Defining responsiveness of avian cochlear neurons to brain-derived neurotrophic factor and nerve growth factor by HSV-1-mediated gene transfer.
The importance of individual members of the neurotrophin gene family for avian inner ear development is not clearly defined. Here we address the role of two neurotrophins, brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), for innervation of the chicken cochlea. We have used defective herpes simplex virus type 1 (HSV-1) vectors, or amplicons, to express these neurotrophins in dissociated cultures of cochlear neurons. HSV-1-mediated expression of BDNF promotes neuronal survival similar to the maximal level seen by exogenously added BDNF and exceeds its potency to produce neurite outgrowth. In contrast, cochlear neurons transduced with an amplicon producing bioactive NGF show no response. These results confirm BDNF as an important mediator of neurotrophin signaling inside avian cochlear neurons. However, these neurons can be rendered NGF-responsive by transducing them with the high-affinity receptor for NGF, TrkA. This study underlines the usefulness of amplicons to study and modify neurotrophin signaling inside neurons.
Garrido
J J
JJ
Universidad de Valladolid y Consejo Superior de Investigaciones Cientificas, Departamento de Bioquímica, Biología Molecular y Fisiología, Facultad de Medicina, Spain.
Alonso
M T
MT
Lim
F
F
Carnicero
E
E
Giraldez
F
F
Schimmang
T
T
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002470:Cell Survival; D002478:Cells, Cultured; D002642:Chick Embryo; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D018259:Herpesvirus 1, Human / Q000235:genetics*; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016501:Neurites / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure / Q000821:virology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis / Q000235:genetics; D013136:Spiral Ganglion / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure / Q000821:virology; D014161:Transduction, Genetic
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D017475:Receptors, Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA