoreceptors. It was hereby seen that there were immunoreactions for adrenergic receptors in the walls of some of the blood vessels, as well as in some of the tenocytes. The observations show that there is a limited sympathetic innervation at the level of the paratendinous tissue and in principle a non-existent such innervation within the tendon tissue proper. On the other hand, as evidenced by findings of TH-immunoreaction in tenocytes, it appears as if there is a local production of catecholamines within the tendon tissue proper itself. Thus, the tenocytes might be an important source of mediators that bind to the adrenergic receptors in the tissue. The observations of adrenergic receptors on tenocytes are furthermore of interest as adrenergic stimulation in other situations can lead to degenerative/apoptotic events and an affection on cell growth. These facts are thus highly interesting when trying to understand how such events can occur in Achilles tendinosis. Similarly, cartilage and menisci have in recent studies been found to harbor cells that express adrenergic receptors, but nevertheless to be very scarcely equipped with nerves. Although there is a very limited sympathetic innervation in the Achilles tendon, our observations show that there is a morphologic correlate for the occurrence of adrenergic actions in the tendon, via effects of locally produced catecholamines.

  • 110.
    Bjur, Dennis
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Danielson, Patrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Alfredson, Håkan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Presence of a non-neuronal cholinergic system and occurrence of up- and down-regulation in expression of M2 muscarinic acetylcholine receptors: new aspects of importance regarding Achilles tendon tendinosis (tendinopathy)2008In: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 331, no 2, p. 385-400Article in journal (Refereed)
    Abstract [en]

    Limited information is available concerning the existence of a cholinergic system in the human Achilles tendon. We have studied pain-free normal Achilles tendons and chronically painful Achilles tendinosis tendons with regard to immunohistochemical expression patterns of the M(2) muscarinic acetylcholine receptor (M(2)R), choline acetyltransferase (ChAT), and vesicular acetylcholine transporter (VAChT). M(2)R immunoreactivity was detected in the walls of blood vessels. As evidenced via parallel staining for CD31 and alpha-smooth muscle actin, most M(2)R immunoreactivity was present in the endothelium. M(2)R immunoreactivity also occured in tenocytes, which regularly immunoreact for vimentin. The degree of M(2)R immunoreactivity was highly variable, tendinosis tendons that exhibit hypercellularity and hypervascularity showing the highest levels of immunostaining. Immunoreaction for ChAT and VAChT was detected in tenocytes in tendinosis specimens, particularly in aberrant cells. In situ hybridization revealed that mRNA for ChAT is present in tenocytes in tendinosis specimens. Our results suggest that autocrine/paracrine effects occur concerning the tenocytes in tendinosis. Up-regulation/down-regulation in the levels of M(2)R immunoreactivity possibly take place in tenocytes and blood vessel cells during the various stages of tendinosis. The presumed local production of acetylcholine (ACh), as evidenced by immunoreactivity for ChAT and VAChT and the detection of ChAT mRNA, appears to evolve in response to tendinosis. These observations are of importance because of the well-known vasoactive, trophic, and pain-modulating effects that ACh is known to have and do unexpectedly establish the presence of a non-neuronal cholinergic system in the Achilles tendon.

  • 111.
    Björklund, Emmelie
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Alfredson, Håkan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Fowler, Christopher J.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Increased expression of cannabinoid CB(1) receptors in achilles tendinosis2011In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 9, p. e24731-Article in journal (Refereed)
    Abstract [en]

    Background: The endogenous cannabinoid system is involved in the control of pain. However, little is known as to the integrity of the cannabinoid system in human pain syndromes. Here we investigate the expression of the cannabinoid receptor 1 (CB(1)) in human Achilles tendons from healthy volunteers and from patients with Achilles tendinosis.

    Methodology: Cannabinoid CB(1) receptor immunoreactivity (CB(1)IR) was evaluated in formalin-fixed biopsies from individuals suffering from painful Achilles tendinosis in comparison with healthy human Achilles tendons.

    Principal Findings: CB(1)IR was seen as a granular pattern in the tenocytes. CB(1)IR was also observed in the blood vessel wall and in the perineurium of the nerve. Quantification of the immunoreactivity in tenocytes showed an increase of CB(1) receptor expression in tendinosis tissue compared to control tissue.

    Conclusion: Expression of cannabinoid receptor 1 is increased in human Achilles tendinosis suggesting that the cannabinoid system may be dysregulated in this disorder.

  • 112.
    Blaszczyk, Izabela
    et al.
    Umeå University. Department of Hand and Plastic Surgery, University Hospital of Northern Sweden, Umeå, Sweden.
    Granström, Anna Cecilia
    Wiberg, Mikael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Department of Hand and Plastic Surgery, University Hospital of Northern Sweden, Umeå, Sweden.
    Denervation of the infraspinatus and release of the posterior deltoid muscles in the management of dyskinetic external shoulder rotation in cerebral palsy2015In: Journal of Neurosurgery: Pediatrics, ISSN 1933-0707, E-ISSN 1933-0715, Vol. 15, no 4, p. 438-444Article in journal (Refereed)
    Abstract [en]

    OBJECT: The dyskinetic subtype of cerebral palsy is difficult to manage, and there is no established gold standard for treatment. External rotation of the shoulder(s) is often managed nonsurgically using injections of botulinum toxin A into the external rotator muscles. This article reports a new surgical technique for managing external rotation when botulinum toxin A treatment is not sufficient or possible.

    METHODS: Six patients with dyskinetic cerebral palsy underwent denervation of the infraspinatus muscle and release of the posterior part of the deltoid muscle. Postoperative questionnaires were given to the patients/caregivers, and video recordings were made both pre- and postoperatively. Preoperative and postoperative Assisting Hand Assessment was possible in only 1 case.

    RESULTS: Five patients were very satisfied with their outcome. Four patients' video recordings showed improvement in their condition. One patient developed postoperative complications.

    CONCLUSIONS: The results indicate that denervation of the infraspinatus muscle and posterior deltoid release can be an option for patients with dyskinetic cerebral palsy to manage external rotation of the shoulder when other treatment alternatives are insufficient.

  • 113.
    Blom, Håkan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Parietal cell regeneration in rat gastric mucosal wounds: a quantitative light and electron microscopical study1982Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aims of the study were to obtain a method with which it would be possible to produce standardized wounds in the gastric mucosa, and to follow the regeneration of the acid producing parietal cells in those lesions during different experimental conditions. Quantitative methods applied to light and electron microscopy were used.

    Wounds were cauterized in the corpus mucosa in Sprague-Dawley rats and in addition, pyloroplasty, truncal vagotomy with pyloroplasty or ant- rectoiriy were performed. Other groups of rats with wounds were given long-term treatment with pentagastrin or cimetidine. Stimulation tests were carried out in two groups of wound operated rats.

    After different periods of time the animals were perfusion fixed and specimens from the wounds and normal mucosa beside the wounds were pre­pared for light and electron microscopy. By means of stereological techniques, different mucosal and cellular structures were then measur­ed.

    Parietal cells were found in 90 days old wounds. At this stage they were immature with large nuclei and few specialized cell organelles. In spite of this appearance they were able to respond morphologically to stimulation and to secrete acid. With further healing the morphology of the parietal cells became normal, but their volume fraction in the mucosa remained subnormal. The fraction of mucosa occupied by epithel­ial cells also stayed lower than normal.

    Pyloroplasty resulted in decreased cell and nuclear size of both normal and regenerating parietal cells. In the latter, there was also a de­crease in the mitochondrial volume density. If a truncal vagotomy was added to the pyloroplasty these changes disappeared and, in addition, an increase in parietal cell volume density was noticed in the normal mucosa.

    Antrectorny produced smaller parietal cells, and their maturation was delayed. Furthermore, mucosal thickness decreased. If pentagastrin was given to rats with wounds an increase in the number of parietal cells was noted, but maturation and morphology remained unaffected.

    Cimetidine treatment did not affect the parietal cell volume density in wounds or normal mucosa. However, a large increase in the secretory surface density was noticed when the effect of the last dose had ceas­ed.

  • 114.
    Blomqvist, Erii
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Regulation of neurotransmission in the central nervous system: What role do presynaptic Cl- transporters play?2016Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 115. Booth, Malcolm G
    et al.
    Hood, John
    Brooks, Timothy J G
    Hart, Andrew
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Glasgow Royal Infirmary, Glasgow, UK; Centre for Cell Engineering, Faculty for Biological & Life Sciences, University of Glasgow, Hillhead, Glasgow, UK.
    Anthrax infection in drug users2010In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 375, no 9723, p. 1345-1346Article in journal (Refereed)
  • 116.
    Boraxbekk, Carl-Johan
    et al.
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Lundquist, Anders
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Nordin, Annelie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Nilsson, Lars-Göran
    Aging Research Center, Karolinska Institutet.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Free Recall Episodic Memory Performance Predicts Dementia 10 Years Prior to Clinical Diagnosis: Findings from the Betula Longitudinal Study2015In: Dementia and geriatric cognitive disorders extra, E-ISSN 1664-5464, Vol. 5, no 2, p. 191-202Article in journal (Refereed)
    Abstract [en]

    Background/Aims: Early dementia diagnosis is a considerable challenge. The present study examined the predictive value of cognitive performance for a future clinical diagnosis of late-onset Alzheimer's disease or vascular dementia in a random population sample. Methods: Cognitive performance was retrospectively compared between three groups of participants from the Betula longitudinal cohort. Group 1 developed dementia 11-22 years after baseline testing (n = 111) and group 2 after 1-10 years (n = 280); group 3 showed no deterioration towards dementia during the study period (n = 2,855). Multinomial logistic regression analysis was used to investigate the predictive value of tests reflecting episodic memory performance, semantic memory performance, visuospatial ability, and prospective memory performance. Results: Age-and education-corrected performance on two free recall episodic memory tests significantly predicted dementia 10 years prior to clinical diagnosis. Free recall performance also predicted dementia 11-22 years prior to diagnosis when controlling for education, but not when age was added to the model. Conclusion: The present results support the suggestion that two free recall-based tests of episodic memory function may be useful for detecting individuals at risk of developing dementia 10 years prior to clinical diagnosis.

  • 117.
    Boraxbekk, Carl-Johan
    et al.
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Salami, Alireza
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Aging Research Center (ARC), Karolinska Institute, Stockholm, Sweden.
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Physical activity over a decade modifies age-related decline in perfusion, gray matter volume, and functional connectivity of the posterior default mode network: a multimodal approach2016In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 131, p. 133-141Article in journal (Refereed)
    Abstract [en]

    One step toward healthy brain aging may be to entertain a physically active lifestyle. Studies investigating physical activity effects on brain integrity have, however, mainly been based on single brain markers, and few used a multimodal imaging approach. In the present study, we used cohort data from the Betula study to examine the relationships between scores reflecting current and accumulated physical activity and brain health. More specifically, we first examined if physical activity scores modulated negative effects of age on seven resting state networks previously identified by Salami, Pudas, and Nyberg (2014). The results revealed that one of the most age-sensitive RSN was positively altered by physical activity, namely, the posterior default-mode network involving the posterior cingulate cortex (PCC). Second, within this physical activity-sensitive RSN, we further analyzed the association between physical activity and gray matter (GM) volumes, white matter integrity, and cerebral perfusion using linear regression models. Regions within the identified DMN displayed larger GM volumes and stronger perfusion in relation to both current and 10-years accumulated scores of physical activity. No associations of physical activity and white matter integrity were observed. Collectively, our findings demonstrate strengthened PCC–cortical connectivity within the DMN, larger PCC GM volume, and higher PCC perfusion as a function of physical activity. In turn, these findings may provide insights into the mechanisms of how long-term regular exercise can contribute to healthy brain aging.

  • 118.
    Borbely, Gabor
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Löfgren, Filip
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Sloniecka, Marta
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Backman, Ludvig J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Danielson, Patrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    The role of neurokinin A in corneal wound repair2015In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 56, no 7, article id Meeting Abstract: 725Article in journal (Other academic)
  • 119. Borg, Kristian
    et al.
    Stucka, Rolf
    Locke, Matthew
    Melin, Eva
    Ahlberg, Gabrielle
    Klutzny, Ursula
    Hagen, Maja von der
    Huebner, Angela
    Lochmüller, Hanns
    Wrogemann, Klaus
    Thornell, Lars-Eric
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Blake, Derek J
    Schoser, Benedikt
    Intragenic deletion of TRIM32 in compound heterozygotes with sarcotubular myopathy/LGMD2H2009In: Human Mutation, ISSN 1059-7794, E-ISSN 1098-1004, Vol. 30, no 9, p. E831-E844Article in journal (Refereed)
    Abstract [en]

    In 2005 the commonality of sarcotubular myopathy (STM) and limb girdle muscular dystrophy type 2H (LGMD2H) was demonstrated, as both are caused by the p D487N missense mutation in TRIM32 originally found in the Manitoba Hutterite population. Recently, three novel homozygous TRIM32 mutations have been described in LGMD patients. Here we describe a three generation Swedish family clinically presenting with limb girdle muscular weakness and histological features of a microvacuolar myopathy. The two index patients were compound heterozygotes for a frameshift mutation in TRIM32 (c.1560delC ) and a 30 kb intragenic deletion, encompassing parts of intron 1 and the entire exon 2 of TRIM32. In these patients, no full-length or truncated TRIM32 could be detected. Interestingly, heterozygous family members carrying only one mutation showed mild clinical symptoms and vacuolar changes in muscle. In our family, the phenotype encompasses additionally a mild demyelinating polyneuropathic syndrome. Thus STM and LGMD2H are the result of loss of function mutations that can be either deletions or missense mutations. (c) 2009 Wiley-Liss, Inc.

  • 120.
    Bourke, Gráinne
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Department of Plastic and Reconstructive Surgery, Leeds Teaching Hospitals Trust, Leeds, UK.
    McGrath, Aleksandra M.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Wiberg, Mikael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences. Department of Plastic and Reconstructive Surgery, Leeds Teaching Hospitals Trust, Leeds, UK.
    Novikov, Lev N.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Effects of early nerve repair on experimental brachial plexus injury in neonatal rats2018In: Journal of Hand Surgery, European Volume, ISSN 1753-1934, E-ISSN 2043-6289, Vol. 43, no 3, p. 275-281Article in journal (Refereed)
    Abstract [en]

    Obstetrical brachial plexus injury refers to injury observed at the time of delivery, which may lead to major functional impairment in the upper limb. In this study, the neuroprotective effect of early nerve repair following complete brachial plexus injury in neonatal rats was examined. Brachial plexus injury induced 90% loss of spinal motoneurons and 70% decrease in biceps muscle weight at 28 days after injury. Retrograde degeneration in spinal cord was associated with decreased density of dendritic branches and presynaptic boutons and increased density of astrocytes and macrophages/microglial cells. Early repair of the injured brachial plexus significantly delayed retrograde degeneration of spinal motoneurons and reduced the degree of macrophage/microglial reaction but had no effect on muscle atrophy. The results demonstrate that early nerve repair of neonatal brachial plexus injury could promote survival of injured motoneurons and attenuate neuroinflammation in spinal cord.

  • 121.
    Bowman, Miles C
    et al.
    Centre for Neuroscience Studies and Department of Psychology, Queen’s University, Kingston, ON K7L 3N6, Canada.
    Johansson, Roland S
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Flanagan, John Randall
    Centre for Neuroscience Studies and Department of Psychology, Queen’s University, Kingston, ON K7L 3N6, Canada.
    Eye-hand coordination in a sequential target contact task2009In: Experimental Brain Research, ISSN 0014-4819, E-ISSN 1432-1106, Vol. 195, no 2, p. 273-283Article in journal (Refereed)
    Abstract [en]

    Most object manipulation tasks involve a series of actions demarcated by mechanical contact events, and gaze is typically directed to the locations of these events as the task unfolds. Here, we examined the timing of gaze shifts relative to hand movements in a task in which participants used a handle to contact sequentially five virtual objects located in a horizontal plane. This task was performed both with and without visual feedback of the handle position. We were primarily interested in whether gaze shifts, which in our task shifted from a given object to the next about 100 ms after contact, were predictive or triggered by tactile feedback related to contact. To examine this issue, we included occasional catch contacts where forces simulating contact between the handle and object were removed. In most cases, removing force did not alter the timing of gaze shifts irrespective of whether or not vision of handle position was present. However, in about 30% of the catch contacts, gaze shifts were delayed. This percentage corresponded to the fraction of contacts with force feedback in which gaze shifted more than 130 ms after contact. We conclude that gaze shifts are predictively controlled but timed so that the hand actions around the time of contact are captured in central vision. Furthermore, a mismatch between the expected and actual tactile information related to the contact can lead to a reorganization of gaze behavior for gaze shifts executed greater than 130 ms after a contact event.

