BRAIN-DERIVED NEUROTROPHIC FACTOR FAILS TO ARREST NEUROMUSCULAR DISORDERS IN THE PARALYZE MOUSE MUTANT, A MODEL OF MOTONEURON DISEASE

Several new neurotrophic factors have been recently identified and sho wn to prevent motoneuron death in vitro and in vivo. One such agent is brain-derived neurotrophic factor (BDNF). In this study, we tested BD NF on an animal model of early-onset motoneuron disease: the paralyse mouse mutant, characterized by a progressive skeletal muscle atrophy a nd the loss of 30-35% of spinal lumbar motoneurons between the first a nd second week post-natal. The results show that subcutaneous injectio ns of 1 or 10 mg/kg BDNF did not have any significant effect in increa sing the mean survival time of mutant mice or in preventing the loss o f motor function and total body weight in paralyse mice. The weight an d choline acetyltransferase activity of specific muscles and the numbe r of motoneurons in the spinal cords were identical in BDNF-treated an d placebo-injected paralyse mice. These results suggest that BDNF does not act on the disease profess in paralyse mice in the conditions we used. By contrast, BDNF has previously been shown to partially prevent the loss of motor function in the wobbler mouse, a suggested model of later-onset motoneuron disease. Taken together these findings suggest that BDNF acts differently on early and late-onset motoneuron disease s. It is however possible that treatment of paralyse mice with BDNF or combinations of different neurotrophic factors prior to the phenotypi cal expression of the paralyse mutation may prevent the loss of motor function and motoneurons in mutant mice. (C) 1997 Elsevier Science B.V .