title: GDNF is trophic for mouse motoneurons that express a mutant superoxide dismutase (SOD-1) gene.
abstract: METHODS
  An in vitro system of motoneurons was established from mice carrying a transgene for a human superoxide dismutase-1 (SOD-1) with a gly93ala mutation that has been linked to familial amyotrophic lateral sclerosis (FALS). These cultures were characterized and used to compare the effects of glial cell line-derived neurotrophic factor (GDNF) on motoneurons expressing the mutant gene with those on normal motoneurons.
  
  
  RESULTS
  Recombinant human GDNF (100 ng/ml) significantly promoted the survival of a subpopulation of choline acetyltransferase (ChAT)-immunoreactive motoneurons that were also immunoreactive for the homeoprotein islet-1 in cultures from both wild type and mutant SOD-1 mice. However, GDNF did not increase the total number of ChAT-immunoreactive neurons in cultures from either wild type or transgenic mice. A distinct subpopulation of islet-1-immunoreactive motoneurons characterized by a soma 3 1/2 times larger and a ten-fold increase in neurite length was observed exclusively in GDNF-treated cultures. In cultures from mutant SOD-1 mice, there were 3 1/2 times as many motoneurons of this subpopulation as in wild type cultures at 6 days in vitro. In addition, this subpopulation of neurons survived for 10 days in vitro, the longest time point studied, in culture from mutant SOD-1 mice, but not in cultures from wild type mice. This subpopulation was also present at 6 days in vitro in cultures from mutant SOD-1 mice that received GDNF at 3 days in vitro instead of at the time of plating, suggesting that GDNF promotes the differentiation of these neurons.
  
  
  CONCLUSIONS
  Our observations suggest that the expression of a mutant SOD-1 gene, as occurs in familial ALS, does not compromise the trophic effects of GDNF on motoneuron survival, but may affect the development of motoneurons.
authors.affiliation: Program in Neuroscience, University of Rochester Medical Center, Northwestern University Medical School, Chicago, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Derby
authors.forename: R
authors.initials: R
authors.lastname: Giuliano
authors.forename: D A
authors.initials: DA
authors.lastname: Figlewicz
authors.forename: M C
authors.initials: MC
authors.lastname: Bohn
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017354:Point Mutation; D011247:Pregnancy; D013116:Spinal Cord / Q000166:cytology; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1
chemical_list: C495040:Gdnf protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1