  • 122. Brasselet, R
    et al.
    Johansson, Roland
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Coenen, Olivier
    Arleo, Angelo
    Fast encoding/decoding of haptic microneurography data based on first spike latencies2009In: BMC neuroscience (Online), ISSN 1471-2202, E-ISSN 1471-2202, Vol. 10, no 1, p. 349-350Article in journal (Other academic)
    Abstract [en]

    During haptic exploration tasks, forces are applied to the fingertips, which constitute the most sensitive parts of the hand and are prominently involved in object manipulation/ recognition tasks. The epidermis is innervated with thousands of sensory cells, called mechanoreceptors, that encode the mechanical indentations and deformations of the skin. These cells project directly to a dorsal column nucleus called the cuneate nucleus (CN) that constitutes the first synaptic relay to the central nervous system.

    Recent microneurography studies in humans [1] suggest that the relative timing of impulses from ensembles of mechanoreceptor afferents can convey information about important contact parameters faster than the fastest possible rate code and are fast enough to account for the use of tactile signals in natural manipulation.

    Here, we study a biologically plausible encoding/decoding process accounting for the relative spike timing of the signals propagating from peripheral nerve fibres onto second- order CN neurons. The CN is modelled as a population of 450 spiking neurons receiving as inputs the spatiotemporal responses of real mechanoreceptors obtained via microneurography recordings in humans. An information-theoretic approach is used to quantify the efficiency of the haptic discrimination process. To this extent, a novel entropy definition has been derived analytically.

    This measure proved to be a promising decoding scheme to generalize the classical Shannon's entropy for spiking neural codes, and it allowed us to compute mutual information (MI) in the presence of a large output space (i.e., 450 CN spike train responses) with a 1 ms temporal precision. Using a plasticity rule designed to maximise information transfer explicitly [2], a complete discrimination of 81 distinct stimuli occurred already within 40 ms after the first afferent spike, whereas a partial discrimination (80% of the maximum MI) was possible as rapidly as 20 ms.

    The rationale behind this study was to corroborate our working hypothesis that the CN does not constitute a mere synaptic relay, but it rather conveys an optimal contextual account (in terms of both fast and reliable information transfer) of peripheral tactile inputs to downstream structures (in particular to the thalamus and the cerebellum). Therefore, the CN may play a relevant role in the early processing of haptic information and it would constitute an important component of the haptic classification process (e.g., by facilitating fast discrimination of haptic contexts, minimising destructive interference over lifelong learning, and maximising memorycapacity).

  • 123. Brasselet, Romain
    et al.
    Johansson, Roland
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Arleo, Angelo
    Optimal context separation of spiking haptic signals by second-order somatosensory neurons2009In: Advances in neural information processing systems, Vol. 22, p. 180-188Article in journal (Refereed)
    Abstract [en]

    We study an encoding/decoding mechanism accounting for the relative spike timing of the signals propagating from peripheral nerve fibers to second-order somatosensory neurons in the cuneate nucleus (CN). The CN is modeled as a population of spiking neurons receiving as inputs the spatiotemporal responses of real mechanoreceptors obtained via microneurography recordings in humans. The efficiency of the haptic discrimination process is quantified by a novel definition of entropy that takes into full account the metrical properties of the spike train space. This measure proves to be a suitable decoding scheme for generalizing the classical Shannon entropy to spike-based neural codes. It permits an assessment of neurotransmission in the presence of a large output space (i.e. hundreds of spike trains) with 1 ms temporal precision. It is shown that the CN population code performs a complete discrimination of 81 distinct stimuli already within 35 ms of the first afferent spike, whereas a partial discrimination (80% of the maximum information transmission) is possible as rapidly as 15 ms.

    This study suggests that the CN may not constitute a mere synaptic relay along the somatosensory pathway but, rather, it may convey optimal contextual accounts (in terms of fast and reliable information

    transfer) of peripheral tactile inputs to downstream structures of the central nervous system.

  • 124. Brasselet, Romain
    et al.
    Johansson, Roland S
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Arleo, Angelo
    Isometric coding of spiking haptic signals by peripheral somatosensory2011In: Advances in Computational Intelligence: 11th international work-conference on artificial neural networks, IWANN 2011, Torremolinos-Málaga, Spain, June 8-10, 2011, Proceedings, Part I / [ed] Cabestany, J; Rojas, I; Joya, G, Berlin: Springer Berlin/Heidelberg, 2011, p. 528-536Conference paper (Refereed)
    Abstract [en]

    We study how primary tactile afferents encode relevant contact features to mediate early processing of haptic information. In this paper, we apply metrical information theory to perform temporal decoding of human microneurography data. First, we enrich the theory by deriving a novel spike train metrics inspired by neuronal computation. This spike train metrics can be interpreted biologically and its behaviour is not influenced by spontaneous activity, which decreases the ability of other spike metrics to separate input patterns. Second, we employ our metrical information tools to demonstrate that primary spiking signals allow a putative neural decoder to go beyond stimulus discrimination. They transmit information about geometrical properties of the input space. We show that first-spike latencies are enough to guarantee maximum information transmission of tactile stimuli. However, entire primary spike trains are necessary to encode isometric representations of the stimulus space, a likely basis for generalisation in haptic perception.

  • 125.
    Brasselet, Romain
    et al.
    Université Pierre et Marie Curie, Paris.
    Johansson, Roland S
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Arleo, Angelo
    Université Pierre et Marie Curie, Paris.
    Quantifying neurotransmission reliability through metrics-based information analysis2011In: Neural Computation, ISSN 0899-7667, E-ISSN 1530-888X, Vol. 23, no 4, p. 852-881Article in journal (Refereed)
    Abstract [en]

    We set forth an information-theoretical measure to quantify neurotransmission reliability while taking into full account the metrical properties of the spike train space. This parametric information analysis relies on similarity measures induced by the metrical relations between neural responses as spikes flow in. Thus, in order to assess the entropy, the conditional entropy, and the overall information transfer, this method does not require any a priori decoding algorithm to partition the space into equivalence classes. It therefore allows the optimal parameters of a class of distances to be determined with respect to information transmission. To validate the proposed information-theoretical approach, we study precise temporal decoding of human somatosensory signals recorded using microneurography experiments. For this analysis, we employ a similarity measure based on the Victor-Purpura spike train metrics. We show that with appropriate parameters of this distance, the relative spike times of the mechanoreceptors? responses convey enough information to perform optimal discrimination?defined as maximum metrical information and zero conditional entropy?of 81 distinct stimuli within 40 ms of the first afferent spike. The proposed information-theoretical measure proves to be a suitable generalization of Shannon mutual information in order to consider the metrics of temporal codes explicitly. It allows neurotransmission reliability to be assessed in the presence of large spike train spaces (e.g., neural population codes) with high temporal precision.

  • 126.
    Brohlin, Maria
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Mesenchymal stem cells for repair of the peripheral and central nervous system2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Bone marrow-derived mesenchymal stem cells (MSC) have been shown to provide neuroprotection after transplantation into the injured nervous system. The present thesis investigates whether adult human and rat MSC differentiated along a Schwann cell lineage could increase their expression of neurotrophic factors and promote regeneration after transplantation into the injured peripheral nerve and spinal cord.

    Human and rat mesenchymal stem cells (hMSC and rMSC) expressed characteristic stem cell surface markers, mRNA transcripts for different neurotrophic factors and demonstrated multi-lineage differentiation potential. Following treatment with a cocktail of growth factors, the hMSC and rMSC expressed typical Schwann cells markers at both the transcriptional and translational level and significantly increased production of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF).

