Rehabilitative Impact of Exercise Training on Human Skeletal Muscle Transcriptional Programs in Parkinson’s Disease
Parkinson’s disease (PD) is the most common motor neurodegenerative disease, and neuromuscular function deficits associated with PD contribute to disability. Targeting these symptoms, our laboratory has previously evaluated 16-week high-intensity resistance exercise as rehabilitative training (RT) i...
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Frontiers Media S.A.
2020-06-01
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Online Access: | https://www.frontiersin.org/article/10.3389/fphys.2020.00653/full |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kaleen M. Lavin Kaleen M. Lavin Yongchao Ge Yongchao Ge Stuart C. Sealfon Stuart C. Sealfon Venugopalan D. Nair Venugopalan D. Nair Katarzyna Wilk Katarzyna Wilk Jeremy S. McAdam Jeremy S. McAdam Samuel T. Windham Samuel T. Windham Preeti Lakshman Kumar Preeti Lakshman Kumar Merry-Lynn N. McDonald Merry-Lynn N. McDonald Marcas M. Bamman Marcas M. Bamman Marcas M. Bamman Marcas M. Bamman Marcas M. Bamman |
spellingShingle |
Kaleen M. Lavin Kaleen M. Lavin Yongchao Ge Yongchao Ge Stuart C. Sealfon Stuart C. Sealfon Venugopalan D. Nair Venugopalan D. Nair Katarzyna Wilk Katarzyna Wilk Jeremy S. McAdam Jeremy S. McAdam Samuel T. Windham Samuel T. Windham Preeti Lakshman Kumar Preeti Lakshman Kumar Merry-Lynn N. McDonald Merry-Lynn N. McDonald Marcas M. Bamman Marcas M. Bamman Marcas M. Bamman Marcas M. Bamman Marcas M. Bamman Rehabilitative Impact of Exercise Training on Human Skeletal Muscle Transcriptional Programs in Parkinson’s Disease Frontiers in Physiology Parkinson’s disease high-intensity exercise training transcriptome neuromuscular motor unit |
author_facet |
Kaleen M. Lavin Kaleen M. Lavin Yongchao Ge Yongchao Ge Stuart C. Sealfon Stuart C. Sealfon Venugopalan D. Nair Venugopalan D. Nair Katarzyna Wilk Katarzyna Wilk Jeremy S. McAdam Jeremy S. McAdam Samuel T. Windham Samuel T. Windham Preeti Lakshman Kumar Preeti Lakshman Kumar Merry-Lynn N. McDonald Merry-Lynn N. McDonald Marcas M. Bamman Marcas M. Bamman Marcas M. Bamman Marcas M. Bamman Marcas M. Bamman |
author_sort |
Kaleen M. Lavin |
title |
Rehabilitative Impact of Exercise Training on Human Skeletal Muscle Transcriptional Programs in Parkinson’s Disease |
title_short |
Rehabilitative Impact of Exercise Training on Human Skeletal Muscle Transcriptional Programs in Parkinson’s Disease |
title_full |
Rehabilitative Impact of Exercise Training on Human Skeletal Muscle Transcriptional Programs in Parkinson’s Disease |
title_fullStr |
Rehabilitative Impact of Exercise Training on Human Skeletal Muscle Transcriptional Programs in Parkinson’s Disease |
title_full_unstemmed |
Rehabilitative Impact of Exercise Training on Human Skeletal Muscle Transcriptional Programs in Parkinson’s Disease |
title_sort |
rehabilitative impact of exercise training on human skeletal muscle transcriptional programs in parkinson’s disease |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Physiology |
issn |
1664-042X |
publishDate |
2020-06-01 |
description |
Parkinson’s disease (PD) is the most common motor neurodegenerative disease, and neuromuscular function deficits associated with PD contribute to disability. Targeting these symptoms, our laboratory has previously evaluated 16-week high-intensity resistance exercise as rehabilitative training (RT) in individuals with PD. We reported significant improvements in muscle mass, neuromuscular function (strength, power, and motor unit activation), indices of neuromuscular junction integrity, total and motor scores on the unified Parkinson’s disease rating scale (UPDRS), and total and sub-scores on the 39-item PD Quality of Life Questionnaire (PDQ-39), supporting the use of RT to reverse symptoms. Our objective was to identify transcriptional networks that may contribute to RT-induced neuromuscular remodeling in PD. We generated transcriptome-wide skeletal muscle RNA-sequencing in 5 participants with PD [4M/1F, 67 ± 2 years, Hoehn and Yahr stages 2 (n = 3) and 3 (n = 2)] before and after 16-week high intensity RT to identify transcriptional networks that may in part underpin RT-induced neuromuscular remodeling in PD. Following RT, 304 genes were significantly upregulated, notably related to remodeling and nervous system/muscle development. Additionally, 402 genes, primarily negative regulators of muscle adaptation, were downregulated. We applied the recently developed Pathway-Level Information ExtractoR (PLIER) method to reveal coordinated gene programs (as latent variables, LVs) that differed in skeletal muscle among young (YA) and old (OA) healthy adults and PD (n = 12 per cohort) at baseline and in PD pre- vs. post-RT. Notably, one LV associated with angiogenesis, axon guidance, and muscle remodeling was significantly lower in PD than YA at baseline and was significantly increased by exercise. A different LV annotated to denervation, autophagy, and apoptosis was increased in both PD and OA relative to YA and was also reduced by 16-week RT in PD. Thus, this analysis identified two novel skeletal muscle transcriptional programs that are dysregulated by PD and aging, respectively. Notably, RT has a normalizing effect on both programs in individuals with PD. These results identify potential molecular transducers of the RT-induced improvements in neuromuscular remodeling and motor function that may aid in optimizing exercise rehabilitation strategies for individuals with PD. |
