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Survival of adult spiral ganglion neurons requires erbB receptor signaling in the inner ear.
- Source :
-
The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2004 Oct 06; Vol. 24 (40), pp. 8651-61. - Publication Year :
- 2004
-
Abstract
- Degeneration of cochlear sensory neurons is an important cause of hearing loss, but the mechanisms that maintain the survival of adult cochlear sensory neurons are not clearly defined. We now provide evidence implicating the neuregulin (NRG)-erbB receptor signaling pathway in this process. We found that NRG1 is expressed by spiral ganglion neurons (SGNs), whereas erbB2 and erbB3 are expressed by supporting cells of the organ of Corti, suggesting that these molecules mediate interactions between these cells. Transgenic mice in which erbB signaling in adult supporting cells is disrupted by expression of a dominant-negative erbB receptor show severe hearing loss and 80% postnatal loss of type-I SGNs without concomitant loss of the sensory cells that they contact. Quantitative RT-PCR analysis of neurotrophic factor expression shows a specific downregulation in expression of neurotrophin-3 (NT3) in the transgenic cochleas before the onset of neuronal death. Because NT3 is critical for survival of type I SGNs during development, these results suggest that it plays similar roles in the adult. Together, the data indicate that adult cochlear supporting cells provide critical trophic support to the neurons, that survival of postnatal cochlear sensory neurons depends on reciprocal interactions between neurons and supporting cells, and that these interactions are mediated by NRG and neurotrophins.
- Subjects :
- Animals
Cell Survival
Cochlea growth & development
Cochlea metabolism
Down-Regulation
ErbB Receptors genetics
ErbB Receptors metabolism
Glial Fibrillary Acidic Protein genetics
Hair Cells, Auditory cytology
Hair Cells, Auditory growth & development
Hair Cells, Auditory metabolism
Hearing Loss etiology
Hearing Loss pathology
Labyrinth Supporting Cells metabolism
Mice
Mice, Transgenic
Mutation
Nerve Tissue Proteins metabolism
Neuregulin-1
Neurons, Afferent cytology
Neurotrophin 3 genetics
Promoter Regions, Genetic
Receptor, ErbB-4
Signal Transduction
Spiral Ganglion growth & development
Spiral Ganglion metabolism
Cochlea innervation
ErbB Receptors physiology
Neurons, Afferent metabolism
Neurotrophin 3 metabolism
Spiral Ganglion cytology
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2401
- Volume :
- 24
- Issue :
- 40
- Database :
- MEDLINE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 15470130
- Full Text :
- https://doi.org/10.1523/JNEUROSCI.0733-04.2004