title: Signaling events in axons and/or dendrites render motor neurons vulnerable to mutant superoxide dismutase toxicity.
abstract: The survival of dorsal root ganglion and sympathetic neurons is promoted whether nerve growth factor (NGF) activates TrkA receptors on the cell body or the axon. Yet other aspects of neurotrophic factor actions (i.e., ability to promote axon growth, selection of neurochemical phenotype and engagement of signaling modules) differ as a function of the location of the ligand-receptor interaction. The extent to which these observations are relevant to CNS neurons is unknown. This may be particularly relevant to neurodegenerative diseases such as amyotrophic lateral sclerosis, where beneficial axon-target interactions are disturbed early in the disease process. Here we characterize the growth of pure motor neurons in compartment cultures and show that brain-derived neurotrophic factor (BDNF) stimulation of the cell body or axons/dendrites promotes survival. Expression of G37R mutant superoxide dismutase (SOD) in motor neurons will lead to death and this depends on BDNF activation of TrkB on axons and/or dendrites. BDNF action depends upon endocytosis of the BDNF-TrkB complex and de novo protein synthesis. These results highlight the importance of signaling events occurring in axons/dendrites in mutant SOD toxicity.
authors.affiliation: Division of Neurology, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Goo-Bo
authors.initials: GB
authors.lastname: Jeong
authors.forename: Jelena
authors.initials: J
authors.lastname: Mojsilovic-Petrovic
authors.forename: Marco
authors.initials: M
authors.lastname: Boccitto
authors.forename: Robert
authors.initials: R
authors.lastname: Kalb
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000235:genetics; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D019921:Biotinylation; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D003712:Dendrites / Q000187:drug effects / Q000502:physiology*; D004622:Embryo, Mammalian; D004705:Endocytosis / Q000187:drug effects / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D005998:Glycine / Q000235:genetics; D047468:Immunoprecipitation / Q000379:methods; D009046:Motor Neurons / Q000166:cytology* / Q000187:drug effects; D009154:Mutation / Q000235:genetics*; D051381:Rats; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*; D018139:Simplexvirus / Q000235:genetics / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology; D013482:Superoxide Dismutase / Q000235:genetics*; D014162:Transfection / Q000379:methods
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D004791:Enzyme Inhibitors; D001120:Arginine; D013482:Superoxide Dismutase; D020813:Receptor, trkB; D005998:Glycine