topic |
Parkinson’s disease high-intensity exercise training transcriptome neuromuscular motor unit |
url |
https://www.frontiersin.org/article/10.3389/fphys.2020.00653/full |
work_keys_str_mv |
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doaj-7e10fa3bb8e5477faab9386fb5c195322020-11-25T03:45:49ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2020-06-011110.3389/fphys.2020.00653512516Rehabilitative Impact of Exercise Training on Human Skeletal Muscle Transcriptional Programs in Parkinson’s DiseaseKaleen M. Lavin0Kaleen M. Lavin1Yongchao Ge2Yongchao Ge3Stuart C. Sealfon4Stuart C. Sealfon5Venugopalan D. Nair6Venugopalan D. Nair7Katarzyna Wilk8Katarzyna Wilk9Jeremy S. McAdam10Jeremy S. McAdam11Samuel T. Windham12Samuel T. Windham13Preeti Lakshman Kumar14Preeti Lakshman Kumar15Merry-Lynn N. McDonald16Merry-Lynn N. McDonald17Marcas M. Bamman18Marcas M. Bamman19Marcas M. Bamman20Marcas M. Bamman21Marcas M. Bamman22Department of Cell, Developmental and Integrative Biology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, United StatesUAB Center for Exercise Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesCenter for Advanced Research on Diagnostic Assays, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesCenter for Advanced Research on Diagnostic Assays, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesCenter for Advanced Research on Diagnostic Assays, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesCenter for Advanced Research on Diagnostic Assays, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDepartment of Cell, Developmental and Integrative Biology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, United StatesUAB Center for Exercise Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, United StatesUAB Center for Exercise Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Surgery, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Genetics, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Genetics, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Cell, Developmental and Integrative Biology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, United StatesUAB Center for Exercise Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, United StatesBirmingham/Atlanta VA Geriatric Research, Education, and Clinical Center, Birmingham, AL, United StatesDepartment of Neurology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, United StatesParkinson’s disease (PD) is the most common motor neurodegenerative disease, and neuromuscular function deficits associated with PD contribute to disability. Targeting these symptoms, our laboratory has previously evaluated 16-week high-intensity resistance exercise as rehabilitative training (RT) in individuals with PD. We reported significant improvements in muscle mass, neuromuscular function (strength, power, and motor unit activation), indices of neuromuscular junction integrity, total and motor scores on the unified Parkinson’s disease rating scale (UPDRS), and total and sub-scores on the 39-item PD Quality of Life Questionnaire (PDQ-39), supporting the use of RT to reverse symptoms. Our objective was to identify transcriptional networks that may contribute to RT-induced neuromuscular remodeling in PD. We generated transcriptome-wide skeletal muscle RNA-sequencing in 5 participants with PD [4M/1F, 67 ± 2 years, Hoehn and Yahr stages 2 (n = 3) and 3 (n = 2)] before and after 16-week high intensity RT to identify transcriptional networks that may in part underpin RT-induced neuromuscular remodeling in PD. Following RT, 304 genes were significantly upregulated, notably related to remodeling and nervous system/muscle development. Additionally, 402 genes, primarily negative regulators of muscle adaptation, were downregulated. We applied the recently developed Pathway-Level Information ExtractoR (PLIER) method to reveal coordinated gene programs (as latent variables, LVs) that differed in skeletal muscle among young (YA) and old (OA) healthy adults and PD (n = 12 per cohort) at baseline and in PD pre- vs. post-RT. Notably, one LV associated with angiogenesis, axon guidance, and muscle remodeling was significantly lower in PD than YA at baseline and was significantly increased by exercise. A different LV annotated to denervation, autophagy, and apoptosis was increased in both PD and OA relative to YA and was also reduced by 16-week RT in PD. Thus, this analysis identified two novel skeletal muscle transcriptional programs that are dysregulated by PD and aging, respectively. Notably, RT has a normalizing effect on both programs in individuals with PD. These results identify potential molecular transducers of the RT-induced improvements in neuromuscular remodeling and motor function that may aid in optimizing exercise rehabilitation strategies for individuals with PD.https://www.frontiersin.org/article/10.3389/fphys.2020.00653/fullParkinson’s diseasehigh-intensity exercise trainingtranscriptomeneuromuscularmotor unit |