Department of Anatomy, All India Institute of Medical Sciences, New Delhi, 110029, India.
Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, 110029, India.
Hear Res. 2020 Mar 15;388:107883. doi: 10.1016/j.heares.2020.107883. Epub 2020 Jan 8.
Animal-studies associate age-related hearing loss (presbycusis) with decreasing number of spiral ganglion neurons (SGNs) in Rosenthal's canal (RC) of cochlea. The excitatory neurotransmitter for SGNs is glutamate (through its receptor NMDAR 2B), which can be neurotoxic through Ca overload. Neurotoxicity is balanced by calcium-binding proteins (CBPs) like Parvalbumin (PV), which is the predominant CBP of the SGNs. To estimate the volume of the RC and total number of SGNs that are immunoreactive to PV and NMDAR 2B, we used unbiased stereology in 35 human cochleae derived from cadavers of persons from 2nd to 8th decade of life (subsequently statistically divided into two groups) and compared them to the total number of cresyl violet (CV) stained SGNs. We also estimated the volume of individual neurons and their nuclei. Regression analysis was made on estimated parameters against age. Hierarchical-cluster analysis was done on the neuronal against neuronal nuclear volumes.The average volume of the RC did not change with increasing age (p = 0.4115). The total number of SGNs (CV-stained and those separately expressing PV and NMDAR 2B) significantly decreased with age (p < 0.001). We identified three distinct populations of neurons on the basis of their volumes among SGNs. Thus, there is significant age-related decline in the total number of SGNs, which starts early in life. It may be due to ambient noise and inadequate neutralisation of excitotoxicity.
动物研究将与年龄相关的听力损失（presbycusis）与罗斯滕塔尔氏管（RC）中螺旋神经节神经元（SGN）数量的减少联系起来。SGN 的兴奋性神经递质是谷氨酸（通过其受体 NMDAR 2B），它可以通过 Ca 过载产生神经毒性。神经毒性通过钙结合蛋白（CBPs）如 Parvalbumin（PV）来平衡，PV 是 SGN 的主要 CBP。为了估计 RC 的体积和对 PV 和 NMDAR 2B 免疫反应性的 SGN 总数，我们在 35 个人尸检耳蜗中使用无偏立体学方法，这些耳蜗来自 20 至 80 岁的人（随后在统计学上分为两组），并将其与 Cresyl Violet（CV）染色的 SGN 总数进行比较。我们还估计了单个神经元及其核的体积。对估计的参数与年龄进行回归分析。对神经元与神经元核体积进行层次聚类分析。RC 的平均体积随年龄增加而没有变化（p=0.4115）。CV 染色的 SGN 总数（以及分别表达 PV 和 NMDAR 2B 的 SGN）随年龄显著减少（p<0.001）。我们根据 SGN 中神经元的体积将其分为三个不同的群体。因此，SGN 的总数与年龄相关的显著下降，这种下降早在生命早期就开始了。这可能是由于环境噪声和兴奋性毒性的中和不足。