    Age and time in culture are of relevance for clinical settings and growth-promoting effects of hMSC from young donors (16-18 years) and old donors (67-75 years) were compared. Undifferentiated hMSC from both young and old donors increased total neurite length of cultured dorsal root ganglion (DRG) neurons. Differentiation of hMSC from the young donors, but not the eldery donors, further enhanced the neurite outgrowth. Undifferentiated hMSC were cultured for eleven weeks in order to examine the effect of in vitro expansion time on neurite outgrowth. hMSC from the young donors maintained their proliferation rate and their ability to enhance neurite outgrowth from DRG neurons.

    Using a sciatic nerve injury model, a 10mm gap was bridged with either an empty tubular fibrin glue conduit, or conduits containing hMSC, with and without cyclosporine treatment. Cells were labeled with PKH26 prior to transplantation. At 3 weeks after injury the conduits with cells and immunosuppression increased regeneration compared with an empty conduit. PKH26 labeled human cells survived in the rat model and the inflammatory reaction could be suppressed by cyclosporine.

    After cervical C4 hemisection, BrdU/GFP-labeled rMSC were injected into the lateral funiculus rostral and caudal to the spinal cord lesion site. Spinal cords were analyzed 2-8 weeks after transplantation. Transplanted MSC remained at the injection sites and in the trauma zone for several weeks and were often associated with numerous neurofilament-positive axons. Transplanted rMSC induced up-regulation of vascular endothelial growth factor in spinal cord tissue rostral to the injury site, but did not affect expression of brain-derived neurotrophic factor. Although rMSC provided neuroprotection for rubrospinal neurons and significantly attenuated astroglial and microglial reaction, cell transplantation caused aberrant sprouting of calcitonin gene-related peptide immunostained sensory axons in the dorsal horn.

    In summary these results demonstrate that both rat and human MSC can be differentiated towards the glial cell lineage, and show functional characteristics similar to Schwann cells. hMSC from the young donors represent a more favorable source for neurotransplantation since they maintain proliferation rate and preserve their growth-promoting effects in long-term cultures. The data also suggest that differentiated MSC increase expression of neurotrophic factors and support regeneration after peripheral nerve and spinal cord injury.

  • 127.
    Brohlin, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Biomedical Laboratory Science.
    Kelk, Peyman
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Wiberg, Mikael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Kingham, Paul J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Effects of a defined xeno-free medium on the growth and neurotrophic and angiogenic properties of human adult stem cells2017In: Cytotherapy, ISSN 1465-3249, E-ISSN 1477-2566, Vol. 19, no 5, p. 629-639Article in journal (Refereed)
    Abstract [en]

    Background. The growth properties and neurotrophic and angiogenic effects of human mesenchymal stromal cells (MSCs) cultured in a defined xeno-free, serum-free medium (MesenCult-XF) were investigated. Methods. Human MSCs from adipose tissue (ASCs) and bone marrow (BMSCs) were cultured in Minimum Essential Medium-alpha (alpha-MEM) containing fetal calf serum or in MesenCult-XF. Proliferation was measured over 10 passages and the colony-forming unit (CFU) assay and expression of cluster of differentiation (CD) surface markers were determined. Neurite outgrowth and angiogenic activity of the MSCs were determined. Results. At early passage, both ASCs and BMSCs showed better proliferation in MesenCult-XF compared with standard a-MEM containing serum. However, CFUs were significantly lower in MesenCult-XF. ASCs cultured in MesenCult-XF continued to expand at faster rates than cells grown in serum. BMSCs showed morphological changes at late passage in MesenCult-XF and stained positive for senescence beta-galactosidase activity. Expression levels of CD73 and CD90 were similar in both cell types under the various culture conditions but CD105 was significantly reduced at passage 10 in MesenCult-XF. In vitro stimulation of the cells enhanced the expression of brain derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF-A) and angiopoietin-1. Stimulated ASCs grown in MesenCult-XF evoked the longest neurite outgrowth in a neuron co-culture model. Stimulated BMSCs grown in MesenCult-XF produced the most extensive network of capillary-like tube structures in an in vitro angiogenesis assay. Conclusions. ASCs and BMSCs exhibit high levels of neurotrophic and angiogenic activity when grown in the defined serum free medium indicating their suitability for treatment of various neurological conditions. However, long-term expansion in MesenCult-XF might be restricted to ASCs.

  • 128.
    Brohlin, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Kingham, Paul
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Novikova, Liudmila
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Novikov, Lev
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Wiberg, Mikael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Aging effect on neurotrophic activity of human mesenchymal stem cells2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 9, p. e45052-Article in journal (Refereed)
    Abstract [en]

    Clinical efficacy of stem cells for nerve repair is likely to be influenced by issues including donor age and in vitro expansion time. We isolated human mesenchymal stem cells (MSC) from bone marrow of young (16–18 years) and old (67–75 years) donors and analyzed their capacity to differentiate and promote neurite outgrowth from dorsal root ganglia (DRG) neurons. Treatment of MSC with growth factors (forskolin, basic fibroblast growth factor, platelet derived growth factor-AA and glial growth factor-2) induced protein expression of the glial cell marker S100 in cultures from young but not old donors. MSC expressed various neurotrophic factor mRNA transcripts. Growth factor treatment enhanced the levels of BDNF and VEGF transcripts with corresponding increases in protein release in both donor cell groups. MSC in co-culture with DRG neurons significantly enhanced total neurite length which, in the case of young but not old donors, was further potentiated by treatment of the MSC with the growth factors. Stem cells from young donors maintained their proliferation rate over a time course of 9 weeks whereas those from the old donors showed increased population doubling times. MSC from young donors, differentiated with growth factors after long-term culture, maintained their ability to enhance neurite outgrowth of DRG. Therefore, MSC isolated from young donors are likely to be a favourable cell source for nerve repair.

  • 129.
    Brohlin, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Mahay, Daljeet
    Novikov, Lev N
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Terenghi, Giorgio
    Wiberg, Mikael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Shawcross, Susan G
    Novikova, Liudmila N
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Characterisation of human mesenchymal stem cells following differentiation into Schwann cell-like cells2009In: Neuroscience research, ISSN 0168-0102, E-ISSN 1872-8111, Vol. 64, no 1, p. 41-49Article in journal (Refereed)
    Abstract [en]

    Cell-based therapies provide a clinically applicable and available alternative to nerve autografts. Our previous studies have characterised rat-derived mesenchymal stem cells (MSC) and here we have investigated the phenotypic, molecular and functional characteristics of human-derived MSC (hMSC) differentiated along a Schwann cell lineage. The hMSC were isolated from healthy human donors and the identity of the undifferentiated hMSC was confirmed by the detection of MSC specific cells surface markers. The hMSC were differentiated along a glial cell lineage using an established cocktail of growth factors including glial growth factor-2. Following differentiation, the hMSC expressed the key Schwann cell (SC) markers at both the transcriptional and translational level. More importantly, we show the functional effect of hMSC on neurite outgrowth using an in vitro co-culture model system with rat-derived primary sensory neurons. The number of DRG sprouting neurites was significantly enhanced in the presence of differentiated hMSC; neurite length and density (branching) were also increased. These results provide evidence that hMSC can undergo molecular, morphological and functional changes to adopt a SC-like behaviour and, therefore, could be suitable as SC substitutes for nerve repair in clinical applications.

