Hurley Patricia A, Crook Jeremy M, Shepherd Robert K
Department of Otolaryngology, University of Melbourne, Australia.
Eur J Neurosci. 2007 Oct;26(7):1813-21. doi: 10.1111/j.1460-9568.2007.05811.x. Epub 2007 Sep 14.
Loss of sensory hair cells within the cochlea results in a permanent sensorineural hearing loss and initiates the gradual degeneration of spiral ganglion neurons (SGNs) - the primary afferent neurons of the cochlea. While these neurons are normally myelinated via Schwann cells, loss of myelin occurs as a precursor to neural degeneration. However, the relationship between demyelination and the status of Schwann cells in deafness is not well understood. We used a marker of peripheral myelin (myelin protein zero; P0) and a marker of Schwann cells (S100) to determine the temporal sequence of myelin and Schwann cell loss as a function of duration of deafness. Rat pups were systemically deafened for periods ranging from 2 weeks to greater than 6 months by co-administration of frusemide and gentamicin. Cochleae were cryosectioned and quantitative immunohistochemistry used to determine the extent of P0 and S100 labelling within the peripheral processes, SGN soma and their central processes within the modiolus. SGN density was also determined for each cochlear turn. P0 labelling decreased throughout the cochlea with increasing duration of deafness. The reduction in P0 labelling occurred at a faster rate than the SGN loss. In contrast, S100 labelling was not significantly reduced compared with age-matched controls in any cochlear region until 6 months post-deafening. These results suggest that Schwann cells may revert to non-myelinating phenotypes in response to deafness and exhibit greater survival traits than SGNs. The potential clinical significance of these findings for cochlear implants is discussed.
耳蜗内感觉毛细胞的丧失会导致永久性感音神经性听力损失，并引发螺旋神经节神经元（SGNs）——耳蜗的初级传入神经元——的逐渐退化。虽然这些神经元通常通过施万细胞进行髓鞘化，但髓鞘丧失是神经退化的先兆。然而，耳聋中脱髓鞘与施万细胞状态之间的关系尚未得到充分理解。我们使用外周髓鞘标记物（髓鞘蛋白零；P0）和施万细胞标记物（S100）来确定髓鞘和施万细胞丧失的时间顺序，作为耳聋持续时间的函数。通过联合给予速尿和庆大霉素，将新生大鼠系统性致聋2周以上至6个月以上。对耳蜗进行冰冻切片，并使用定量免疫组织化学来确定外周突、SGN胞体及其在内侧耳蜗管内的中枢突中P0和S100标记的程度。还确定了每个耳蜗螺旋的SGN密度。随着耳聋持续时间的增加，整个耳蜗的P0标记减少。P0标记的减少速度比SGN的丧失速度更快。相比之下，直到致聋后6个月，与年龄匹配的对照组相比，任何耳蜗区域的S100标记都没有显著减少。这些结果表明，施万细胞可能会因耳聋而恢复为非髓鞘化表型，并表现出比SGN更强的存活特性。本文讨论了这些发现对人工耳蜗的潜在临床意义。
