7 results on '"Pontén, Eva"'
Search Results
2. Extracellular vesicle characteristics and microRNA content in cerebral palsy and typically developed individuals at rest and in response to aerobic exercise
- Author
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Vechetti, Ivan J., Norrbom, Jessica, Alkner, Björn, Hjalmarsson, Emma, Palmcrantz, Alexandra, Pontén, Eva, Pingel, Jessica, von Walden, Ferdinand, and Fernandez-Gonzalo, Rodrigo
- Subjects
exosomes ,endurance exercise ,miR-486 ,skeletal muscle ,frame running ,Idrottsvetenskap ,Sport and Fitness Sciences - Abstract
In this study, the properties of circulating extracellular vesicles (EVs) were examined in cerebral palsy (CP) and typically developed (TD) individuals at rest and after aerobic exercise, focusing on the size, concentration, and microRNA cargo of EVs. Nine adult individuals with CP performed a single exercise bout consisting of 45 min of Frame Running, and TD participants completed either 45 min of cycling (n = 10; TD EX) or were enrolled as controls with no exercise (n = 10; TD CON). Blood was drawn before and 30 min after exercise and analyzed for EV concentration, size, and microRNA content. The size of EVs was similar in CP vs. TD, and exercise had no effect. Individuals with CP had an overall lower concentration (∼25%, p < 0.05) of EVs. At baseline, let-7a, let-7b and let-7e were downregulated in individuals with CP compared to TD (p < 0.05), while miR-100 expression was higher, and miR-877 and miR-4433 lower in CP compared to TD after exercise (p < 0.05). Interestingly, miR-486 was upregulated ∼2-fold in the EVs of CP vs. TD both at baseline and after exercise. We then performed an in silico analysis of miR-486 targets and identified the satellite cell stemness factor Pax7 as a target of miR-486. C2C12 myoblasts were cultured with a miR-486 mimetic and RNA-sequencing was performed. Gene enrichment analysis revealed that several genes involved in sarcomerogenesis and extracellular matrix (ECM) were downregulated. Our data suggest that circulating miR-486 transported by EVs is elevated in individuals with CP and that miR-486 alters the transcriptome of myoblasts affecting both ECM- and sarcomerogenesis-related genes, providing a link to the skeletal muscle alterations observed in individuals with CP In this study, the properties of circulating extracellular vesicles (EVs) were examined in cerebral palsy (CP) and typically developed (TD) individuals at rest and after aerobic exercise, focusing on the size, concentration, and microRNA cargo of EVs. Nine adult individuals with CP performed a single exercise bout consisting of 45 min of Frame Running, and TD participants completed either 45 min of cycling (n = 10; TD EX) or were enrolled as controls with no exercise (n = 10; TD CON). Blood was drawn before and 30 min after exercise and analyzed for EV concentration, size, and microRNA content. The size of EVs was similar in CP vs. TD, and exercise had no effect. Individuals with CP had an overall lower concentration (∼25%, p < 0.05) of EVs. At baseline, let-7a, let-7b and let-7e were downregulated in individuals with CP compared to TD (p < 0.05), while miR-100 expression was higher, and miR-877 and miR-4433 lower in CP compared to TD after exercise (p < 0.05). Interestingly, miR-486 was upregulated ∼2-fold in the EVs of CP vs. TD both at baseline and after exercise. We then performed an in silico analysis of miR-486 targets and identified the satellite cell stemness factor Pax7 as a target of miR-486. C2C12 myoblasts were cultured with a miR-486 mimetic and RNA-sequencing was performed. Gene enrichment analysis revealed that several genes involved in sarcomerogenesis and extracellular matrix (ECM) were downregulated. Our data suggest that circulating miR-486 transported by EVs is elevated in individuals with CP and that miR-486 alters the transcriptome of myoblasts affecting both ECM- and sarcomerogenesis-related genes, providing a link to the skeletal muscle alterations observed in individuals with CP.
- Published
- 2022
3. Epigenetic Marks at the Ribosomal DNA Promoter in Skeletal Muscle Are Negatively Associated With Degree of Impairment in Cerebral Palsy
- Author
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von Walden, Ferdinand, Fernandez-Gonzalo, Rodrigo, Pingel, Jessica, McCarthy, John, Stål, Per, and Pontén, Eva
- Subjects
cerebral palsy ,DNA methylation ,epigenetics ,Pediatrics, Perinatology and Child Health ,ribosome biogenesis ,Pediatrik ,Brief Research Report ,skeletal muscle ,Pediatrics - Abstract
Introduction: Cerebral palsy (CP) is the most common motor impairment in children. Skeletal muscles in individuals with CP are typically weak, thin, and stiff. Whether epigenetic changes at the ribosomal DNA (rDNA) promoter are involved in this dysregulation remains unknown. Methods: Skeletal muscle samples were collected from 19 children with CP and 10 typically developed (TD) control children. Methylation of the rDNA promoter was analyzed using the Agena Epityper Mass array and gene expression by qRT-PCR. Results: Biceps brachii muscle ribosome biogenesis was suppressed in CP as compared to TD. Average methylation of the rDNA promoter was not different between CP and TD but negatively correlated to elbow flexor contracture in the CP group. Discussions: We observed a negative correlation between rDNA promoter methylation and degree of muscle contracture in the CP group. Children with CP with more severe motor impairment had less methylation of the rDNA promoter compared to less affected children. This finding suggests the importance of neural input and voluntary muscle movements for promoter methylation to occur in the biceps muscle.
