title: Glial cell line-derived neurotrophic factor (GDNF) is a neurotrophic factor for sensory neurons: comparison with the effects of the neurotrophins.
abstract: We compared the effects of glial cell line-derived neurotrophic factor (GDNF) on dorsal root ganglion (DRG) sensory neurons to that of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin 3 (NT-3). All of these factors were retrogradely transported to subpopulations of sensory neuron cell bodies in the L4/ L5 DRG of neonatal rats. The size distribution of 125I-GDNF-labeled neurons was variable and consisted of both small and large DRG neurons (mean of 506.60 microns2). 125I-NGF was preferentially taken up by small neurons with a mean cross-sectional area of 383.03 microns2. Iodinated BDNF and NT-3 were transported by medium to large neurons with mean sizes of 501.48 and 529.27 microns2, respectively. A neonatal, sciatic nerve axotomy-induced cell death model was used to determine whether any of these factors could influence DRG neuron survival in vivo. GDNF and NGF rescued nearly 100% of the sensory neurons. BDNF and NT-3 did not promote any detectable level of neuronal survival despite the fact that they underwent retrograde transport. We examined the in vitro survival-promoting ability of these factors on neonatal DRG neuronal cultures derived from neonatal rats. GDNF, NGF, and NT-3 were effective in vitro, while BDNF was not. The range of effects seen in the models described here underscores the importance of testing neuronal responsiveness in more than one model. The biological responsiveness of DRG neurons to GDNF in multiple models suggests that this factor may play a role in the development and maintenance of sensory neurons.
authors.affiliation: Department of Neurobiology, Amgen Inc., Amgen Center, Thousand Oaks, California 91320, USA.
authors.forename: C R
authors.initials: CR
authors.lastname: Matheson
authors.forename: J
authors.initials: J
authors.lastname: Carnahan
authors.forename: J L
authors.initials: JL
authors.lastname: Urich
authors.forename: D
authors.initials: D
authors.lastname: Bocangel
authors.forename: T J
authors.initials: TJ
authors.lastname: Zhang
authors.forename: Q
authors.initials: Q
authors.lastname: Yan
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001345:Autoradiography; D001370:Axonal Transport / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D048429:Cell Size; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D002645:Chickens; D004926:Escherichia coli; D005727:Ganglia, Spinal / Q000166:cytology; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020933:Neurotrophin 3; D011869:Radioligand Assay; D051381:Rats; D012584:Sciatic Nerve / Q000166:cytology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C495039:GDNF protein, human; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D020933:Neurotrophin 3