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  • Title: Neurotrophin-4/5 enhances survival of cultured spiral ganglion neurons and protects them from cisplatin neurotoxicity.
    Author: Zheng JL, Stewart RR, Gao WQ.
    Journal: J Neurosci; 1995 Jul; 15(7 Pt 2):5079-87. PubMed ID: 7623136.
    Abstract:
    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.
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