The Effect of Training on Motoneuron Survival in Amyotrophic Lateral Sclerosis: Which Motoneuron Type is Saved?

Amyotrophic lateral sclerosis (ALS) is characterized by selective and progressive degeneration of motoneurons (MNs). Although the etiology of the disease is unknown, glutamate toxicity and reac-tive oxygen species toxicity have been strongly implicated in ALS pathophysiol-ogy, Training exercise has been proposed to provide a beneficial therapy during the early or late stages of ALS (Pinto et al., 1999; Drory et al., 2001); however, some studies showed deleterious effects of exercise on survival in ALS (Mahoney et al., 2004). The beneficial effects are based on the cellular adaptations induced by training exercise in the brain, spinal cord, and skeletal muscles that could counteract the oxidative stress complication in ALS. For instance, training exercise increases the capacity of antioxi-dant enzymes and reduces lipid perox-ides in brain regions of rats (Somani and Husain, 1997; Husain and Somani, 1998). In skeletal muscle, training reduces oxidative stress following exercise (Miyazaki et al., 2001), increases the mitochondrial capacity (Holloszy et al., 1970), and increases the expression of neurotrophic factors (Gomez-Pinilla et al., 2001). The latter could be particularly beneficial in ALS because neurotrophic factors could prevent MN degeneration, preserve muscle inner-vation, and inhibit muscle atrophy (Acsadi et al., 2002; Manabe et al., 2002; Sun et al., 2002). Therefore, it is conceivable that training exercise could be beneficial by resisting oxidative stress and offsetting energy deficits caused by mitochondrial dysfunction in ALS. In a recent study, training exercise has been also shown to have neuroprotec-tive effects in the spinal cord by saving MNs from degeneration, in addition to maintaining muscle fiber composition (Deforges et al., 2009). The Deforges et al. (2009) study is important for understanding the effect of training exercise in ALS because it compared two training paradigms and showed differential neuroprotective effects in the spinal cord. Here we discuss the methodology and interpretation from the Deforges et al. (2009) study on which MN type is saved by training exercise, and try to reconcile their conclusions with the literature and more recent work. Deforges et al. (2009) examined the effect of two training exercise paradigms (i.e., running and swimming) on MN survival and muscle fiber composition in the G93A (high expressor line) mouse model of ALS. In comparison to other ALS mouse models, this model has high level of expression of the mutant human SOD1 gene, rapid disease onset, and short life span. Training exercise was performed through 30 min daily running or swimming sessions that …