Functional role of neurotrophin-3 in synapse regeneration by spiral ganglion neurons on inner hair cells after excitotoxic trauma in vitro.
Functional role of neurotrophin-3 in synapse regeneration by spiral ganglion neurons on inner hair cells after excitotoxic trauma in vitro.
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DOI：
10.1523/jneurosci.1434-10.2011
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发表时间：
2011-05-25
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影响因子：
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通讯作者：
Green SH
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文献类型：
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作者：
Wang Q;Green SH
螺旋神经节神经元 (SGN) 位于毛细胞的突触后并投射到脑干。 SGN 突触的内毛细胞 (IHC) 容易受到谷氨酸兴奋性毒性和声损伤的影响，对 SGN 的长期存活可能产生不利后果。我们使用来自 P6 幼鼠的耳蜗外植体培养物（由与螺旋神经节的相应部分保持完整的 Corti 器官的一部分组成）来研究体外 IHC-SGN 突触的兴奋性毒性损伤。正常的神经支配模式在体外得以保留。用 NMDA 和红藻氨酸进行短暂治疗会导致 IHC-SGN 突触丧失和远端 1 型 SGN 外周轴突变性，类似于体内兴奋性毒性或噪音引起的 SGN 外周轴突损伤。 IHC 突触前带的数量没有显着改变。 IHC 发生神经支配，并且再生轴突仍局限于 IHC 行。然而，突触后密度 (PSD) 的数量并未完全恢复，并且并非所有轴突都重新生长到 IHC。添加 NT-3 或 BDNF 会增加轴突生长和突触发生。用 TrkC-IgG 选择性阻断内源性 NT-3 信号传导会减少轴突和 PSD 的再生，但阻断 BDNF 的 TrkB-IgG 没有这种作用，表明内源性 NT-3 对于 SGN 轴突生长和突触发生是必需的。值得注意的是，即使在 BDNF 存在的情况下，TrkC-IgG 也会减少轴突生长和突触发生，这表明内源性 NT-3 在促进 Corti 器官中的 SGN 轴突生长和 IHC 上的突触发生方面具有 BDNF 无法模仿的独特作用。
Spiral ganglion neurons (SGNs) are postsynaptic to hair cells and project to the brainstem. The inner hair cell (IHC) to SGN synapse is susceptible to glutamate excitotoxicity and to acoustic trauma, with potentially adverse consequences to long-term SGN survival. We used a cochlear explant culture from P6 rat pups consisting of a portion of organ of Corti maintained intact with the corresponding portion of spiral ganglion to investigate excitotoxic damage to IHC-SGN synapses in vitro. The normal innervation pattern is preserved in vitro. Brief treatment with NMDA and kainate results in loss of IHC–SGN synapses and degeneration of the distal type 1 SGN peripheral axons, mimicking damage to SGN peripheral axons caused by excitotoxicity or noise in vivo. The number of IHC presynaptic ribbons is not significantly altered. Reinnervation of IHCs occurs and regenerating axons remain restricted to the IHC row. However, the number of postsynaptic densities (PSDs) does not fully recover and not all axons regrow to the IHCs. Addition of either NT-3 or BDNF increases axon growth and synaptogenesis. Selective blockade of endogenous NT-3 signaling with TrkC-IgG reduced regeneration of axons and PSDs, but TrkB-IgG, which blocks BDNF, has no such effect, indicating that endogenous NT-3 is necessary for SGN axon growth and synaptogenesis. Remarkably, TrkC-IgG reduced axon growth and synaptogenesis even in the presence of BDNF, indicating that endogenous NT-3 has a distinctive role, not mimicked by BDNF, in promoting SGN axon growth in the organ of Corti and synaptogenesis on IHCs.