Fatigability of spinal reflex transmission in a mouse model (SOD1(G93A) ) of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive loss of motor neurons. To analyze the progressive motor deficits during the course of this disease, we investigated fatigability and ability of recovery of spinal motor neurons by testing monosynaptic reflex transmission with increasing stimulus frequencies in the lumbar spinal cord of the SOD1(G93A) mouse model for ALS in a comparison with wild-type (WT) mice. Monosynaptic reflexes in WT and SOD1(G93A) mice without behavioral deficits showed no difference with respect to their resistance to increasing stimulus frequencies. During the progression of motor deficits in SOD1(G93A) mice, the vulnerability of monosynaptic reflexes to higher frequencies increased, the required time for reflex recovery was extended, and recovery was often incomplete. Fatigability and demand for recovery of spinal motor neurons in SOD1(G93A) mice rose with increasing motor deficits. This supports the assumption that impairment of the energy supply may contribute to the pathogenesis of ALS.