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5. Circulating immune cell populations at rest and in response to acute endurance exercise in young adults with cerebral palsy.

Author

Kruse, Annika, Imery, Ian, Corell, Linnéa, Hjalmarsson, Emma, Fernandez‐Gonzalo, Rodrigo, Von Walden, Ferdinand, and Reitzner, Stefan M.

Subjects
YOUNG adults, CELL populations, CEREBRAL palsy, RATE of perceived exertion, IMMUNITY
Abstract

Aim: The aim of this observational study was to determine the immune status and function in young adults with cerebral palsy (CP) in comparison to typically developing individuals. Method: Blood samples from 12 individuals with CP (five males, seven females; mean age: 25 years 1 month (5 years 9 months); age range: 19–38 years) and 17 typically developing individuals (eight males, nine females; mean age: 31 years 4 months (6 years 2 months); age range: 20–40 years) were collected before, immediately after, and 1 hour after 45 minutes of frame running or running respectively. Independent t‐tests were used to compare heart rate, level of exertion, and baseline cell proportions between groups. Mixed model analysis of variance was utilized to investigate immune cell responses to exercise across groups. Results: Baseline levels of gamma delta (TCRγδ+) T‐cells were significantly higher (absolute percentage: +2.65, p = 0.028) in the individuals with CP. Several cell populations showed similar significant changes after exercise in both CP and typically developing groups. Cytotoxic (CD8+) T‐cells were only significantly elevated immediately after exercise in the typically developing participants (p < 0.01). Individuals with CP exhibited significantly lower heart rates (−11.1%, p < 0.01), despite similar ratings of perceived exertion. Interpretation: Elevated baseline TCRγδ+ T‐cells may indicate low‐grade inflammation in adults with CP. Although most of the cell populations showed typical responses to endurance exercise, the absence of response in CD8+ T‐cells in individuals with CP may indicate the need for higher intensity during exercise. What this paper adds: TCRγδ+ T‐cell baseline levels are elevated in adults with cerebral palsy (CP).The CD8+ T‐cell response to exercise was blunted in adults with CP.Exercise intensity is decisive for CD8+ T‐cell responses in individuals with CP. [ABSTRACT FROM AUTHOR]

Published
2024
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19. Extracellular vesicle characteristics and microRNA content in cerebral palsy and typically developed individuals at rest and in response to aerobic exercise

Author

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

21. Acute endurance exercise stimulates circulating levels of mitochondrial-derived peptides in humans

Author

von Walden, Ferdinand, primary, Fernandez-Gonzalo, Rodrigo, additional, Norrbom, Jessica, additional, Emanuelsson, Eric B., additional, Figueiredo, Vandré C., additional, Gidlund, Eva-Karin, additional, Norrbrand, Lena, additional, Liu, Chang, additional, Sandström, Philip, additional, Hansson, Björn, additional, Wan, Junxiang, additional, Cohen, Pinchas, additional, and Alkner, Björn, additional

Published
2021
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25. Genetic and epigenetic regulation of skeletal muscle ribosome biogenesis with exercise

Author

Figueiredo, Vandré C., primary, Wen, Yuan, additional, Alkner, Björn, additional, Fernandez‐Gonzalo, Rodrigo, additional, Norrbom, Jessica, additional, Vechetti, Ivan J., additional, Valentino, Taylor, additional, Mobley, C. Brooks, additional, Zentner, Gabriel E., additional, Peterson, Charlotte A., additional, McCarthy, John J., additional, Murach, Kevin A., additional, and von Walden, Ferdinand, additional

Published
2021
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27. Epigenetic Marks at the Ribosomal DNA Promoter in Skeletal Muscle Are Negatively Associated With Degree of Impairment in Cerebral Palsy

Author

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

28. Additional file 2 of RaceRunning training improves stamina and promotes skeletal muscle hypertrophy in young individuals with cerebral palsy

Author

Hjalmarsson, Emma, Fernandez-Gonzalo, Rodrigo, Lidbeck, Cecilia, Palmcrantz, Alexandra, Jia, Angel, Kvist, Ola, Pontén, Eva, and Walden, Ferdinand Von

Abstract

Additional file 2: Table S1. Distribution of spasticity in the lower limb muscles assessed with the modified Ashworth scale and graded as 0, 1, +1, 2, 3, or 4, where 0 indicates no increase in muscle tone and 4 indicates marked increase in muscle tone, before and after a training period with RaceRunning (p-level 0.05).

Published
2020
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33. Skeletal muscle signaling responses to resistance exercise of the elbow extensors are not compromised by a preceding bout of aerobic exercise

Author

Hansson, Björn, primary, Olsen, Luke A., additional, Nicoll, Justin X., additional, von Walden, Ferdinand, additional, Melin, Michael, additional, Strömberg, Anna, additional, Rullman, Eric, additional, Gustafsson, Thomas, additional, Fry, Andrew C., additional, Fernandez-Gonzalo, Rodrigo, additional, and Lundberg, Tommy R., additional

Published
2019
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