- Published
- 2020
4. Reduced mitochondrial DNA and OXPHOS protein content in skeletal muscle of children with cerebral palsy.
- Author
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von Walden, Ferdinand, Vechetti, Ivan J, Englund, Davis, Figueiredo, Vandré C, Fernandez‐Gonzalo, Rodrigo, Murach, Kevin, Pingel, Jessica, Mccarthy, John J, Stål, Per, and Pontén, Eva
- Subjects
CHILDREN with cerebral palsy ,TYPE 2 diabetes ,MITOCHONDRIAL DNA ,SKELETAL muscle ,SPECIFIC language impairment in children ,PGC-1 protein ,AEROBIC capacity - Abstract
Skeletal muscle in individuals with CP also contains lower amounts of mtDNA, potentially indicating fewer mitochondria in CP skeletal muscle compared with typically developing muscle. We compared skeletal muscle samples from children with cerebral palsy (CP) and typically developing children and observed evidence of reduced mtDNA and OXPHOS protein content in CP skeletal muscle, indicating reduced mitochondrial abundance. Cerebral palsy (CP) muscle contains fewer energy-generating organelles than typically developing muscle. [Extracted from the article]
- Published
- 2021
- Full Text
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5. Muscle contractures in patients with cerebral palsy and acquired brain injury are associated with extracellular matrix expansion, pro-inflammatory gene expression, and reduced rRNA synthesis.
- Author
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Von Walden, Ferdinand, Gantelius, Stefan, Liu, Chang, Borgström, Hanna, Björk, Lars, Gremark, Ola, Stål, Per, Nader, Gustavo A., and PontéN, Eva
- Abstract
Introduction: Children with cerebral palsy (CP) and acquired brain injury (ABI) commonly develop muscle contractures with advancing age. An underlying growth defect contributing to skeletal muscle contracture formation in CP/ABI has been suggested.Methods: The biceps muscles of children and adolescents with CP/ABI (n = 20) and typically developing controls (n = 10) were investigated. We used immunohistochemistry, quantitative real-time polymerase chain reaction, and Western blotting to assess gene expression relevant to growth and size homeostasis.Results: Classical pro-inflammatory cytokines and genes involved in extracellular matrix (ECM) production were elevated in skeletal muscle of children with CP/ABI. Intramuscular collagen content was increased and satellite cell number decreased and this was associated with reduced levels of RNA polymerase I transcription factors, 45s pre-rRNA and 28S rRNA.Discussion: The present study provides novel data suggesting a role for pro-inflammatory cytokines and reduced ribosomal production in the development/maintenance of muscle contractures, possibly underlying stunted growth and perimysial ECM expansion. Muscle Nerve 58: 277-285, 2018. [ABSTRACT FROM AUTHOR]- Published
- 2018
- Full Text
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6. Forearm Flexor Muscles in Children with Cerebral Palsy Are Weak, Thin and Stiff.
- Author
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von Walden, Ferdinand, Jalaleddini, Kian, Evertsson, Björn, Friberg, Johanna, Valero-Cuevas, Francisco J., and Pontén, Eva
- Subjects
CEREBRAL palsy ,SKELETAL muscle ,BIOMECHANICS ,WRIST ,BRAIN damage - Abstract
Children with cerebral palsy (CP) often develop reduced passive range of motion with age. The determining factor underlying this process is believed to be progressive development of contracture in skeletal muscle that likely changes the biomechanics of the joints. Consequently, to identify the underlying mechanisms, we modeled the mechanical characteristics of the forearm flexors acting across the wrist joint. We investigated skeletal muscle strength (Grippit®) and passive stiffness and viscosity of the forearm flexors in 15 typically developing (TD) children (10 boys/5 girls, mean age 12 years, range 8-18 yrs) and nine children with CP Nine children (6 boys/3 girls, mean age 11 ± 3 years (yrs), range 7-15 yrs) using the NeuroFlexor® apparatus. The muscle stiffness we estimate and report is the instantaneous mechanical response of the tissue that is independent of reflex activity. Furthermore, we assessed cross-sectional area of the flexor carpi radialis (FCR) muscle using ultrasound. Age and body weight did not differ significantly between the two groups. Children with CP had a significantly weaker (-65%, p < 0.01) grip and had smaller cross-sectional area (-43%, p < 0.01) of the FCR muscle. Passive stiffness of the forearm muscles in children with CP was increased 2-fold (p < 0.05) whereas viscosity did not differ significantly between CP and TD children. FCR cross-sectional area correlated to age (R² = 0.58, p < 0.01), body weight (R² = 0.92, p < 0.0001) and grip strength (R² = 0.82, p < 0.0001) in TD children but only to grip strength (R² = 0.60, p < 0.05) in children with CP. We conclude that children with CP have weaker, thinner, and stiffer forearm flexors as compared to typically developing children. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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7. Immobilization of the rabbit tibialis anterior muscle in a lengthened position causes addition of sarcomeres in series and extra-cellular matrix proliferation
- Author
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Pontén, Eva and Fridén, Jan
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MUSCLES , *CELL proliferation , *NITRIC acid , *LABORATORY rabbits - Abstract
Abstract: Rabbits were immobilized for 3 weeks with the ankle in plantar flexion, midrange position or dorsal extension (n=15). The left leg was used as control. Sarcomere lengths were measured by laser diffraction in vivo in the tibialis anterior (TA) muscle. Legs immobilized in the midrange position showed coherent diffraction patterns through the range of motion, but in those immobilized with TA in the stretched position no diffraction patterns in vivo could be obtained. Morphological analyses revealed increased fibrosis and occurrence of whorled fibers in these muscles. On 15 more likewise immobilized rabbits, a technique of measuring sarcomere lengths in vitro by first digesting the collagen in nitric acid was developed. These in vitro measurements showed shorter sarcomeres in the muscles immobilized in a lengthened position compared to the control, indicating an addition of sarcomeres in series. [Copyright &y& Elsevier]
- Published
- 2008
- Full Text
- View/download PDF
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