Extensive exercise is not harmful in amyotrophic lateral sclerosis

Abstract

Whether physical activity increases risk or promotes progression of motor neurone degeneration in amyotrophic lateral sclerosis (ALS) is still debated. Current pathophysiological hypotheses include excitotoxicity, oxidative stress and increased calcium loads as causes of selective degeneration of vulnerable motor neurones. Vigorous exercise might amplify these factors by increasing firing rates at motor neurones. To test this hypothesis, we constrained a transgenic mouse model of ALS overexpressing the mutant human form of the Cu/Zn superoxide dismutase-1 (SOD-1) to a lifetime exercise on motor-driven running wheels for 10 h daily (active group, n = 12). Onset and progression of disease were assessed by grip strength, stride length and tight rope test. Data were compared with SOD-1 mice placed in running wheels set to slow speed (sedentary group, n = 13). Untreated SOD-1 mice were an additional control group (n = 12). We found no differences in disease onset, which was determined by a change-point analysis using an iterative fitting of segmented linear regression models, or in disease progression. However, the running group showed a non-significant 6-day improvement in survival (133.7 +/- 3.2 days) compared with the sedentary group (127.2 +/- 3.2 days) and a 4-day improvement compared with the control group (129.1 +/- 2.5 days). We demonstrate that a lifetime of vigorous exercise does not promote onset or progression of motor degeneration in SOD-1-mediated ALS. Moreover, the results suggest that the level of excitatory input and calcium turnover at motor neurones, both of which should be increased by running activity, do not interfere with the pathophysiology of SOD-1-mediated ALS.

Sports and trauma in amyotrophic lateral sclerosis revisited

“…Studies in transgenic mouse models have provided conflicting data. One report showed that extensive exercise did not promote disease onset or progression in SOD1-mutant mice [19], whereas another report [20] suggested that exercise in transgenic mice was beneficial, and a third report [21] suggested that it was harmful. For the present, there is a consistent pattern of well-designed studies showing no link between physical activity and sporadic ALS.…”

Regular Exercise Prolongs Survival in a Type 2 Spinal Muscular Atrophy Model Mouse

“…Many studies have been devoted to the effect of physical exercise on neurological disorders. Clinical observations confirm the efficiency of exercise in alleviating the symptoms in a variety of neurodegenerative diseases and, more specifically, neuromuscular disease such as amyotrophic lateral sclerosis (Kirkinezos et al, 2003;Veldink et al, 2003;Liebetanz et al, 2004;Mahoney et al, 2004). The potential rehabilitative role of exercise training has not been addressed in SMA.…”

Chronic Treatment with the AMPK Agonist AICAR Prevents Skeletal Muscle Pathology but Fails to Improve Clinical Outcome in a Mouse Model of Severe Spinal Muscular Atrophy

“…The potential role of physical exercise as an adjunct therapy in MN disorders has been studied in mouse models of amyotrophic lateral sclerosis and SMA [35][36][37][38][39]. Thus, regular exercise has been reported to improve motor function significantly, prolong lifespan, protect MNs from death, and attenuate muscular atrophy in mice mimicking SMA type II [38].…”