Opposing expression gradients of calcitonin-related polypeptide alpha (Calca/Cgrpα) and tyrosine hydroxylase (Th) in type II afferent neurons of the mouse cochlea.
Opposing expression gradients of calcitonin-related polypeptide alpha (Calca/Cgrpα) and tyrosine hydroxylase (Th) in type II afferent neurons of the mouse cochlea.
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DOI：
10.1002/cne.24341
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发表时间：
2018-02-15
期刊：
影响因子：
--
通讯作者：
Fuchs PA
中科院分区：
文献类型：
--
作者：
Wu JS;Vyas P;Glowatzki E;Fuchs PA
II型螺旋神经节神经元（SGN）是小口径的无髓鞘传入神经，其沿着耳蜗螺旋延伸数百微米的树突状乔木，接触许多外毛细胞（OHC）。尽管有这么多的接触，II型传入神经对声音不敏感，并且仅通过OHC释放的谷氨酸进行弱去极化。最近的研究表明，II型传入可能是耳蜗伤害性感受器，并且可以被组织损伤期间释放的ATP兴奋，类似于躯体疼痛感测C纤维。目前的工作比较了在C纤维中发现的两种基因在耳蜗II型传入中的表达模式：降钙素相关多肽α（Calca/Cgrpα），特异于疼痛感受C纤维，酪氨酸羟化酶（Th），特异于低阈值机械感受C纤维，这是以前被证明是II型与I型耳蜗传入的选择性生物标志物。3周龄至2月龄CGRPα-EGFP（GENSAT）小鼠的整体耳蜗制备物显示，在SGN亚组中表达Cgrpα，II型样外周树突延伸至OHC下方。与其他分子标记物的双标记证实标记的SGN既不是I型SGN，也不是橄榄耳蜗传出神经。Cgrpα在听力发作前开始在II型SGN中表达，但在成人中表达水平下降。Cgrpα和Th的表达模式形成相反的梯度，Th优先表达于顶侧II型传入神经元，Cgrpα优先表达于基底侧II型传入神经元，表明II型传入神经元之间存在异质性。Th和Cgrpα在耳蜗中回的表达并不排斥，也有共同表达，且在耳蜗中回表达最丰富。
Type II spiral ganglion neurons (SGNs) are small caliber, unmyelinated afferents that extend dendritic arbors hundreds of microns along the cochlear spiral, contacting many outer hair cells (OHCs). Despite these many contacts, type II afferents are insensitive to sound and only weakly depolarized by glutamate release from OHCs. Recent studies suggest that type II afferents may be cochlear nociceptors, and can be excited by ATP released during tissue damage, by analogy to somatic pain-sensing C-fibers. The present work compares the expression patterns among cochlear type II afferents of two genes found in C-fibers: calcitonin-related polypeptide alpha (Calca/Cgrpα), specific to pain-sensing C-fibers, and tyrosine hydroxylase (Th), specific to low-threshold mechanoreceptive C-fibers, which was shown previously to be a selective biomarker of type II versus type I cochlear afferents. Whole-mount cochlear preparations from 3-week to 2-month-old CGRPα-EGFP (GENSAT) mice showed expression of Cgrpα in a subset of SGNs with type II-like peripheral dendrites extending beneath OHCs. Double labeling with other molecular markers confirmed that the labeled SGNs were neither type I SGNs nor olivocochlear efferents. Cgrpα starts to express in type II SGNs before hearing onset, but the expression level declines in the adult. The expression patterns of Cgrpα and Th formed opposing gradients, with Th being preferentially expressed in apical and Cgrpα in basal type II afferent neurons, indicating heterogeneity among type II afferent neurons. The expression of Th and Cgrpα was not mutually exclusive and co-expression could be observed, most abundantly in the middle cochlear turn.
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