Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina, United States of America.
PLoS One. 2012;7(4):e34500. doi: 10.1371/journal.pone.0034500. Epub 2012 Apr 5.
Age-related hearing loss (presbyacusis) is the most common type of hearing impairment. One of the most consistent pathological changes seen in presbyacusis is the loss of spiral ganglion neurons (SGNs). Defining the cellular and molecular basis of SGN degeneration in the human inner ear is critical to gaining a better understanding of the pathophysiology of presbyacusis. However, information on age-related cellular and molecular alterations in the human spiral ganglion remains scant, owing to the very limited availably of human specimens suitable for high resolution morphological and molecular analysis. This study aimed at defining age-related alterations in the auditory nerve in human temporal bones and determining if immunostaining for myelin basic protein (MBP) can be used as an alternative approach to electron microscopy for evaluating myelin degeneration. For comparative purposes, we evaluated ultrastructural alternations and changes in MBP immunostaining in aging CBA/CaJ mice. We then examined 13 temporal bones from 10 human donors, including 4 adults aged 38-46 years (middle-aged group) and 6 adults aged 63-91 years (older group). Similar to the mouse, intense immunostaining of MBP was present throughout the auditory nerve of the middle-aged human donors. Significant declines in MBP immunoreactivity and losses of MBP(+) auditory nerve fibers were observed in the spiral ganglia of both the older human and aged mouse ears. This study demonstrates that immunostaining for MBP in combination with confocal microscopy provides a sensitive, reliable, and efficient method for assessing alterations of myelin sheaths in the auditory nerve. The results also suggest that myelin degeneration may play a critical role in the SGN loss and the subsequent decline of the auditory nerve function in presbyacusis.
年龄相关性听力损失（老年性聋）是最常见的听力障碍类型。老年性聋最一致的病理学改变之一是螺旋神经节神经元（SGN）的丧失。明确人类内耳中 SGN 变性的细胞和分子基础对于更好地理解老年性聋的病理生理学至关重要。然而，由于适合高分辨率形态学和分子分析的人类标本非常有限，因此有关人类螺旋神经节与年龄相关的细胞和分子改变的信息仍然很少。本研究旨在定义人类颞骨听神经的年龄相关性改变，并确定髓鞘碱性蛋白（MBP）免疫染色是否可以替代电子显微镜用于评估髓鞘变性。为了进行比较，我们评估了衰老 CBA/CaJ 小鼠中超微结构改变和 MBP 免疫染色的变化。然后，我们检查了来自 10 名供体的 13 个颞骨，其中包括 4 名年龄在 38-46 岁的成年人（中年组）和 6 名年龄在 63-91 岁的成年人（老年组）。与小鼠相似，中年人类供体的整个听神经中都存在强烈的 MBP 免疫染色。在老年人类和衰老小鼠耳朵的螺旋神经节中，均观察到 MBP 免疫反应性显著下降和 MBP（+）听神经纤维丢失。这项研究表明，MBP 免疫染色结合共聚焦显微镜提供了一种敏感、可靠和高效的方法来评估听神经髓鞘的改变。研究结果还表明，髓鞘变性可能在 SGN 丧失和老年性聋中听神经功能随后下降中起关键作用。