  • 130. Broom, Oliver Jay
    et al.
    Zhang, Yuan
    Oldenborg, Per-Arne
    Umeå University, Faculty of Medicine, Integrative Medical Biology.
    Massoumi, Ramin
    Sjölander, Anita
    CD47 regulates collagen I-induced cyclooxygenase-2 expression and intestinal epithelial cell migration.2009In: PloS one, ISSN 1932-6203, Vol. 4, no 7, p. e6371-Article in journal (Refereed)
    Abstract [en]

    Increased epithelial cell expression of the cyclooxygenase-2 (COX-2) enzyme is a characteristic event of both inflammatory bowel disease and colon cancer. We here report the novel findings that collagen I-induced de novo synthesis of COX-2 in intestinal epithelial cells is inhibited by pertussis toxin (PTX) and by an inhibitory peptide selective for the heterotrimeric G alpha(i3)-protein. These findings could be explained by a regulatory involvement of the G-protein-dependent integrin-associated protein CD47. In support of this notion, we observed a collagen I-induced association between CD47 and alpha2 integrins. This association was reduced by a blocking anti-CD47 antibody but not by PTX or a control anti-beta2 antibody. Furthermore, a blocking antibody against CD47, dominant negative CD47 or specific siRNA knock down of CD47, significantly reduced collagen I-induced COX-2 expression. COX-2 has previously been shown to regulate intestinal epithelial cell adhesion and migration. Morphological analysis of intestinal cells adhering to collagen I revealed a co-localisation of CD47 and alpha2 integrins to non-apoptotic membrane blebs enriched in Rho A and F-actin. The blocking CD47 antibody, PTX and a selective COX-2 inhibitor, dramatically inhibited the formation of these blebs. In accordance, migration of these cells on a collagen I-coated surface or through a collagen I gel were significantly reduced by the CD47 blocking antibody, siRNA knock down of CD47 and the COX-2 inhibitor NS-398. In conclusion, we present novel data that identifies the G-protein-dependent CD47 protein as a key regulator of collagen I-induced COX-2 expression and a promoter of intestinal epithelial cell migration.

  • 131. Bruce, Lesley J
    et al.
    Ghosh, Sandip
    King, May Jean
    Layton, D Mark
    Mawby, William J
    Stewart, Gordon W
    Oldenborg, Per-Arne
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Histology and Cell Biology.
    Delaunay, Jean
    Tanner, Michael J A
    Absence of CD47 in protein 4.2-deficient hereditary spherocytosis in man: an interaction between the Rh complex and the band 3 complex.2002In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 100, no 5, p. 1878-1885Article in journal (Refereed)
    Abstract [en]

    We present data on a patient of South Asian origin with recessive hereditary spherocytosis (HS) due to absence of protein 4.2 [4.2 (-) HS]. Protein 4.2 cDNA sequence analysis showed the presence of a novel 41-bp frameshift deletion that predicts a truncated peptide designated protein 4.2 Hammersmith. Quantitative reverse transcription-polymerase chain reaction indicated that the mutant mRNA was unstable. Sequencing of protein 4.2 genomic DNA revealed that the deletion stems from aberrant splicing. The proband was homozygous for a G>T substitution at position 1747 (cDNA numbering) that activates a cryptic acceptor splice site within exon 11 of the protein 4.2 gene (EPB42). The proband's mother was found to be heterozygous for this substitution. Unlike protein 4.2 null mice, the proband's red cells showed no evidence for abnormal cation permeability. Quantitation of red cell membrane proteins was carried out by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), Western blotting, and flow cytometric measurement. CD47, a protein associated with the Rh complex, was markedly reduced to about 1% (in the proband) and 65% (in the mother) that found in healthy controls. The Rh-associated glycoprotein migrated with a higher than normal apparent molecular weight on SDS-PAGE. There was no obvious reduction in Rh polypeptides. These observations indicate that protein 4.2 and CD47 interact in the human red cell membrane. They provide further evidence for an association between the band 3 complex (band 3, ankyrin, protein 4.2, glycophorin A) and the Rh complex (Rh-associated glycoprotein, Rh polypeptides, glycophorin B, CD47, LW) and define a point of attachment between the Rh complex and the red cell cytoskeleton.

  • 132. Brys, Ivani
    et al.
    Halje, Par
    Scheffer-Teixeira, Robson
    Varney, Mark
    Newman-Tancredi, Adrian
    Petersson, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Integrative Neurophysiology and Neurotechnology, Neuronano Research Center, Department of Experimental Medical Sciences, Lund University, Sweden.
    Neurophysiological effects in cortico-basal ganglia-thalamic circuits of antidyskinetic treatment with 5-HT1A receptor biased agonists2018In: Experimental Neurology, ISSN 0014-4886, E-ISSN 1090-2430, Vol. 302, p. 155-168Article in journal (Refereed)
    Abstract [en]

    Recently, the biased and highly selective 5-HT1A agonists, NLX-112, F13714 and F15599, have been shown to alleviate dyskinesia in rodent and primate models of Parkinson's disease, while marginally interfering with antiparkinsonian effects of levodopa. To provide more detailed information on the processes underlying the alleviation of dyskinesia, we have here investigated changes in the spectral contents of local field potentials in cortico-basal ganglia-thalamic circuits following treatment with this novel group of 5-HT1A agonists or the prototypical agonist, 8-OH-DPAT. Dyskinetic symptoms were consistently associated with 80 Hz oscillations, which were efficaciously suppressed by all 5-HT1A agonists and reappeared upon co-administration of the antagonist, WAY100635. At the same time, the peak-frequency of fast 130 Hz gamma oscillations and their cross-frequency coupling to low-frequency delta oscillations were modified to a different extent by each of the 5-HT1A agonists. These findings suggest that the common antidyskinetic effects of these drugs may be chiefly attributable to a reversal of the brain state characterized by 80 Hz gamma oscillations, whereas the differential effects on fast gamma oscillations may reflect differences in pharmacological properties that might be of potential relevance for non-motor symptoms.

  • 133.
    Burstedt, Magnus K
    et al.
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Birznieks, Ingvars
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Edin, Benoni B
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Johansson, Roland S
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Control of forces applied by individual fingers engaged in restraint of an active object.1997In: Journal of Neurophysiology, ISSN 0022-3077, E-ISSN 1522-1598, Vol. 78, no 1, p. 117-128Article in journal (Refereed)
    Abstract [en]

    We investigated the coordination of fingertip forces in subjects who used the tips of two fingers to restrain an instrumented manipulandum with horizontally oriented grip surfaces. The grip surfaces were subjected to tangential pulling forces in the distal direction in relation to the fingers. The subjects used either the right index and middle fingers (unimanual grasp) or both index fingers (bimanual grasp) to restrain the manipulandum. To change the frictional condition at the digit-object interfaces, either both grip surfaces were covered with sandpaper or one was covered with sandpaper and the other with rayon. The forces applied normally and tangentially to the grip surfaces were measured separately at each plate along with the position of the plates. Subjects could have performed the present task successfully with many different force distributions between the digits. However, they partitioned the load in a manner that reflected the frictional condition at the local digit-object interfaces. When both digits contacted sandpaper, they typically partitioned the load symmetrically, but when one digit made contact with rayon and the other with sandpaper, the digit contacting the less slippery material (sandpaper) took up a larger part of the load. The normal forces were also influenced by the frictional condition, but they reflected the average friction at the two contact sites rather than the local friction. That is, when friction was low at one of the digit-object interfaces, only the applied normal forces increased at both digits. Thus sensory information related to the local frictional condition at the respective digit-object interfaces controlled the normal force at both digits. The normal:tangential force ratio at each digit appeared to be a controlled variable. It was adjusted independently at each digit to the minimum ratio required to prevent frictional slippage, keeping an adequate safety margin against slippage. This was accomplished by the scaling of the normal forces to the average friction and by partitioning of the load according to frictional differences between the digit-object interfaces. In conclusion, by adjusting the normal:tangential force ratios to the local frictional condition, subjects avoided excessive normal forces at the individual digit-object interfaces, and by partitioning the load according the frictional difference, subjects avoided high normal forces. Thus the local frictional condition at the separate digit-object interfaces is one factor that can strongly influence the distribution of forces across digits engaged in a manipulative act.

