title: (-)-Deprenyl alters the survival of adult murine facial motoneurons after axotomy: increases in vulnerable C57BL strain but decreases in motor neuron degeneration mutants.
abstract: The effect of (-)-deprenyl on the survival of axotomized adult murine facial motoneurons was investigated. Previously, (-)-deprenyl was shown to increase the number of rat facial motoneurons (FMns) surviving after axotomy at postnatal day 14, apparently by compensating for the loss of muscle-derived trophic factor. In the present study, three different strains of adult mice--A/J, C57BL/6J, and a congenic substrain of the C57BL/6J mice, the C57BL/Mnd mutants--underwent unilateral facial nerve 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 axotomy. 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 the A/J strain was 90% of unlesioned, control values which supports previous findings that adult FMns receive adequate trophic support and thus can survive loss of muscle-derived trophic support. In the C57BL/6J strain, the facial motoneuron survival was 35% and (-)-deprenyl increased the survival to 50.5%. Mnd mutants showed 62.4% survival; however, (-)-deprenyl decreased the number of motoneurons to 54.9% and amphetamine and methamphetamine treatment further decreased the motoneuron survival to 41.1%. These findings show that FMns in the Mnd mutants and their parental strain, C57BL/6J mice, show greater vulnerability to axotomy as compared to other adult strains of mice. The vulnerability is similar to that found in early postnatal life. (-)-Deprenyl increases the survival of the axotomized C57BL/6J FMns but its major metabolites, (-)-methamphetamine and (-)-amphetamine, further decrease FMn survival in the C57BL/Mnd mutants, possibly due to the induction of neurotoxic proteins causing programmed neuronal death. The efficacy of (-)-deprenyl in increasing the survival of damaged neurons would be expected to decrease as dosage increased above the dosage sufficient to induce maximum neuronal rescue (approximately 0.01 mg/kg) but would decrease as the dosage exceeded that necessary to produce toxic concentrations of the metabolites of (-)-deprenyl (1.0 mg/kg in this study).
authors.affiliation: Department of Physiology, University of Toronto, Ontario, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Oh
authors.forename: B
authors.initials: B
authors.lastname: Murray
authors.forename: N
authors.initials: N
authors.lastname: Bhattacharya
authors.forename: D
authors.initials: D
authors.lastname: Holland
authors.forename: W G
authors.initials: WG
authors.lastname: Tatton
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001369:Axons / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D005154:Facial Nerve / Q000166:cytology* / Q000502:physiology; D008694:Methamphetamine / Q000494:pharmacology; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D009046:Motor Neurons / Q000187:drug effects*; D009410:Nerve Degeneration / Q000502:physiology*; D012642:Selegiline / Q000494:pharmacology*; D013045:Species Specificity
chemical_list: D012642:Selegiline; D008694:Methamphetamine; D000661:Amphetamine