Electrophysiological analysis of a murine model of motoneuron disease.

Objective: amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by loss of motoneurons of the primary motor cortex, the brainstem and the spinal cord, for which there are not effective treatments. Several transgenic mice that mimic motoneuron disease have been used to investigate potential treatments. The objective of this work is to characterize electrophysiologically the SOD1G93A transgenic mouse model of ALS, and to provide useful markers to improve early detection and monitoring of progression of the disease.Methods: we performed nerve conduction tests, motor unit number estimation (MUNE), H reflex tests and motor evoked potentials (MEPs) in a cohort of transgenic and wild type mice from 4 to 16 weeks of age.Results: the results revealed dysfunction of spinal motoneurons evidenced by deficits in motor nerve conduction tests starting at 8 weeks of age, earlier in proximal than in distal muscles of the hindlimb. MUNE demonstrated that spinal motoneurons loss muscle innervation and have a deficit in their sprouting capacity. Motor evoked potentials revealed that, coexisting with peripheral deficits, there was a dysfunction of central motor tracts that started also at 8 weeks, indicating progressive dysfunction of upper motoneurons.Conclusions: these electrophysiological results provide important information about the SOD1G93A mouse model, as they demonstrate by the first time alterations of central motor pathways simultaneously to lower motoneuron dysfunction, well before functional abnormalities appear (by 12 weeks of age).Significance: the finding of concomitant dysfunction of upper and lower motoneurons contributes to the validation of the SOD1G93A mouse as model of ALS, because this parallel involvement is a diagnostic condition for ALS. Electrophysiological tests can be used as early markers of the disease and to evaluate the potential benefits of new treatments on both upper and lower motoneuron