Functional over-load saves motor units in the SOD1-G93A transgenic mouse model of amyotrophic lateral sclerosis

Motor Unit Survival in Lifelong Runners Is Muscle Dependent

“…In contrast, moderate wholebody endurance exercise (30 min of swimming 3 d-wk~') had a protective effect on MN numbers compared to agematched controls (23). In addition, increased neuromuscular activity (through partial denervation of a spinal nerve root) in an ALS transgenic mouse model prevented the large (40%-70% loss) reduction in MN usually observed in this particular diseased mouse model of accelerated neuromuscular aging (16). It seems, based on the findings from the few available studies, that lifelong physical activity of moderate intensity may be more effective in preserving MU numbers than short bouts of resistance-type training.…”

“…This could be in part due to technical limitations of the method (17). The very low level voluntary contractions (i.e., 1-5 MVC) used by Doherty et al (13) may have biased S-MUP recordings toward recording fi-om the lowest threshold and most detectable MUs, which, presumably, would show greater collateral reinnervation than higher threshold units (16). Thus, by using a higher load of 10% MVC, in addition to the lowest threshold units, we would also be sampling from higher threshold MUs that may exhibit less collateral reinnervation.…”

“…The loss of MUs occurs in a regressive manner, with the denervation of muscle preceding the loss of motor axons and eventual a-MN death (10,16). As a compensatory mechanism, healthy MUs (often Type I) can sprout new collateral axonal branches to reinnervate those muscle fibers orphaned (often Type II) after the death of their parent MN.…”

Amyotrophic lateral sclerosis: Current perspectives from basic research to the clinic

“…In contrast, mSOD1 MNs were unable to 1313 down-regulate their KCC2 and thus not becoming hyperexcitable 1314 even when already disconnected from their muscles (Mò dol et al, 1315(Mò dol et al, 2014. Further studies revealed that functional overload is able to 1316 rescue motor units in mSOD1 G93A mice (Gordon et al, 2010), 1317 supporting the hypothesis of hypoexcitability as one potential factor 1318 underlying selective MN damage.…”

Neuregulin-1 promotes functional improvement by enhancing collateral sprouting in SOD1G93A ALS mice and after partial muscle denervation

“…To further understand the role of Nrg1 on axonal collateral sprouting, we used a model of hindlimb muscle partial denervation, consisting in postganglionic axotomy of the L4 spinal nerve (rhyzotomy) in wild type mice (Gordon et al, 2010) (Fig. 6a).…”