Excitability properties of mouse motor axons in the mutant SOD1(G93A) model of amyotrophic lateral sclerosis.
Non-invasive excitability studies of motor axons in patients with amyotrophic lateral sclerosis (ALS) have revealed a changing pattern of abnormal membrane properties with disease progression, but the heterogeneity of the changes has made it difficult to relate them to pathophysiology. The SOD1(G93A) mouse model of ALS displays more synchronous motoneuron pathology. Multiple excitability measures of caudal and sciatic nerves in mutant and wild-type mice were compared before onset of signs and during disease progression (4-19 weeks), and they were related to changes in muscle fiber histochemistry. Excitability differences indicated a modest membrane depolarization in SOD1(G93A) axons at about the time of symptom onset (8 weeks), possibly due to deficient energy supply. Previously described excitability changes in ALS patients, suggesting altered sodium and potassium conductances, were not seen in the mice. This suggests that those changes relate to features of the human disease that are not well represented in the animal model.
Boërio
Delphine
D
Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Kalmar
Bernadett
B
Greensmith
Linda
L
Bostock
Hugh
H
D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology / Q000235:genetics*; D000818:Animals; D001369:Axons / Q000473:pathology* / Q000502:physiology; D004195:Disease Models, Animal; D004558:Electric Stimulation; D006801:Humans; D051379:Mice; D009046:Motor Neurons / Q000473:pathology* / Q000502:physiology; D009154:Mutation; D010525:Peripheral Nerves / Q000473:pathology / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide; D013482:Superoxide Dismutase / Q000235:genetics*; D013623:Tail / Q000294:innervation; D013979:Tibial Nerve / Q000473:pathology / Q000503:physiopathology
D013482:Superoxide Dismutase