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The influence of metallothionein treatment and treadmill running exercise on disease onset and survival in SOD1G93A amyotrophic lateral sclerosis mice


Lewis, KEA and Bennett, W and Blizzard, CL and West, AK and Chung, RS and Chuah, MI, The influence of metallothionein treatment and treadmill running exercise on disease onset and survival in SOD1G93A amyotrophic lateral sclerosis mice, European Journal of Neuroscience, 52, (4) pp. 3223-3241. ISSN 0953-816X (2020) [Refereed Article]

Copyright Statement

2020 Federation of European Neuroscience Societies and John Wiley & Sons Ltd

DOI: doi:10.1111/ejn.14682


Amyotrophic 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.

Item Details

Item Type:Refereed Article
Keywords:antioxidant, metallothionein-2, mixed modelling, neurodegeneration, treadmill exercise
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Neurology and neuromuscular diseases
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Lewis, KEA (Dr Katherine Lewis)
UTAS Author:Bennett, W (Dr Bill Bennett)
UTAS Author:Blizzard, CL (Professor Leigh Blizzard)
UTAS Author:West, AK (Professor Adrian West)
UTAS Author:Chuah, MI (Associate Professor Inn Chuah)
ID Code:140117
Year Published:2020
Deposited By:Medicine
Deposited On:2020-07-28
Last Modified:2021-09-03

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