Endurance exercise has a negative impact on the onset of SOD1-G93A ALS in female mice and affects the entire skeletal muscle-motor neuron axis
Background:Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disease characterized by the degeneration of motor neurons that leads to muscle wasting and atrophy. Epidemiological and experimental evidence suggests a causal relationship between ALS and physical activity (PA). However, the i...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2024.1360099/full |
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| author | Silvia Scaricamazza Valentina Nesci Valentina Nesci Illari Salvatori Illari Salvatori Gianmarco Fenili Gianmarco Fenili Marco Rosina Marco Rosina Michela Gloriani Michela Gloriani Maria Paola Paronetto Maria Paola Paronetto Luca Madaro Luca Madaro Alberto Ferri Alberto Ferri Cristiana Valle Cristiana Valle |
| author_facet | Silvia Scaricamazza Valentina Nesci Valentina Nesci Illari Salvatori Illari Salvatori Gianmarco Fenili Gianmarco Fenili Marco Rosina Marco Rosina Michela Gloriani Michela Gloriani Maria Paola Paronetto Maria Paola Paronetto Luca Madaro Luca Madaro Alberto Ferri Alberto Ferri Cristiana Valle Cristiana Valle |
| author_sort | Silvia Scaricamazza |
| collection | DOAJ |
| description | Background:Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disease characterized by the degeneration of motor neurons that leads to muscle wasting and atrophy. Epidemiological and experimental evidence suggests a causal relationship between ALS and physical activity (PA). However, the impact of PA on motor neuron loss and sarcopenia is still debated, probably because of the heterogeneity and intensities of the proposed exercises. With this study, we aimed to clarify the effect of intense endurance exercise on the onset and progression of ALS in the SOD1-G93A mouse model.Methods:We randomly selected four groups of twelve 35-day-old female mice. SOD1-G93A and WT mice underwent intense endurance training on a motorized treadmill for 8 weeks, 5 days a week. During the training, we measured muscle strength, weight, and motor skills and compared them with the corresponding sedentary groups to define the disease onset. At the end of the eighth week, we analyzed the skeletal muscle-motor neuron axis by histological and molecular techniques.Results:Intense endurance exercise anticipates the onset of the disease by 1 week (age of the onset: trained SOD1-G93A = 63.17 ± 2.25 days old; sedentary SOD1-G93A = 70.75 ± 2.45 days old). In SOD1-G93A mice, intense endurance exercise hastens the muscular switch to a more oxidative phenotype and worsens the denervation process by dismantling neuromuscular junctions in the tibialis anterior, enhancing the Wallerian degeneration in the sciatic nerve, and promoting motor neuron loss in the spinal cord. The training exacerbates neuroinflammation, causing immune cell infiltration in the sciatic nerve and a faster activation of astrocytes and microglia in the spinal cord.Conclusion:Intense endurance exercise, acting on skeletal muscles, worsens the pathological hallmarks of ALS, such as denervation and neuroinflammation, brings the onset forward, and accelerates the progression of the disease. Our findings show the potentiality of skeletal muscle as a target for both prognostic and therapeutic strategies; the preservation of skeletal muscle health by specific intervention could counteract the dying-back process and protect motor neurons from death. The physiological characteristics and accessibility of skeletal muscle further enhance its appeal as a therapeutic target. |
| first_indexed | 2024-04-24T19:47:08Z |
| format | Article |
| id | doaj.art-361c58a3020f4604974940ceb25ca7e7 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-24T19:47:08Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-361c58a3020f4604974940ceb25ca7e72024-03-25T04:50:46ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122024-03-011510.3389/fphar.2024.13600991360099Endurance exercise has a negative impact on the onset of SOD1-G93A ALS in female mice and affects the entire skeletal muscle-motor neuron axisSilvia Scaricamazza0Valentina Nesci1Valentina Nesci2Illari Salvatori3Illari Salvatori4Gianmarco Fenili5Gianmarco Fenili6Marco Rosina7Marco Rosina8Michela Gloriani9Michela Gloriani10Maria Paola Paronetto11Maria Paola Paronetto12Luca Madaro13Luca Madaro14Alberto Ferri15Alberto Ferri16Cristiana Valle17Cristiana Valle18IRCCS Fondazione Santa Lucia, Rome, ItalyIRCCS Fondazione Santa Lucia, Rome, ItalyDepartment of Systems Medicine, University of Roma “Tor Vergata”, Rome, ItalyIRCCS Fondazione Santa Lucia, Rome, ItalyDepartment of Experimental Medicine, University of Roma “La Sapienza”, Rome, ItalyIRCCS Fondazione Santa Lucia, Rome, ItalyDepartment of Movement, Human and Health Sciences, University of Rome “Foro Italico”, Rome, ItalyIRCCS Fondazione Santa Lucia, Rome, ItalyNeurology Unit, PTV Foundation Tor Vergata University Hospital, Rome, ItalyDepartment of Anatomy, Histology, Forensic Medicine and