Can inadequacy of rest between high-intensity exercises predispose for glutamate excitotoxicity among people at risk of motor neuron disease?

Motor neuron disease (MND) is characterized pathologically by degenerative changes in the anterior horn cells, motor nuclei of the brainstem, and the corticospinal tracts. Several theories have been proposed to understand the etiology of MND. Glutamate excitotoxicity is one of the important theories that explain the pathogenesis of MND. Theories have argued participation in high-intensity exercises leads to excessive glutamate production and glutamate excitotoxicity which further leads to neuronal death and incidence of MND. However, to date, none of the studies/authors have explored the importance of rest periods in glutamate reabsorption. We argue that lack of adequate rest periods between the bouts of high-intensity exercises can be a potential risk factor for developing MND, rather than engaging in high-intensity exercise itself. In this short communication, we propose an interesting postulate on the role of rest periods in the prevention of glutamate excitotoxicity.