  • 134.
    Burstedt, Magnus K
    et al.
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Edin, Benoni B
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Johansson, Roland S
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Coordination of fingertip forces during human manipulation can emerge from independent neural networks controlling each engaged digit.1997In: Experimental Brain Research, ISSN 0014-4819, E-ISSN 1432-1106, Vol. 117, no 1, p. 67-79Article in journal (Refereed)
    Abstract [en]

    We investigated the coordination of fingertip forces in subjects who lifted an object (i) using the index finger and thumb of their right hand, (ii) using their left and right index fingers, and (iii) cooperatively with another subject using the right index finger. The forces applied normal and tangential to the two parallel grip surfaces of the test object and the vertical movement of the object were recorded. The friction between the object and the digits was varied independently at each surface between blocks of trials by changing the materials covering the grip surfaces. The object's weight and surface materials were held constant across consecutive trials. The performance was remarkably similar whether the task was shared by two subjects or carried out unimanually or bimanually by a single subject. The local friction was the main factor determining the normal:tangential force ratio employed at each digit-object interface. Irrespective of grasp configuration, the subjects adapted the force ratios to the local frictional conditions such that they maintained adequate safety margins against slips at each of the engaged digits during the various phases of the lifting task. Importantly, the observed force adjustments were not obligatory mechanical consequences of the task. In all three grasp configurations an incidental slip at one of the digits elicited a normal force increase at both engaged digits such that the normal:tangential force ratio was restored at the non-slipping digit and increased at the slipping digit. The initial development of the fingertip forces prior to object lift-off revealed that the subjects employed digit-specific anticipatory mechanisms using weight and frictional experiences in the previous trial. Because grasp stability was accomplished in a similar manner whether the task was carried out by one subject or cooperatively by two subjects, it was concluded that anticipatory adjustments of the fingertip forces can emerge from the action of anatomically independent neural networks controlling each engaged digit. In contrast, important aspects of the temporal coordination of the digits was organized by a "higher level" sensory-based control that influenced both digits. In lifts by single subjects this control was mast probably based on tactile and visual input and on communication between neural control mechanisms associated with each digit. In the two-subject grasp configuration this synchronization information was based on auditory and visual cues.

  • 135.
    Burzynska, A Z
    et al.
    Max Planck Institute for Human Development, Berlin.
    Preuschhof, C
    Max Planck Institute for Human Development, Berlin.
    Bäckman, L
    Max Planck Institute for Human Development, Berlin, Karolinska Institute.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Li, S-C
    Max Planck Institute for Human Development, Berlin.
    Lindenberger, U
    Max Planck Institute for Human Development, Berlin, .
    Heekeren, H R
    Max Planck Institute for Human Development, Berlin, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig.
    Age-related differences in white matter microstructure: region-specific patterns of diffusivity.2010In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 49, no 3, p. 2104-2112Article in journal (Refereed)
    Abstract [en]

    We collected MRI diffusion tensor imaging data from 80 younger (20-32 years) and 63 older (60-71 years) healthy adults. Tract-based spatial statistics (TBSS) analysis revealed that white matter integrity, as indicated by decreased fractional anisotropy (FA), was disrupted in numerous structures in older compared to younger adults. These regions displayed five distinct region-specific patterns of age-related differences in other diffusivity properties: (1) increases in both radial and mean diffusivity; (2) increases in radial diffusivity; (3) no differences in parameters other than FA; (4) a decrease in axial and an increase in radial diffusivity; and (5) a decrease in axial and mean diffusivity. These patterns suggest different biological underpinnings of age-related decline in FA, such as demyelination, Wallerian degeneration, gliosis, and severe fiber loss, and may represent stages in a cascade of age-related degeneration in white matter microstructure. This first simultaneous description of age-related differences in FA, mean, axial, and radial diffusivity requires histological and functional validation as well as analyses of intermediate age groups and longitudinal samples.

  • 136. Button, J.
    et al.
    Scott, J.
    Taghizadeh, R.
    Weiler-Mithoff, E.
    Hart, Andrew M.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Canniesburn Plastic Surgery Unit, Glasgow Royal Infirmary, 84 Castle Street, Glasgow G4 0SF, UK; Department of Surgical and Perioperative Science, Section for Hand & Plastic Surgery, University Hospital, Umea, Sweden.
    Shoulder function following autologous latissimus dorsi breast reconstruction: A prospective three year observational study comparing quilting and non-quilting donor site techniques2010In: Journal of Plastic, Reconstructive & Aesthetic Surgery, ISSN 1748-6815, E-ISSN 1532-1959, Vol. 63, no 9, p. 1505-1512Article in journal (Refereed)
    Abstract [en]

    Latissimus dorsi harvest and axillary surgery can affect shoulder function. The effect of autologous latissimus dorsi flap (ALD) breast reconstruction and donor site quilting have been inadequately studied. A cohort of ALD flap breast reconstruction patients were assessed pre-operatively and at eight post-operative time-points (up to 3 years after reconstruction) using the self-administered Disabilities of the Arm, Shoulder and Hand (DASH) outcome measure, for which validated normative data is available. Patients with incidental shoulder conditions and bilateral reconstructions were excluded. This was a prospective, observational study with blinded data interpretation: 58 patients, 22 of whom had donor site quilting, were assessed. Groups were compatible demographically, in breast care management and in pre-operative DASH score (quilted 6.5, non-quilted 6.4; P = 0.98). Scores were significantly increased at initial post-operative clinic review (mean 49, SD19; P < 0.001), 6 week (29, SD20; P < 0.001), and 3 month (19, SD19; P < 0.01), thereafter remaining at a plateau value of similar to 15 (P > 0.05). Seroma incidence was reduced in the quilted group (5% vs 70%). A strong, significant correlation was found between 3 month DASH score and long term function (r = 0.66, P < 0.0003); patients with DASH > 20 fare significantly worse in the long-term (mean 20 point increase, SD5.0, P < 0.001). Higher post-operative DASH scores correlated significantly with pre-operative DASH (r = 0.58) and BMI (r = 0.36). Adjuvant therapy had no effect on shoulder function. Axillary dissection had a weak correlation with a higher DASH score, but only at the 3-month post-operative time-point (r = 0.32, P = 0.03). ALD flap breast reconstruction generally results in a functionally insignificant increase (6.5 points) in longterm DASH score, although a small subset of patients do develop longterm impairment, and quilting does not appear to inhibit shoulder function. (C) 2009 British Association of Plastic, Reconstructive and Aesthetic Surgeons.

  • 137.
    Byström, Berit
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Carracedo, Sergio
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Gullberg, Donald
    Pedrosa-Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Alpha11 integrin in the human cornea: importance in development and disease.2009In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 50, no 11, p. 5044-5053Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To examine the distribution of the alpha11 integrin chain in the human cornea during fetal development and in normal and diseased adult human corneas.

    METHODS: Six fetal corneas, 10 to 20 weeks of gestation (wg), and 18 adult corneas including 3 normal, 7 with keratoconus, 5 with pseudophakic bullous keratopathy (PBK), 2 with Fuchs' corneal dystrophy, and 1 with a scar after deep lamellar keratoplasty (DLKP) were processed for immunohistochemistry with specific antibodies against the alpha11 integrin chain; collagen I, IV, and V; and alpha-smooth muscle actin (alpha-SMA). The cellular source of alpha11 integrin chain was further investigated in cell cultures.

    RESULTS: At 10 to 17 wg, the alpha11 integrin chain was predominantly present in the anterior corneal stroma. At 20 wg, in normal adult corneas and in Fuchs' dystrophy corneas there was weak staining in the stroma. The PBK corneas showed variable and weak staining, generally accentuated in the posterior stroma near Descemet's membrane. In contrast, the anterior portion of the stroma in the keratoconus corneas was strongly stained in an irregular streaky pattern. Human corneal fibroblasts/myofibroblasts produced alpha11 integrin chain in culture. Cultures treated with TGF-beta showed higher content of both alpha-SMA and the alpha11 integrin chain.

    CONCLUSIONS: The presence of the alpha11 integrin chain during early corneal development and the enhanced expression in scarred keratoconus corneas indicates that this integrin chain is likely to play an important role in collagen deposition during corneal development and in keratoconus with a scarring component and compromised basement membrane integrity.