Orthopedics, University of Roma “La Sapienza”, Rome, ItalyLaboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Rome, ItalyIRCCS Fondazione Santa Lucia, Rome, ItalyDepartment of Movement, Human and Health Sciences, University of Rome “Foro Italico”, Rome, ItalyDepartment of Anatomy, Histology, Forensic Medicine and Orthopedics, University of Roma “La Sapienza”, Rome, ItalyLaboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Rome, ItalyIRCCS Fondazione Santa Lucia, Rome, ItalyNational Research Council (CNR), Institute of Translational Pharmacology (IFT), Rome, ItalyIRCCS Fondazione Santa Lucia, Rome, ItalyNational Research Council (CNR), Institute of Translational Pharmacology (IFT), Rome, ItalyBackground:Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disease characterized by the degeneration of motor neurons that leads to muscle wasting and atrophy. Epidemiological and experimental evidence suggests a causal relationship between ALS and physical activity (PA). However, the impact of PA on motor neuron loss and sarcopenia is still debated, probably because of the heterogeneity and intensities of the proposed exercises. With this study, we aimed to clarify the effect of intense endurance exercise on the onset and progression of ALS in the SOD1-G93A mouse model.Methods:We randomly selected four groups of twelve 35-day-old female mice. SOD1-G93A and WT mice underwent intense endurance training on a motorized treadmill for 8 weeks, 5 days a week. During the training, we measured muscle strength, weight, and motor skills and compared them with the corresponding sedentary groups to define the disease onset. At the end of the eighth week, we analyzed the skeletal muscle-motor neuron axis by histological and molecular techniques.Results:Intense endurance exercise anticipates the onset of the disease by 1 week (age of the onset: trained SOD1-G93A = 63.17 ± 2.25 days old; sedentary SOD1-G93A = 70.75 ± 2.45 days old). In SOD1-G93A mice, intense endurance exercise hastens the muscular switch to a more oxidative phenotype and worsens the denervation process by dismantling neuromuscular junctions in the tibialis anterior, enhancing the Wallerian degeneration in the sciatic nerve, and promoting motor neuron loss in the spinal cord. The training exacerbates neuroinflammation, causing immune cell infiltration in the sciatic nerve and a faster activation of astrocytes and microglia in the spinal cord.Conclusion:Intense endurance exercise, acting on skeletal muscles, worsens the pathological hallmarks of ALS, such as denervation and neuroinflammation, brings the onset forward, and accelerates the progression of the disease. Our findings show the potentiality of skeletal muscle as a target for both prognostic and therapeutic strategies; the preservation of skeletal muscle health by specific intervention could counteract the dying-back process and protect motor neurons from death. The physiological characteristics and accessibility of skeletal muscle further enhance its appeal as a therapeutic target.https://www.frontiersin.org/articles/10.3389/fphar.2024.1360099/fullamyotrophic lateral sclerosisphysical activityendurance exerciseneurodegenerationneuroinflammationSOD1-G93A mice |
| spellingShingle | Silvia Scaricamazza Valentina Nesci Valentina Nesci Illari Salvatori Illari Salvatori Gianmarco Fenili Gianmarco Fenili Marco Rosina Marco Rosina Michela Gloriani Michela Gloriani Maria Paola Paronetto Maria Paola Paronetto Luca Madaro Luca Madaro Alberto Ferri Alberto Ferri Cristiana Valle Cristiana Valle Endurance exercise has a negative impact on the onset of SOD1-G93A ALS in female mice and affects the entire skeletal muscle-motor neuron axis Frontiers in Pharmacology amyotrophic lateral sclerosis physical activity endurance exercise neurodegeneration neuroinflammation SOD1-G93A mice |
| title | Endurance exercise has a negative impact on the onset of SOD1-G93A ALS in female mice and affects the entire skeletal muscle-motor neuron axis |
| title_full | Endurance exercise has a negative impact on the onset of SOD1-G93A ALS in female mice and affects the entire skeletal muscle-motor neuron axis |
| title_fullStr | Endurance exercise has a negative impact on the onset of SOD1-G93A ALS in female mice and affects the entire skeletal muscle-motor neuron axis |
| title_full_unstemmed | Endurance exercise has a negative impact on the onset of SOD1-G93A ALS in female mice and affects the entire skeletal muscle-motor neuron axis |
| title_short | Endurance exercise has a negative impact on the onset of SOD1-G93A ALS in female mice and affects the entire skeletal muscle-motor neuron axis |
| title_sort | endurance exercise has a negative impact on the onset of sod1 g93a als in female mice and affects the entire skeletal muscle motor neuron axis |
| topic | amyotrophic lateral sclerosis physical activity endurance exercise neurodegeneration neuroinflammation SOD1-G93A mice |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1360099/full |
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