NEUROTROPHIN-4 5 ENHANCES SURVIVAL OF CULTURED SPIRAL GANGLION NEURONS AND PROTECTS THEM FROM CISPLATIN NEUROTOXICITY/

Destruction of spiral ganglion neurons (SGNs) induced by injury and to xins 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 dissociate d cell cultures. The survival-promoting potency of NT-4/5 was equivale nt to that of BDNF and stronger than that of NT-3. In contrast, NGF sh owed no detectable effects. Immunohistochemistry, with TrkB and TrkA a ntisera, revealed that these neurons produced TrkB protein, the functi onal receptor for NT-4/5 and BDNF, but not TrkA protein, the high-affi nity receptor for NGF. The survival-promoting activity of NT-4/5 was c ompletely 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 heari ng impairment caused by damage to primary auditory afferent neurons.