沙鼠耳蜗出生后发育过程中神经元程序性细胞死亡的时空模式

Stephen M. Echteler , Thomas Magardino , Matthew Rontal
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引用次数: 21

摘要

在出生后早期发育过程中,耳蜗(螺旋)神经节的传入神经元逐渐将其投射细化到听觉毛细胞,因此,在听力开始时,大多数耳蜗神经纤维支配单个听觉受体。一种可能导致耳蜗神经支配变化的机制是螺旋神经节内发育中的神经元的程序性细胞死亡(凋亡)。在本研究中,我们使用TUNEL方法和形态学标准来鉴定蒙古沙鼠出生后第一周内螺旋神经节内的凋亡细胞,当时蒙古沙鼠对耳蜗的传入预测正在积极完善。将单个凋亡的螺旋神经节细胞的位置绘制到沙鼠年龄分级系列的整个神经节的三维重建上,以生成出生后耳蜗凋亡神经节细胞死亡的第一个高分辨率时空图。我们观察到从出生后第4天到第6天螺旋神经节细胞凋亡显著增加。在此期间,最强烈的凋亡活动发生在提供神经支配的螺旋神经节区域耳蜗的下、中、尖匝。本文从沙鼠耳蜗神经支配的产后细化及其可能的听觉功能意义出发,探讨了沙鼠螺旋神经节发育过程中细胞程序性死亡的时间进程和区域变化。
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Spatiotemporal patterns of neuronal programmed cell death during postnatal development of the gerbil cochlea

During early postnatal development, afferent neurons of the cochlear (spiral) ganglion progressively refine their projections to auditory hair cells so that, by hearing onset, most cochlear nerve fibers innervate a single hearing receptor. One mechanism that might contribute to these changes in cochlear innervation is the programmed cell death (apoptosis) of developing neurons within the spiral ganglion. In the present study, we used the TUNEL method and morphological criteria to identify apoptotic cells within the spiral ganglion of the Mongolian gerbil during the first week of postnatal life when afferent projections to the cochlea are actively refined in this species. The locations of individual apoptotic spiral ganglion cells were mapped onto three-dimensional reconstructions of the entire ganglion for an age-graded series of gerbils to produce the first high-resolution, spatiotemporal maps of apoptotic ganglion cell death for the postnatal cochlea. We observed a significant increase in apoptosis in the spiral ganglion from postnatal day (P) 4 through P6. During this time, the most intense apoptotic activity occurred in regions of the spiral ganglion providing innervation to the lower middle and apical turns of the cochlea. The time course and regional variation of programmed cell death within the developing gerbil spiral ganglion are discussed in terms of the postnatal refinement of cochlear innervation and its possible functional significance for hearing in gerbils.

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