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The influence of metallothionein treatment and treadmill running exercise on disease onset and survival in SOD1G93A amyotrophic lateral sclerosis mice
Citation
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
Abstract
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 |
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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 |
Downloads: | 0 |
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