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The influence of metallothionein treatment and treadmill running exercise on disease onset and survival in SOD1G93A amyotrophic lateral sclerosis mice
journal contribution
posted on 2023-05-20, 16:29 authored by Katherine LewisKatherine Lewis, William BennettWilliam Bennett, Christopher BlizzardChristopher Blizzard, Adrian WestAdrian West, Chung, RS, Meng Inn ChuahMeng Inn ChuahAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, characterised by the degeneration of motor neurons innervating skeletal muscle. The mechanisms underlying neurodegeneration in ALS are not yet fully elucidated, and with current therapeutics only able to extend lifespan by a matter of months there is a clear need for novel therapies to increase lifespan and patient quality of life. Here, we evaluated whether moderate-intensity treadmill exercise and/or treatment with metallothionein-2 (MT2), a neuroprotective protein, could improve survival, behavioural or neuropathological outcomes in SOD1G93A familial ALS mice. Six-week-old female SOD1G93A mice were allocated to one of four treatment groups: MT2 injection, i.m.; moderate treadmill exercise; neither MT2 nor exercise; or both MT2 and exercise. MT2-treated mice survived around 3% longer than vehicle-treated mice, with this mild effect reaching statistical significance in Cox proportional hazards analysis once adjusted for potential confounders. Mixed model body weight trajectories over time indicated that MT2-treated mice, with or without exercise, reached maximum body weight at a later age, suggesting a delay in disease onset of around 4% compared to saline-treated mice. Exercise alone did not significantly increase survival or delay disease onset, and neither exercise nor MT2 substantially ameliorated gait abnormalities or muscle strength loss. We conclude that neither exercise nor MT2 treatment was detrimental in female SOD1G93A mice, and further study could determine whether the mild effect of peripheral MT2 administration on disease onset and survival could be improved via direct administration of MT2 to the central nervous system.
History
Publication title
European Journal of NeuroscienceVolume
52Issue
4Pagination
3223-3241ISSN
0953-816XDepartment/School
Menzies Institute for Medical ResearchPublisher
Blackwell Publishing LtdPlace of publication
9600 Garsington Rd, Oxford, England, Oxon, Ox4 2DgRights statement
© 2020 Federation of European Neuroscience Societies and John Wiley & Sons LtdRepository Status
- Restricted