Unlike physical exercise, modified environment increases the lifespan of SOD1G93A mice however both conditions induce cellular changes

PLoS One. 2012;7(9):e45503. doi: 10.1371/journal.pone.0045503. Epub 2012 Sep 20.


Background: Amyotrophic lateral sclerosis (ALS) is characterized by a gradual muscular paralysis resulting from progressive motoneurons death. ALS etiology remains unknown although it has been demonstrated to be a multifactorial disease involving several cellular partners. There is currently no effective treatment. Even if the effect of exercise is under investigation for many years, whether physical exercise is beneficial or harmful is still under debate.

Methods and findings: We investigated the effect of three different intensities of running exercises on the survival of SOD1(G93A) mice. At the early-symptomatic stage (P60), males were isolated and randomly assigned to 5 conditions: 2 sedentary groups ("sedentary" and "sedentary treadmill" placed on the inert treadmill), and 3 different training intensity groups (5 cm/s, 10 cm/s and 21 cm/s; 15 min/day, 5days/week). We first demonstrated that an appropriate "control" of the environment is of the utmost importance since comparison of the two sedentary groups evidenced an 11.6% increase in survival in the "sedentary treadmill" group. Moreover, we showed by immunohistochemistry that this increased lifespan is accompanied with motoneurons survival and increased glial reactivity in the spinal cord. In a second step, we showed that when compared with the proper control, all three running-based training did not modify lifespan of the animals, but result in motoneurons preservation and changes in glial cells activation.

Conclusions/significance: We demonstrate that increase in survival induced by a slight daily modification of the environment is associated with motoneurons preservation and strong glial modifications in the lumbar spinal cord of SOD1(G93A). Using the appropriate control, we then demonstrate that all running intensities have no effect on the survival of ALS mice but induce cellular modifications. Our results highlight the critical importance of the control of the environment in ALS studies and may explain discrepancy in the literature regarding the effect of exercise in ALS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / mortality
  • Animals
  • Environment
  • Life Expectancy*
  • Male
  • Mice
  • Motor Neurons / metabolism
  • Neuroglia / metabolism
  • Neuromuscular Junction / metabolism
  • Physical Exertion*
  • Spinal Cord / cytology
  • Spinal Cord / metabolism
  • Superoxide Dismutase / genetics*
  • Superoxide Dismutase / metabolism*


  • SOD1 G93A protein
  • Superoxide Dismutase

Grants and funding

This study was supported by the Fondation de l’Avenir [ET7–456 to FEP], the Spanish Government, Plan Nacional de I+D+I 2008–2011 and ISCIII - Subdirección General de Evaluación y Fomento de la Investigación [PI10/00709 to FEP], the Basque Government, Fondo Común de Cooperación Aquitania-Euskadi and Proyectos de Investigacion Sanitaria [to FEP], the Association Demain Debout Aquitaine [to YNG] and the Swiss National Science Foundation [to ACK]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.