神经营养因子-4/5可提高培养的螺旋神经节神经元的存活率，并保护其免受顺铂神经毒性的影响。
Neurotrophin-4/5 enhances survival of cultured spiral ganglion neurons and protects them from cisplatin neurotoxicity.
作者信息
Zheng J L, Stewart R R, Gao W Q
机构信息
Department of Neuroscience, Genentech, Inc., South San Francisco, California 94080, USA.
出版信息
J Neurosci. 1995 Jul;15(7 Pt 2):5079-87. doi: 10.1523/JNEUROSCI.15-07-05079.1995.
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.
由损伤和毒素诱导的螺旋神经节神经元（SGNs）破坏是听力丧失的主要原因之一。在此我们报告，神经营养因子-4/5（NT-4/5）作为神经生长因子家族的一员，在离体细胞培养中可使新生大鼠SGNs的存活率提高达三倍。NT-4/5的促存活效力与脑源性神经营养因子（BDNF）相当，且强于神经营养因子-3（NT-3）。相比之下，神经生长因子（NGF）未显示出可检测到的作用。用TrkB和TrkA抗血清进行的免疫组织化学显示，这些神经元产生TrkB蛋白，即NT-4/5和BDNF的功能性受体，但不产生TrkA蛋白，即NGF 的高亲和力受体。NT-4/5的促存活活性被TrkB-IgG融合蛋白完全抑制。这些结果表明，NT-4/5是SGNs的特异性存活因子。此外，NT-4/5保护SGNs免受抗癌药物顺铂的神经毒性作用。因此，NT-4/5在预防由初级听觉传入神经元损伤引起的听力障碍方面可能具有治疗价值。
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