TUMOR-NECROSIS-FACTOR IS INCREASED IN THE SPINAL-CORD OF AN ANIMAL-MODEL OF MOTOR-NEURON DEGENERATION

Autoimmunity and oxidative/excitotoxic damage are considered as possib le pathogenetic mechanisms in amyotrophic lateral sclerosis (ALS), As tumor necrosis factor (TNF) is implicated in autoimmune diseases, incl uding experimental autoimmune encephalomyelitis, and can be neurotoxic , we studied TNF production in a proposed animal model of ALS, the mnd mouse. These mice develop symptoms (progressive weakness of the limbs ) as late as at 7 months of age, We measured TNF in serum, brain and s pinal cord of mnd mice at 3 and 7 months of age, TNF was detectable in the brain and spinal cord (but not in the serum) at 7 months, while n o TNF was detected in mnd mice at 3 months (asymptomatic) or in contro l mice of the same genetic background and the same age, Immunohistoche mistry confirmed localization of TNF-a in motor neurons situated in th e ventral horn of the spinal cord of 7-month old mnd mice. These resul ts suggest the possibility of testing inhibitors of TNF production in this disease.