Physical Exercise and Mitochondrial Disease: Insights From a Mouse Model
Purpose: Mitochondrial diseases (MD) are among the most prevalent neuromuscular disorders. Unfortunately, no curative treatment is yet available. This study analyzed the effects of exercise training in an animal model of respiratory chain complex I deficiency, the Harlequin (Hq) mouse, which replica...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-07-01
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| Series: | Frontiers in Neurology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fneur.2019.00790/full |
| _version_ | 1819000537402572800 |
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| author | Carmen Fiuza-Luces Pedro L. Valenzuela Sara Laine-Menéndez Miguel Fernández-de la Torre Verónica Bermejo-Gómez Laura Rufián-Vázquez Joaquín Arenas Joaquín Arenas Miguel A. Martín Miguel A. Martín Alejandro Lucia Alejandro Lucia María Morán María Morán |
| author_facet | Carmen Fiuza-Luces Pedro L. Valenzuela Sara Laine-Menéndez Miguel Fernández-de la Torre Verónica Bermejo-Gómez Laura Rufián-Vázquez Joaquín Arenas Joaquín Arenas Miguel A. Martín Miguel A. Martín Alejandro Lucia Alejandro Lucia María Morán María Morán |
| author_sort | Carmen Fiuza-Luces |
| collection | DOAJ |
| description | Purpose: Mitochondrial diseases (MD) are among the most prevalent neuromuscular disorders. Unfortunately, no curative treatment is yet available. This study analyzed the effects of exercise training in an animal model of respiratory chain complex I deficiency, the Harlequin (Hq) mouse, which replicates the clinical features of this condition.Methods: Male heterozygous Harlequin (Hq/Y) mice were assigned to an “exercise” (n = 10) or a “sedentary” control group (n = 11), with the former being submitted to an 8 week combined exercise training intervention (aerobic + resistance training performed five times/week). Aerobic fitness, grip strength, and balance were assessed at the beginning and at the end of the intervention period in all the Hq mice. Muscle biochemical analyses (with results expressed as percentage of reference data from age/sex-matched sedentary wild-type mice [n = 12]) were performed at the end of the aforementioned period for the assessment of major molecular signaling pathways involved in muscle anabolism (mTOR activation) and mitochondrial biogenesis (proliferator activated receptor gamma co-activator 1α [PGC-1α] levels), and enzyme activity and levels of respiratory chain complexes, and antioxidant enzyme levels.Results: Exercise training resulted in significant improvements in aerobic fitness (−33 ± 13 m and 83 ± 43 m for the difference post- vs. pre-intervention in total distance covered in the treadmill tests in control and exercise group, respectively, p = 0.014) and muscle strength (2 ± 4 g vs. 17 ± 6 g for the difference post vs. pre-intervention, p = 0.037) compared to the control group. Higher levels of ribosomal protein S6 kinase beta-1 phosphorylated at threonine 389 (156 ± 30% vs. 249 ± 30%, p = 0.028) and PGC-1α (82 ± 7% vs. 126 ± 19% p = 0.032) were observed in the exercise-trained mice compared with the control group. A higher activity of respiratory chain complexes I (75 ± 4% vs. 95 ± 6%, p = 0.019), III (79 ± 5% vs. 97 ± 4%, p = 0.031), and V (77 ± 9% vs. 105 ± 9%, p = 0.024) was also found with exercise training. Exercised mice presented with lower catalase levels (204 ± 22% vs. 141 ± 23%, p = 0.036).Conclusion: In a mouse model of MD, a training intervention combining aerobic and resistance exercise increased aerobic fitness and muscle strength, and mild improvements were found for activated signaling pathways involved in muscle mitochondrial biogenesis and anabolism, OXPHOS complex activity, and redox status in muscle tissue. |
| first_indexed | 2024-12-20T22:34:54Z |
| format | Article |
| id | doaj.art-6bcc5609ea8842ea82ab1527796f613b |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-12-20T22:34:54Z |
| publishDate | 2019-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-6bcc5609ea8842ea82ab1527796f613b2022-12-21T19:24:38ZengFrontiers Media S.A.Frontiers in Neurology1664-22952019-07-011010.3389/fneur.2019.00790462638Physical Exercise and Mitochondrial Disease: Insights From a Mouse ModelCarmen Fiuza-Luces0Pedro L. Valenzuela1Sara Laine-Menéndez2Miguel Fernández-de la Torre3Verónica Bermejo-Gómez4Laura Rufián-Vázquez5Joaquín Arenas6Joaquín Arenas7Miguel A. Martín8Miguel A. Martín9Alejandro Lucia10Alejandro Lucia11María Morán12María Morán13Mitochondrial and Neuromuscular Diseases Laboratory, Research Institute of Hospital 12 de Octubre (i+12), Madrid, SpainPhysiology Unit, Systems Biology Department, University of Alcalá, Madrid, SpainMitochondrial and Neuromuscular Diseases Laboratory, Research Institute of Hospital 12 de Octubre (i+12), Madrid, SpainMitochondrial and Neuromuscular Diseases Laboratory, Research Institute of Hospital 12 de Octubre (i+12), Madrid, SpainMitochondrial and Neuromuscular Diseases Laboratory, Research Institute of Hospital 12 de Octubre (i+12), Madrid, SpainMitochondrial and Neuromuscular Diseases Laboratory, Research Institute of Hospital 12 de Octubre (i+12), Madrid, SpainMitochondrial and Neuromuscular Diseases Laboratory, Research Institute of Hospital 12 de Octubre (i+12), Madrid, SpainSpanish Network for Biomedical Research in Rare Diseases (CIBERER), Madrid, SpainMitochondrial and Neuromuscular Diseases Laboratory, Research Institute of Hospital 12 de Octubre (i+12), Madrid, SpainSpanish Network for Biomedical Research in Rare Diseases (CIBERER), Madrid, SpainFaculty of Sports Sciences, European University of Madrid, Madrid, SpainSpanish Network for Biomedical Research in Fragility and Healthy Aging (CIBERFES), Madrid, SpainMitochondrial and Neuromuscular Diseases Laboratory, Research Institute of Hospital 12 de Octubre (i+12), Madrid, SpainSpanish Network for Biomedical Research in Rare Diseases (CIBERER), Madrid, SpainPurpose: Mitochondrial diseases (MD) are among the most prevalent neuromuscular disorders. Unfortunately, no curative treatment is yet available. This study analyzed the effects of exercise training in an animal model of respiratory chain complex I deficiency, the Harlequin (Hq) mouse, which replicates the clinical features of this condition.Methods: Male heterozygous Harlequin (Hq/Y) mice were assigned to an “exercise” (n = 10) or a “sedentary” control group (n = 11), with the former being submitted to an 8 week combined exercise training intervention (aerobic + resistance training performed five times/week). Aerobic fitness, grip strength, and balance were assessed at the beginning and at the end of the intervention period in all the Hq mice. Muscle biochemical analyses (with results expressed as percentage of reference data from age/sex-matched sedentary wild-type mice [n = 12]) were performed at the end of the aforementioned period for the assessment of major molecular signaling pathways involved in muscle anabolism (mTOR activation) and mitochondrial biogenesis (proliferator activated receptor gamma co-activator 1α [PGC-1α] levels), and enzyme activity and levels of respiratory chain complexes, and antioxidant enzyme levels.Results: Exercise training resulted in significant improvements in aerobic fitness (−33 ± 13 m and 83 ± 43 m for the difference post- vs. pre-intervention in total distance covered in the treadmill tests in control and exercise group, respectively, p = 0.014) and muscle strength (2 ± 4 g vs. 17 ± 6 g for the difference post vs. pre-intervention, p = 0.037) compared to the control group. Higher levels of ribosomal protein S6 kinase beta-1 phosphorylated at threonine 389 (156 ± 30% vs. 249 ± 30%, p = 0.028) and PGC-1α (82 ± 7% vs. 126 ± 19% p = 0.032) were observed in the exercise-trained mice compared with the control group. A higher activity of respiratory chain complexes I (75 ± 4% vs. 95 ± 6%, p = 0.019), III (79 ± 5% vs. 97 ± 4%, p = 0.031), and V (77 ± 9% vs. 105 ± 9%, p = 0.024) was also found with exercise training. Exercised mice presented with lower catalase levels (204 ± 22% vs. 141 ± 23%, p = 0.036).Conclusion: In a mouse model of MD, a training intervention combining aerobic and resistance exercise increased aerobic fitness and muscle strength, and mild improvements were found for activated signaling pathways involved in muscle mitochondrial biogenesis and anabolism, OXPHOS complex activity, and redox status in muscle tissue.https://www.frontiersin.org/article/10.3389/fneur.2019.00790/fullrare diseasesmitochondrial diseasesOXPHOSharlequin mutant mouseresistance trainingAIF deficiency |
| spellingShingle | Carmen Fiuza-Luces Pedro L. Valenzuela Sara Laine-Menéndez Miguel Fernández-de la Torre Verónica Bermejo-Gómez Laura Rufián-Vázquez Joaquín Arenas Joaquín Arenas Miguel A. Martín Miguel A. Martín Alejandro Lucia Alejandro Lucia María Morán María Morán Physical Exercise and Mitochondrial Disease: Insights From a Mouse Model Frontiers in Neurology rare diseases mitochondrial diseases OXPHOS harlequin mutant mouse resistance training AIF deficiency |
| title | Physical Exercise and Mitochondrial Disease: Insights From a Mouse Model |
| title_full | Physical Exercise and Mitochondrial Disease: Insights From a Mouse Model |
| title_fullStr | Physical Exercise and Mitochondrial Disease: Insights From a Mouse Model |
| title_full_unstemmed | Physical Exercise and Mitochondrial Disease: Insights From a Mouse Model |
| title_short | Physical Exercise and Mitochondrial Disease: Insights From a Mouse Model |
| title_sort | physical exercise and mitochondrial disease insights from a mouse model |
| topic | rare diseases mitochondrial diseases OXPHOS harlequin mutant mouse resistance training AIF deficiency |
| url | https://www.frontiersin.org/article/10.3389/fneur.2019.00790/full |
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