(-)-DEPRENYL ALTERS THE SURVIVAL OF ADULT MURINE FACIAL MOTONEURONS AFTER AXOTOMY - INCREASES IN VULNERABLE C57BL STRAIN BUT DECREASES IN MOTOR-NEURON DEGENERATION MUTANTS

The effect of (-)-deprenyl on the survival of axotomized adult murine facial motoneurons was investigated. Previously, (-)-deprenyl was show n to increase the number of rat facial motoneurons (FMns) surviving af ter axotomy at postnatal day 14, apparently by compensating for the lo ss of muscle-derived trophic factor. In the present study, three diffe rent strains of adult mice-A/J, C57BL/6J, and a congenic substrain of the C57BL/6J mice, the C57BL/Mnd mutants-underwent unilateral facial n erve transection. FMns were counted from serial sections taken through the entire length of the facial nuclei ipsilateral and contralateral to the facial nerve transections in animals sacrificed 21 days after a xotomy. Subgroups of C57BL/6J and Mnd mutants were treated with either saline or 1.0 mg/kg (-)-deprenyl for 21 days. Another subgroup of Mnd mutants were treated with the metabolites of (-)-deprenyl, a mixture of (-)-amphetamine and (-)-methamphetamine, at a dosage equimolar to 1 .0 mg/kg (-)-deprenyl. The number of surviving facial motoneurons in t he A/J strain was 90% of unlesioned, control values which supports pre vious findings that adult FMns receive adequate trophic support and th us can survive loss of muscle-derived trophic support. In the C57BL/6J strain, the facial motoneuron survival was 35% and (-)-deprenyl incre ased the survival to 50.5%. Mnd mutants showed 62.4% survival; however , (-)-deprenyl decreased the number of motoneurons to 54.9% and amphet amine and methamphetamine treatment further decreased the motoneuron s urvival to 41.1%. These findings show that FMns in the Mnd mutants and their parental strain, C57BL/6J mice, show greater vulnerability to a xotomy as compared to other adult strains of mice. The vulnerability i s similar to that found in early postnatal life. (-)-Deprenyl increase s the survival of the axotomized C57BL/6J FMns but its major metabolit es, (-)-methamphetammine and (-)-amphetamine, further decrease FMn sur vival in the C57BL/Mnd mutants, possibly due to the induction of neuro toxic proteins causing programmed neuronal death. The efficacy of (-)- deprenyl in increasing the survival of damaged neurons would be expect ed to decrease as dosage increased above the dosage sufficient to indu ce maximum neuronal rescue (approximately 0.01 mg/kg) but would decrea se as the dosage exceeded that necessary to produce toxic concentratio ns of the metabolites of (-)-deprenyl (1.0 mg/kg in this study). (C) 1 994 Wiley-Liss, Inc.