Neurotrophin-4/5 enhances survival of cultured spiral ganglion neurons and protects them from cisplatin neurotoxicity
| Autor: | J. L. Zheng, R. R. Stewart, Wei-Qiang Gao |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 1995 |
| Předmět: |
Cell Survival
Recombinant Fusion Proteins Nerve Tissue Proteins Tropomyosin receptor kinase B Neurotrophin-3 Receptors Nerve Growth Factor Tropomyosin receptor kinase A Neurotrophin 3 medicine otorhinolaryngologic diseases Low-affinity nerve growth factor receptor Animals Nerve Growth Factors Rats Wistar Receptor Ciliary Neurotrophic Factor Spiral ganglion Cells Cultured Brain-derived neurotrophic factor Neurons biology General Neuroscience Brain-Derived Neurotrophic Factor Articles Cell biology Rats medicine.anatomical_structure Nerve growth factor Neuroprotective Agents nervous system Immunoglobulin G biology.protein Cisplatin Spiral Ganglion Neuroscience Neurotrophin |
| Popis: | Destruction of spiral ganglion neurons (SGNs) induced by injury and toxins is one of the major causes for hearing loss. Here we report that neurotrophin-4/5 (NT-4/5), a member of the nerve growth factor family, promoted survival of postnatal rat SGNs up to threefold in dissociated cell cultures. The survival-promoting potency of NT-4/5 was equivalent to that of BDNF and stronger than that of NT-3. In contrast, NGF showed no detectable effects. Immunohistochemistry, with TrkB and TrkA antisera, revealed that these neurons produced TrkB protein, the functional receptor for NT-4/5 and BDNF, but not TrkA protein, the high- affinity receptor for NGF. The survival-promoting activity of NT-4/5 was completely inhibited by TrkB-IgG fusion protein. These results suggest that NT-4/5 is a specific survival factor for SGNs. In addition, NT-4/5 protected the SGNs from neurotoxic effects of the anti- cancer drug, cisplatin. Thus, NT-4/5 may have therapeutic value in preventing hearing impairment caused by damage to primary auditory afferent neurons. |
| Databáze: | OpenAIRE |
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