Functional over-load saves motor units in the SOD1-G93A transgenic mouse model of amyotrophic lateral sclerosis
The fastest, most forceful motor units are lost progressively during asymptomatic disease in the SOD1G93A transgenic mouse model of amyotrophic lateral sclerosis. As the disease progresses the surviving motor units must increase their levels of activity to sustain posture and movement. If activity-d...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2010-02-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996109003076 |
| _version_ | 1818724663583309824 |
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| author | T. Gordon N. Tyreman S. Li C.T. Putman J. Hegedus |
| author_facet | T. Gordon N. Tyreman S. Li C.T. Putman J. Hegedus |
| author_sort | T. Gordon |
| collection | DOAJ |
| description | The fastest, most forceful motor units are lost progressively during asymptomatic disease in the SOD1G93A transgenic mouse model of amyotrophic lateral sclerosis. As the disease progresses the surviving motor units must increase their levels of activity to sustain posture and movement. If activity-dependent conversion of motor units to more fatigue resistant types increased their resilience and hence survival, we hypothesized that an experimental increase in motor unit activity in the hindlimb muscles of the SOD1G93A transgenic mouse should “save” those motor units that are normally lost in the first 90 days of age. To test this hypothesis, we partially denervated hindlimb muscles in SOD1G93A and their corresponding control SOD1WT transgenic mice by avulsion of either L4 or L5 spinal roots at 40 days of age. Whole muscle and single motor unit isometric twitch forces were recorded and the numbers intact motor units in fast-twitch tibialis anterior, medial gastrocnemius, extensor digitorum longus muscles and the slow-twitch soleus muscle were calculated at 90 days of age. We found that the rapid age-dependent decline in numbers of functional motor units in fast-twitch muscles of the SOD1G93A transgenic mice was dramatically reduced by the functional hyperactivity in the partially denervated muscles and, that these muscles comprised a significantly higher component of type IIA and type IID/X fibers than those muscles that were innervated by nerves in intact spinal roots. We conclude that the vulnerable motor units are saved by increasing their neuromuscular activity and consequently, converting them to slower, less forceful, fatigue resistant motor units. |
| first_indexed | 2024-12-17T21:30:00Z |
| format | Article |
| id | doaj.art-20754131aa8a4f32864f1733ed6cf20a |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-17T21:30:00Z |
| publishDate | 2010-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-20754131aa8a4f32864f1733ed6cf20a2022-12-21T21:31:55ZengElsevierNeurobiology of Disease1095-953X2010-02-01372412422Functional over-load saves motor units in the SOD1-G93A transgenic mouse model of amyotrophic lateral sclerosisT. Gordon0N. Tyreman1S. Li2C.T. Putman3J. Hegedus4Center for Neuroscience, University of Alberta, Edmonton, AB, Canada T6G 2S2; Division of Rehabilitation and Physical Medicine, Faculty of Medicine, University of Alberta, Edmonton, AB, Canada T6G 2S2; Corresponding author. Division of Physical Medicine and Rehabilitation/Centre for Neuroscience 525 Heritage Medical Research Centre Faculty of Medicine and Dentistry, University of Alberta Edmonton, AB, Canada T6G 2S2. Fax: +1 780 492 1617.Center for Neuroscience, University of Alberta, Edmonton, AB, Canada T6G 2S2; Division of Rehabilitation and Physical Medicine, Faculty of Medicine, University of Alberta, Edmonton, AB, Canada T6G 2S2Center for Neuroscience, University of Alberta, Edmonton, AB, Canada T6G 2S2; Division of Rehabilitation and Physical Medicine, Faculty of Medicine, University of Alberta, Edmonton, AB, Canada T6G 2S2Center for Neuroscience, University of Alberta, Edmonton, AB, Canada T6G 2S2; Exercise Biochemistry Laboratory, Faculty of Physical Education and Recreation, University of Alberta, Edmonton, AB, Canada T6G 2H9Center for Neuroscience, University of Alberta, Edmonton, AB, Canada T6G 2S2; Division of Rehabilitation and Physical Medicine, Faculty of Medicine, University of Alberta, Edmonton, AB, Canada T6G 2S2The fastest, most forceful motor units are lost progressively during asymptomatic disease in the SOD1G93A transgenic mouse model of amyotrophic lateral sclerosis. As the disease progresses the surviving motor units must increase their levels of activity to sustain posture and movement. If activity-dependent conversion of motor units to more fatigue resistant types increased their resilience and hence survival, we hypothesized that an experimental increase in motor unit activity in the hindlimb muscles of the SOD1G93A transgenic mouse should “save” those motor units that are normally lost in the first 90 days of age. To test this hypothesis, we partially denervated hindlimb muscles in SOD1G93A and their corresponding control SOD1WT transgenic mice by avulsion of either L4 or L5 spinal roots at 40 days of age. Whole muscle and single motor unit isometric twitch forces were recorded and the numbers intact motor units in fast-twitch tibialis anterior, medial gastrocnemius, extensor digitorum longus muscles and the slow-twitch soleus muscle were calculated at 90 days of age. We found that the rapid age-dependent decline in numbers of functional motor units in fast-twitch muscles of the SOD1G93A transgenic mice was dramatically reduced by the functional hyperactivity in the partially denervated muscles and, that these muscles comprised a significantly higher component of type IIA and type IID/X fibers than those muscles that were innervated by nerves in intact spinal roots. We conclude that the vulnerable motor units are saved by increasing their neuromuscular activity and consequently, converting them to slower, less forceful, fatigue resistant motor units.http://www.sciencedirect.com/science/article/pii/S0969996109003076Amyotrophic Lateral SclerosisMotor UnitActivityMotoneuronDenervationNeuromuscular |
| spellingShingle | T. Gordon N. Tyreman S. Li C.T. Putman J. Hegedus Functional over-load saves motor units in the SOD1-G93A transgenic mouse model of amyotrophic lateral sclerosis Neurobiology of Disease Amyotrophic Lateral Sclerosis Motor Unit Activity Motoneuron Denervation Neuromuscular |
| title | Functional over-load saves motor units in the SOD1-G93A transgenic mouse model of amyotrophic lateral sclerosis |
| title_full | Functional over-load saves motor units in the SOD1-G93A transgenic mouse model of amyotrophic lateral sclerosis |
| title_fullStr | Functional over-load saves motor units in the SOD1-G93A transgenic mouse model of amyotrophic lateral sclerosis |
| title_full_unstemmed | Functional over-load saves motor units in the SOD1-G93A transgenic mouse model of amyotrophic lateral sclerosis |
| title_short | Functional over-load saves motor units in the SOD1-G93A transgenic mouse model of amyotrophic lateral sclerosis |
| title_sort | functional over load saves motor units in the sod1 g93a transgenic mouse model of amyotrophic lateral sclerosis |
| topic | Amyotrophic Lateral Sclerosis Motor Unit Activity Motoneuron Denervation Neuromuscular |
| url | http://www.sciencedirect.com/science/article/pii/S0969996109003076 |
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