Title:Wheel Running Adversely Affects Disease Onset and Neuromuscular
Interplay in Amyotrophic Lateral Sclerosis Slow Progression Mouse Model
Volume: 20
Issue: 3
Author(s): Elisabetta Golini, Sara Marinelli, Simona Pisu, Federica De Angelis, Valentina Vacca, Alessandro Rava, Irene Casola, Gaia Laurenzi, Emanuele Rizzuto, Alessandro Giuliani, Antonio Musarò*, Gabriella Dobrowolny and Silvia Mandillo
Affiliation:
- DAHFMO-Unit of Histology and Medical Embryology, Laboratory Affiliated to Istituto Pasteur Italia-
Fondazione Cenci Bolognetti, University of Roma "La Sapienza", Rome, Italy
Keywords:
SOD1G93A low-copy, exercise, mouse behavior, neuromuscular junction functionality, home cage monitoring, wheel running, ALS, physical activity.
Abstract:
Background: Physical activity in Amyotrophic Lateral Sclerosis (ALS) plays a controversial
role. In some epidemiological studies, both recreational or professional sport exercise has
been associated to an increased risk for ALS but the mechanisms underlying the effects of exercise
have not been fully elucidated in either patients or animal models.
Methods: To better reproduce the influence of this environmental factor in the pathogenesis of
ALS, we exposed SOD1G93A low-copy male mice to multiple exercise sessions at asymptomatic
and pre-symptomatic disease stages in an automated home-cage running-wheel system for about 3
months.
Results: Repeated voluntary running negatively influenced disease progression by anticipating
disease onset, impairing neuromuscular transmission, worsening neuromuscular decline, and exacerbating
muscle atrophy. Muscle fibers and neuromuscular junctions (NMJ) as well as key molecular
players of the nerve-muscle circuit were similarly affected.
Conclusion: It thus appears that excessive physical activity can be detrimental in predisposed individuals
and these findings could model the increased risk of developing ALS in predisposed and
specific professional athletes.
