Department of Biology, University of Iowa, Iowa City, Iowa 52242-1324, USA.
Anat Rec (Hoboken). 2012 Nov;295(11):1877-95. doi: 10.1002/ar.22587. Epub 2012 Oct 8.
The spiral ganglion neurons (SGNs) are the afferent neurons of the cochlea, connecting the auditory sensory cells-hair cells-to the brainstem cochlear nuclei. The neurotrophins neurotrophin-3 (NT-3) and brain-derived neurotrophic factor (BDNF) are expressed in the cochlea and both support SGN survival during development. These neurotrophins remain expressed in the postnatal cochlea and continue to play additional roles for SGNs, contributing to maintenance of hair cell-SGN synapses and regulating expression of ion channels, presynaptic and postsynaptic proteins, and SGN membrane electrical properties in a physiologically important spatial pattern. Remarkably, NT-3 and BDNF have different, even opposing, effects on SGN physiology despite the close similarity of their receptors TrkB and TrkC. Recent studies have also raised the possibility that precursor proneurotrophin forms of the neurotrophins play a role in responses to trauma in the cochlea, signaling through the proneurotrophin receptor p75(NTR) . Here, we review expression and function of neurotrophins and their p75(NTR) and Trk-family receptors in the cochlea. We focus, in particular, on neurotrophin functions other than support of SGN survival, including regulation of SGN neurite growth, synaptic and membrane physiology. These functions, unlike survival, are ones for which BDNF and NT-3 substantially differ in their effects. Signal transduction mechanisms of p75(NTR) and of Trk-family receptors are discussed, indicating how these lead to different responses, and we speculate on how BDNF and NT-3 can cause different phenotypic changes in SGNs. Because these complex signaling interactions remain incompletely understood, use of neurotrophins as therapeutic agents in the cochlea should be approached with caution.
螺旋神经节神经元（SGNs）是耳蜗的传入神经元，将听觉感觉细胞——毛细胞——与脑干耳蜗核连接起来。神经营养因子神经营养因子-3（NT-3）和脑源性神经营养因子（BDNF）在耳蜗中表达，两者都支持 SGN 在发育过程中的存活。这些神经营养因子在出生后的耳蜗中继续表达，并继续为 SGN 发挥额外的作用，有助于维持毛细胞-SGN 突触，并调节离子通道、突触前和突触后蛋白的表达，以及 SGN 膜电特性以产生生理上重要的空间模式。值得注意的是，尽管 NT-3 和 BDNF 的受体 TrkB 和 TrkC 非常相似，但它们对 SGN 生理学的影响却不同，甚至相反。最近的研究还提出了一种可能性，即神经营养因子的前神经原形式在耳蜗对创伤的反应中发挥作用，通过前神经原受体 p75（NTR）发出信号。在这里，我们综述了神经营养因子及其 p75（NTR）和 Trk 家族受体在耳蜗中的表达和功能。我们特别关注神经营养因子的除了支持 SGN 存活以外的功能，包括 SGN 神经突生长、突触和膜生理学的调节。与存活不同，BDNF 和 NT-3 在这些功能上的影响有很大的不同。讨论了 p75（NTR）和 Trk 家族受体的信号转导机制，指出了这些机制如何导致不同的反应，我们推测 BDNF 和 NT-3 如何导致 SGN 产生不同的表型变化。由于这些复杂的信号相互作用仍不完全理解，因此在耳蜗中使用神经营养因子作为治疗剂时应谨慎行事。
