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Journal of Neuroscience, Vol 15, 5079-5087, Copyright © 1995 by Society for Neuroscience
Neurotrophin-4/5 enhances survival of cultured spiral ganglion neurons and protects them from cisplatin neurotoxicity
JL Zheng, RR Stewart and WQ Gao
Department of Neuroscience, Genentech, Inc., South San Francisco, California 94080, USA.
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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