PMID- 8568514 OWN - NLM STAT- MEDLINE DCOM- 19960307 LR - 20161123 IS - 0022-3034 (Print) IS - 0022-3034 (Linking) VI - 28 IP - 3 DP - 1995 Nov TI - Neurotrophin-4/5, brain-derived neurotrophic factor, and neurotrophin-3 promote survival of cultured vestibular ganglion neurons and protect them against neurotoxicity of ototoxins. PG - 330-40 AB - The ability of neurotrophin-4/5 (NT-4/5), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and nerve growth factor (NGF) to promote survival of postnatal rat vestibular ganglion neurons (VGNs) was examined in dissociated cell cultures. Of the four neurotrophins, NT-4/5 and BDNF were equally effective but more potent than NT-3 in promoting the survival of VGNs. In contrast, NGF showed no detectable effects. As expected, TrkB-IgG (a fusion protein of extracellular domain of TrkB and Fc domain of human immunoglobulin G) specifically inhibited the survival-promoting, effects by NT-4/5 or BDNF and TrkC-IgG fusion protein completely blocked that of NT-3. Immunohistochemistry with TrkB, TrkA, and p75 antisera revealed that VGNs made TrkB and p75 proteins, but not TrkA protein. Ototoxic therapeutic drugs such as cisplatin and gentamicin often induce degeneration of hair cells and ganglion neurons in both auditory and vestibular systems that leads to impairment of hearing and balance. When cisplatin and gentamicin were added to the dissociated VGN culture in which the hair cells were absent, additional cell death of VGNs was induced, suggesting that the two ototoxins may have a direct neurotoxic effect on ganglion neurons in addition to their known toxicity on hair cells. However, if the cultures were co-treated with neurotrophins, NT-4/5, BDNF, and NT-3, but not NGF, prevented or reduced the neurotoxicity of the two ototoxins. Thus, the three neurotrophins are survival factors for VGNs and are implicated in the therapeutic prevention of VGN loss caused by injury and ototoxins. FAU - Zheng, J L AU - Zheng JL AD - Department of Neuroscience, Genentech, Inc., South San Francisco, California 94080, USA. FAU - Stewart, R R AU - Stewart RR FAU - Gao, W Q AU - Gao WQ LA - eng PT - Journal Article PL - United States TA - J Neurobiol JT - Journal of neurobiology JID - 0213640 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Gentamicins) RN - 0 (Nerve Growth Factors) RN - 0 (Nerve Tissue Proteins) RN - 0 (Neuroprotective Agents) RN - 0 (Neurotrophin 3) RN - 145172-44-7 (neurotrophin 5) RN - P658DCA9XD (neurotrophin 4) RN - Q20Q21Q62J (Cisplatin) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor MH - Cell Survival/drug effects MH - Cells, Cultured MH - Cisplatin/toxicity MH - Ganglia/cytology/*drug effects MH - Gentamicins/toxicity MH - Humans MH - Nerve Growth Factors/*pharmacology MH - Nerve Tissue Proteins/pharmacology MH - Neurons/*drug effects MH - Neuroprotective Agents/*pharmacology MH - Neurotrophin 3 MH - Rats MH - Rats, Wistar MH - Vestibule, Labyrinth/cytology/*drug effects EDAT- 1995/11/01 00:00 MHDA- 1995/11/01 00:01 CRDT- 1995/11/01 00:00 PHST- 1995/11/01 00:00 [pubmed] PHST- 1995/11/01 00:01 [medline] PHST- 1995/11/01 00:00 [entrez] AID - 10.1002/neu.480280306 [doi] PST - ppublish SO - J Neurobiol. 1995 Nov;28(3):330-40. doi: 10.1002/neu.480280306.