  • 138.
    Byström, Berit
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Virtanen, Ismo
    Rousselle, Patricia
    Gullberg, Donald
    Pedrosa-Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Distribution of laminins in the developing human eye2006In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 47, no 3, p. 777-785Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To examine the distribution of laminin (Ln) chains in basement membranes (BMs) of the human cornea, lens, and retina in fetal development. METHODS: Ten fetal eyes (9-20 weeks of gestation [wg]) were serially sectioned and treated with specific antibodies against the Ln-alpha1, -alpha2, -alpha3, -alpha4, -alpha5, -beta1, -beta2, -beta3, and -gamma1 chains. RESULTS: The BM of the corneal epithelium was reactive for Ln-alpha3, -alpha5, -beta1, and beta3 chains through all ages, whereas the Ln-alpha1 chain was present at 9 to 12 wg and the Ln-alpha4 chain from 10 wg. The Descemet's membrane (DM) was labeled with the Ln-alpha1 and -alpha4 chains at 10 to 17 wg, the Ln-alpha5 chain from 10 wg, the Ln-beta1 chain at 11 to 17 wg, and the Ln-beta3 chain from 17 wg. The Ln-alpha1, alpha5, -beta1, and -beta2 chains were present in the lens capsule and the internal limiting membrane (ILM) through all ages. The Bruch's membrane (BrM) was immunoreactive for the Ln-alpha3, alpha4, -alpha5, -beta1, and -beta2 chains through all ages, whereas the Ln-alpha1 chain was absent from 20 wg onward. The Ln-alpha2 chain was not detected in the eye, but it was present in the extraocular muscles. CONCLUSIONS: BMs play an important role during morphogenesis, in that they influence cell proliferation, migration, and tissue differentiation. Lns are the major noncollagenous component of BMs. The presence of four different alpha chains, three beta chains, and one gamma chain of Ln in the eye reveals a high degree of complexity from the early stages of development and suggests an important role for the different Ln chains in human ocular differentiation.

  • 139.
    Byström, Berit
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Virtanen, Ismo
    Rousselle, Patricia
    Miyazaki, Kaoru
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Pedrosa-Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Laminins in normal, keratoconus, bullous keratopathy and scarred human corneas2007In: Histochemistry and Cell Biology, ISSN 0948-6143, E-ISSN 1432-119X, Vol. 127, no 6, p. 657-667Article in journal (Refereed)
    Abstract [en]

    The laminin composition (LMalpha1-alpha5, beta1-beta3, gamma1 and gamma2 chains) of normal corneas and corneal buttons from keratoconus, bullous keratopathy (BKP), Fuchs' dystrophy + BKP, Fuchs' dystrophy without BKP and scar after deep lamellar keratoplasty (DLKP) was investigated with immunohistochemistry. The epithelial basement membranes (BMs) of both normal and diseased corneas contained LMalpha3, alpha5, beta1, beta3, gamma1 and gamma2 chains. The epithelial BM morphology was altered in the different diseases. Scarring was associated with irregular BM and ectopic stromal localization of different laminin chains. The Descemet's membrane (DM) contained LMalpha5, beta1 and gamma1 chains in all cases and additionally LMbeta3 and gamma2 chains in the majority of keratoconus corneas. The interface in the DLKP cornea had patches of LMalpha3, alpha4, alpha5, beta1 and beta2 chains, and an extra BM-like structure under the Bowman's membrane. These results suggest that laminin chains participate in the process of corneal scarring and in the pathogenesis of some corneal diseases. The novel finding of LMalpha3, beta3 and gamma2 in the DM of keratoconus buttons indicates that this membrane is also involved in the disease and that some cases of keratoconus may have a congenital origin, without normal downregulation of the LMbeta3 chain.

  • 140.
    Bäckman, Lars
    et al.
    Aging Research Center, Karolinska Institutet, Gävlegatan 16, SE-113 30 Stockholm, Sweden.
    Karlsson, Sari
    Aging Research Center, Karolinska Institutet, Gävlegatan 16, SE-113 30 Stockholm, Sweden.
    Fischer, Håkan
    Aging Research Center, Karolinska Institutet, Gävlegatan 16, SE-113 30 Stockholm, Sweden.
    Karlsson, Per
    Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet, Stockholm, Sweden.
    Brehmer, Yvonne
    Aging Research Center, Karolinska Institutet, Gävlegatan 16, SE-113 30 Stockholm, Sweden.
    Rieckmann, Anna
    Aging Research Center, Karolinska Institutet, Gävlegatan 16, SE-113 30 Stockholm, Sweden.
    Macdonald, Stuart WS
    Aging Research Center, Karolinska Institutet, Gävlegatan 16, SE-113 30 Stockholm, Sweden; Department of Psychology, University of Victoria, Canada .
    Farde, Lars
    Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet, Stockholm, Sweden.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Dopamine D(1) receptors and age differences in brain activation during working memory2011In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 32, no 10, p. 1849-1856Article in journal (Refereed)
    Abstract [en]

    In an fMRI study, 20 younger and 20 healthy older adults were scanned while performing a spatial working-memory task under two levels of load. On a separate occasion, the same subjects underwent PET measurements using the radioligand [(11)C] SCH23390 to determine dopamine D(1) receptor binding potential (BP) in caudate nucleus and dorsolateral prefrontal cortex (DLPFC). The fMRI study revealed a significant load modulation of brain activity (higher load>lower load) in frontal and parietal regions for younger, but not older, adults. The PET measurements showed marked age-related reductions of D(1) BP in caudate and DLPFC. Statistical control of caudate and DLPFC D(1) binding eliminated the age-related reduction in load-dependent BOLD signal in left frontal cortex, and attenuated greatly the reduction in right frontal and left parietal cortex. These findings suggest that age-related alterations in dopaminergic neurotransmission may contribute to underrecruitment of task-relevant brain regions during working-memory performance in old age.

  • 141. Bäckman, Lars
    et al.
    Lindenberger, Ulman
    Li, Shu-Chen
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Linking cognitive aging to alterations in dopamine neurotransmitter functioning: Recent data and future avenues2010In: Neuroscience and Biobehavioral Reviews, ISSN 0149-7634, E-ISSN 1873-7528, Vol. 34, no 5, p. 670-677Article, review/survey (Refereed)
    Abstract [en]

    Molecular-imaging studies of dopaminergic neurotransmission measure biomarkers of dopamine (DA), such as the DA transporter and D(1) and D(2) receptor densities in the living brain. These studies indicate that individual differences in DA functions are linked to cognitive performance irrespective of age, and serve as powerful mediators of age-related decline in executive functioning, episodic memory, and perceptual speed. This focused review targets several recent findings pertaining to these relationships. Specifically, we discuss novel evidence concerning (a) the role of DA in within-person cognitive variability; (b) age-related differences in DA release during cognitive processing; (c) DA release following cognitive training in younger and older adults; and (d) the relationship between DA and task-induced functional brain activity. Based on these lines of empirical inquiry, we outline a series of avenues for future research on aging, DA, and cognition.

  • 142. Bäckman, Lars
    et al.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Lindenberger, Ulman
    Li, Shu-Chen
    Farde, Lars
    The correlative triad among aging, dopamine, and cognition: current status and future prospects.2006In: Neuroscience and Biobehavioral Review, ISSN 0149-7634, Vol. 30, no 6, p. 791-807Article in journal (Other academic)
    Abstract [en]

    The brain neuronal systems defined by the neurotransmitter dopamine (DA) have since long a recognized role in the regulation of motor functions. More recently, converging evidence from patient studies, animal research, pharmacological intervention, and molecular genetics indicates that DA is critically implicated also in higher-order cognitive functioning. Many cognitive functions and multiple markers of striatal and extrastriatal DA systems decline across adulthood and aging. Research examining the correlative triad among adult age, DA, and cognition has found strong support for the view that age-related DA losses are associated with age-related cognitive deficits. Future research strategies for examining the DA-cognitive aging link include assessing (a) the generality/specificity of the effects; (b) the relationship between neuromodulation and functional brain activation; and (c) the release of DA during actual task performance.

  • 143.
    Bäckman, Lars
    et al.
    Aging Research Center, Karolinska Institute, Stockholm, Sweden.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Soveri, Anna
    Department of Psychology and Logopedics, Åbo Akademi University, Turku, Finland.
    Johansson, Jarkko
    Turku PET Center, University of Turku, Turku, Finland.
    Andersson, Micael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Dahlin, Erika
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Neely, Anna S
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Virta, Jere
    Turku PET Center, University of Turku, Turku, Finland.
    Laine, Matti
    Department of Psychology and Logopedics, Åbo Akademi University, Turku, Finland.
    Rinne, Juha O
    Turku PET Center, University of Turku, Turku, Finland.
    Effects of working-memory training on striatal dopamine release2011In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 333, no 6043, p. 718-Article in journal (Refereed)
    Abstract [en]

    Updating of working memory has been associated with striato-frontal brain regions and phasic dopaminergic neurotransmission. We assessed raclopride binding to striatal dopamine (DA) D2 receptors during a letter-updating task and a control condition before and after 5 weeks of updating training. Results showed that updating affected DA activity before training and that training further increased striatal DA release during updating. These findings highlight the pivotal role of transient neural processes associated with D2 receptor activity in working memory.

