Inhibition of repulsive guidance molecule, RGMa, increases afferent synapse formation with auditory hair cells
Inhibition of repulsive guidance molecule, RGMa, increases afferent synapse formation with auditory hair cells
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DOI：
10.1002/dneu.22136
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发表时间：
2014-04-01
影响因子：
3
通讯作者：
Edge, Albert S. B.
中科院分区：
文献类型：
--
作者：
Brugeaud, Aurore;Tong, Mingjie;Edge, Albert S. B.
从听觉神经元延伸到毛细胞的外周纤维对损伤很敏感，用毛细胞替换纤维及其传入突触将是治疗的兴趣。在这里，我们发现RGMa是一种排斥性引导分子，在小鸡视觉系统的发育中发挥作用，在发育中的、新生的和成熟的小鼠内耳中表达。评估了RGMa对传入神经元和毛细胞之间突触发生的影响，从传入连接被移除。通过RGMa阻断抗体处理，神经过程与毛细胞的接触和带状突触部位突触后密度的细化增加，听觉纤维的修剪以实现传入神经元成熟的分支模式加速。因此，RGMa的抑制可以解释为什么听觉神经元再生外周过程的能力较低：出生后的螺旋神经节神经元保留了发出响应突触形成信号的过程的能力，但出生后RGMa的表达似乎不利于传入毛细胞神经支配的再生，并拮抗突触发生。抑制RGMa后突触发生增加表明，引导或抑制因子的操纵可能提供了一种途径来增加脱神经毛细胞中新突触的形成。(c) 2013 Wiley Periodicals, Inc.；中国生物医学工程学报（英文版），2014
The peripheral fibers that extend from auditory neurons to hair cells are sensitive to damage, and replacement of the fibers and their afferent synapse with hair cells would be of therapeutic interest. Here, we show that RGMa, a repulsive guidance molecule previously shown to play a role in the development of the chick visual system, is expressed in the developing, newborn, and mature mouse inner ear. The effect of RGMa on synaptogenesis between afferent neurons and hair cells, from which afferent connections had been removed, was assessed. Contact of neural processes with hair cells and elaboration of postsynaptic densities at sites of the ribbon synapse were increased by treatment with a blocking antibody to RGMa, and pruning of auditory fibers to achieve the mature branching pattern of afferent neurons was accelerated. Inhibition by RGMa could thus explain why auditory neurons have a low capacity to regenerate peripheral processes: postnatal spiral ganglion neurons retain the capacity to send out processes that respond to signals for synapse formation, but expression of RGMa postnatally appears to be detrimental to regeneration of afferent hair cell innervation and antagonizes synaptogenesis. Increased synaptogenesis after inhibition of RGMa suggests that manipulation of guidance or inhibitory factors may provide a route to increase formation of new synapses at deafferented hair cells. (c) 2013 Wiley Periodicals, Inc. Develop Neurobiol 74: 457-466, 2014