Cochlear Synaptic Degeneration and Regeneration After Noise: Effects of Age and Neuronal Subgroup.

Cochlear Synaptic Degeneration and Regeneration After Noise: Effects of Age and Neuronal Subgroup.
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DOI:
10.3389/fncel.2021.684706
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发表时间:
2021
影响因子:
5.3
通讯作者:
Liberman MC
Liberman MC
中科院分区:
医学2区
文献类型:
--
作者:
Hickman TT;Hashimoto K;Liberman LD;Liberman MC

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在CBA/CaJ小鼠中,共聚焦分析表明,声学过度扩张可以立即破坏神经纤维(ANF)与其外周靶点(内毛细胞(IHC))之间的突触,并且多年后,相应数量的ANF细胞体退化。在豚鼠中,暴露后突触前带的消失可能同样引人注目,然而,已报告暴露后恢复至接近基线的计数。由于共焦计数受到阈值问题的混淆,突触带计数的下降和上升可能代表“再生”,即,末端回缩、再延伸和突触发生,或“恢复”,即,突触标记物的下调和随后的上调。为了澄清,我们计数了突触前丝带,评估了它们与突触后受体的并列,测量了ANF末端的延伸,并量化了毛细胞周围这些突触元件的空间组织和尺寸梯度。成年(14个月)暴露豚鼠的当前结果,沿着之前幼年(1个月)暴露豚鼠的结果,表明豚鼠存在暴露后神经再生,但CBA/CaJ小鼠没有,并且这种再生能力延伸到成年。结果还表明,第一次,急性突触损失集中在耳蜗轴侧的IHC,与选择性损失的高阈值ANF低自发率。暴露后的神经突延伸和突触发生之间的形态学相似性,自发地在豚鼠中看到,在CBA/CaJ仅与强迫过度表达的神经营养因子,表明关键的区别可能是在持续的程度或损伤诱导的表达这些信号分子在耳蜗。
In CBA/CaJ mice, confocal analysis has shown that acoustic overexposure can immediately destroy synapses between auditory-nerve fibers (ANFs) and their peripheral targets, the inner hair cells (IHCs), and that years later, a corresponding number of ANF cell bodies degenerate. In guinea pig, post-exposure disappearance of pre-synaptic ribbons can be equally dramatic, however, post-exposure recovery to near-baseline counts has been reported. Since confocal counts are confounded by thresholding issues, the fall and rise of synaptic ribbon counts could represent “regeneration,” i.e., terminal retraction, re-extension and synaptogenesis, or “recovery,” i.e., down- and subsequent up-regulation of synaptic markers. To clarify, we counted pre-synaptic ribbons, assessed their juxtaposition with post-synaptic receptors, measured the extension of ANF terminals, and quantified the spatial organization and size gradients of these synaptic elements around the hair cell. Present results in guinea pigs exposed as adults (14 months), along with prior results in juveniles (1 month), suggest there is post-exposure neural regeneration in the guinea pig, but not the CBA/CaJ mouse, and that this regenerative capacity extends into adulthood. The results also show, for the first time, that the acute synaptic loss is concentrated on the modiolar side of IHCs, consistent with a selective loss of the high-threshold ANFs with low spontaneous rates. The morphological similarities between the post-exposure neurite extension and synaptogenesis, seen spontaneously in the guinea pig, and in CBA/CaJ only with forced overexpression of neurotrophins, suggest that the key difference may be in the degree of sustained or injury-induced expression of these signaling molecules in the cochlea.
DOI: 10.1038/s41598-018-28924-7
发表时间: 2018-07-16
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发表时间: 2011-01-19
期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
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期刊: HEARING RESEARCH
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DOI: 10.1371/journal.pone.0125160
发表时间: 2015
期刊: PloS one
影响因子: 3.7
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