  • 144. Bäckman, Lars
    et al.
    Waris, Otto
    Johansson, Jarkko
    Andersson, Micael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Rinne, Juha O.
    Alakurtti, Kati
    Soveri, Anna
    Laine, Matti
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Increased dopamine release after working-memory updating training: Neurochemical correlates of transfer2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 7160Article in journal (Refereed)
    Abstract [en]

    Previous work demonstrates that working-memory (WM) updating training results in improved performance on a letter-memory criterion task, transfers to an untrained n-back task, and increases striatal dopamine (DA) activity during the criterion task. Here, we sought to replicate and extend these findings by also examining neurochemical correlates of transfer. Four positron emission tomography (PET) scans using the radioligand raclopride were performed. Two of these assessed DAD2 binding (letter memory; n-back) before 5 weeks of updating training, and the same two scans were performed post training. Key findings were (a) pronounced training-related behavioral gains in the lettermemory criterion task, (b) altered striatal DAD2 binding potential after training during letter-memory performance, suggesting training-induced increases in DA release, and (c) increased striatal DA activity also during the n-back transfer task after the intervention, but no concomitant behavioral transfer. The fact that the training-related DA alterations during the transfer task were not accompanied by behavioral transfer suggests that increased DA release may be a necessary, but not sufficient, condition for behavioral transfer to occur.

  • 145. Cabeza, Roberto
    et al.
    Albert, Marilyn
    Belleville, Sylvie
    Craik, Fergus I. M.
    Duarte, Audrey
    Grady, Cheryl L.
    Lindenberger, Ulman
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Park, Denise C.
    Reuter-Lorenz, Patricia A.
    Rugg, Michael D.
    Steffener, Jason
    Rajah, M. Natasha
    Maintenance, reserve and compensation: the cognitive neuroscience of healthy ageing2018In: Nature Reviews Neuroscience, ISSN 1471-003X, E-ISSN 1471-0048, Vol. 19, no 11, p. 701-710Article, review/survey (Refereed)
    Abstract [en]

    Cognitive ageing research examines the cognitive abilities that are preserved and/or those that decline with advanced age. There is great individual variability in cognitive ageing trajectories. Some older adults show little decline in cognitive ability compared with young adults and are thus termed ‘optimally ageing’. By contrast, others exhibit substantial cognitive decline and may develop dementia. Human neuroimaging research has led to a number of important advances in our understanding of the neural mechanisms underlying these two outcomes. However, interpreting the age-related changes and differences in brain structure, activation and functional connectivity that this research reveals is an ongoing challenge. Ambiguous terminology is a major source of difficulty in this venture. Three terms in particular — compensation, maintenance and reserve — have been used in a number of different ways, and researchers continue to disagree about the kinds of evidence or patterns of results that are required to interpret findings related to these concepts. As such inconsistencies can impede progress in both theoretical and empirical research, here, we aim to clarify and propose consensual definitions of these terms.

  • 146. Cabeza, Roberto
    et al.
    Daselaar, Sander M
    Dolcos, Florin
    Prince, Steven E
    Budde, Matthew
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology. Umeå University, Faculty of Social Sciences, Department of Psychology.
    Task-independent and task-specific age effects on brain activity during working memory, visual attention and episodic retrieval.2004In: Cerebral Cortex, ISSN 1047-3211, Vol. 14, no 4, p. 364-75Article in journal (Refereed)
    Abstract [en]

    It is controversial whether the effects of aging on various cognitive functions have the same common cause or several different causes. To investigate this issue, we scanned younger and older adults with functional magnetic resonance imaging (fMRI) while performing three different tasks: working memory, visual attention and episodic retrieval. There were three main results. First, in all three tasks, older adults showed weaker occipital activity and stronger prefrontal and parietal activity than younger adults. The occipital reduction is consistent with the view that sensory processing decline is a common cause in cognitive aging, and the prefrontal increase may reflect functional compensation. Secondly, older adults showed more bilateral patterns of prefrontal activity than younger adults during working memory and visual attention tasks. These findings are consistent with the Hemispheric Asymmetry Reduction in Older Adults (HAROLD) model. Finally, compared to younger adults, older adults showed weaker hippocampal formation activity in all three tasks but stronger parahippocampal activity in the episodic retrieval task. The former finding suggests that age-related hippocampal deficits may have a global effect in cognition, and the latter is consistent with an age-related increase in familiarity-based recognition. Taken together, the results indicate that both common and specific factors play an important role in cognitive aging.

  • 147. Cabeza, Roberto
    et al.
    Nyberg, LarsUmeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.Park, Denise
    Cognitive neuroscience of aging: linking cognitive and cerebral aging2005Collection (editor) (Other academic)
    Abstract [en]

    Until recently, the cognitive and neural mechanisms of age-related changes in cognition were usually studied independently of each other.

    On one hand, studies in the domain of cognitive psychology of aging investigated the effects of aging on behavioral measures of cognition and characterized a variety of age-related deficits in memory, attention, and the like. On the other hand, studies in the domain of neuroscience of aging investigated the effects of aging on the anatomy and physiology of the brain and described forms of age-related neural decline, such as cerebral atrophy and synaptic loss. Although it is reasonable to assume that cognitive aging is largely a consequence of cerebral aging, the relationships between these two phenomena are still largely unknown. Fortunately, this void is being rapidly resolved by studies focusing on the relationships between the effects of aging on the cognition and on the brain. This group of studies constitutes the new discipline of cognitive neuroscience of aging (CNA). Although CNA has a long past, only lately has it achieved the critical mass to be considered an autonomous discipline. The main goal of this book is to provide an introduction to this exciting new field.

  • 148. Caddick, Jenny
    et al.
    Kingham, Paul J
    Gardiner, Natalie J
    Wiberg, Mikael
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Anatomy. Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Hand Surgery.
    Terenghi, Giorgio
    Phenotypic and functional characteristics of mesenchymal stem cells differentiated along a Schwann cell lineage.2006In: Glia, ISSN 0894-1491, E-ISSN 1098-1136, Vol. 54, no 8, p. 840-849Article in journal (Refereed)
    Abstract [en]

    We have investigated the phenotypic and bioassay characteristics of bone marrow mesenchymal stromal cells (MSCs) differentiated along a Schwann cell lineage using glial growth factor. Expression of the Schwann cell markers S100, P75, and GFAP was determined by immunocytochemical staining and Western blotting. The levels of the stem cell markers Stro-1 and alkaline phosphatase and the neural progenitor marker nestin were also examined throughout the differentiation process. The phenotypic properties of cells differentiated at different passages were also compared. In addition to a phenotypic characterization, the functional ability of differentiated MSCs has been investigated employing a co-culture bioassay with dissociated primary sensory neurons. Following differentiation, MSCs underwent morphological changes similar to those of cultured Schwann cells and stained positively for all three Schwann cell markers. Quantitative Western blot analysis showed that the levels of S100 and P75 protein were significantly elevated upon differentiation. Differentiated MSCs were also found to enhance neurite outgrowth in co-culture with sensory neurons to a level equivalent or superior to that produced by Schwann cells. These findings support the assertion that MSCs can be differentiated into cells that are Schwann cell-like in terms of both phenotype and function.

  • 149.
    Carlsson, Lena
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    The muscle cytoskeleton of mice and men: Structural remodelling in desmin myopathies2001Doctoral 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.

  • 150.
    Carlsson, Lena
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Fischer, Christine
    Karoloinska Institute.
    Sjöberg, Gunnnar
    Karoloinska Institute.
    Robson, Richard M
    Iowa Statte University.
    Sejersen, Thomas
    Karoloinska Institute.
    Thornell, Lars-Eric
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Cytoskeletal derangements in hereditary myopathy with a desmin L345P mutation2002In: Acta Neuropathologica, ISSN 0001-6322, E-ISSN 1432-0533, Vol. 104, no 5, p. 493-504Article in journal (Refereed)
    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.

1234567 101 - 150 of 1290
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf