Brain-Derived Neurotrophic Factor and Glial Cell Line-Derived Neurotrophic Factor Are Required Simultaneously for Survival of Dopaminergic Primary Sensory Neurons In Vivo

• Published in: The Journal of neuroscience 2001-01, Vol.21 (2), p.581-589
• Main Authors: Erickson, Jeffery T, Brosenitsch, Teresa A, Katz, David M
• Format: Article
• Language: English
• Subjects: Animals; Brain-Derived Neurotrophic Factor - genetics; Brain-Derived Neurotrophic Factor - metabolism; Brain-Derived Neurotrophic Factor - pharmacology; Carotid Body - physiology; Cell Count; Cell Survival - drug effects; Cells, Cultured; Dopamine - metabolism; Drosophila Proteins; Glial Cell Line-Derived Neurotrophic Factor; Glial Cell Line-Derived Neurotrophic Factor Receptors; Immunohistochemistry; Mice; Mice, Knockout; Nerve Growth Factors; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Nerve Tissue Proteins - pharmacology; Neurons, Afferent - cytology; Neurons, Afferent - drug effects; Neurons, Afferent - metabolism; nodose ganglion; Nodose Ganglion - cytology; Nodose Ganglion - drug effects; Nodose Ganglion - metabolism; Organ Specificity; petrosal ganglion; Plethysmography; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-ret; Rats; Receptor Protein-Tyrosine Kinases - metabolism; Respiration - genetics; Tyrosine 3-Monooxygenase - metabolism
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/jneurosci.21-02-00581.2001

Null mutations affecting members of the transforming growth factor-beta and neurotrophin families result in overlapping patterns of neuronal cell death. This is particularly striking in the cranial sensory nodose-petrosal ganglion complex (NPG), in which loss of either glial cell line-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), or neurotrophin-4 (NT-4) results in a 30-50% reduction in neuronal survival. It is unknown, however, whether GDNF and any single neurotrophin support survival of the same cells, and if so, whether they are required simultaneously or sequentially during development. To approach these issues we defined survival requirements of nodose and petrosal neurons for GDNF in vitro and in bdnf, gdnf, and bdnf/gdnf null mutant mice, as well as the distribution of GDNF in NPG target tissues. Our analyses focused on the total population of ganglion cells as well as the subset of NPG neurons that are dopaminergic. Neuron losses in bdnf/gdnf double mutants are not additive of the losses in single bdnf or gdnf null mutants, indicating that many cells, including dopaminergic neurons, require both GDNF and BDNF for survival in vivo. Moreover, both factors are required during the same period of development, between embryonic day (E) 15.5 and E17.5. In addition, GDNF, like BDNF is expressed in target tissues at the time of initial target innervation and coincident with GDNF dependence of the innervating neurons. Together, these findings demonstrate that both GDNF and BDNF can act as target-derived trophic factors and are required simultaneously for survival of some primary sensory neurons.