Apical-basal distribution of different subtypes of spiral ganglion neurons in the cochlea and the changes during aging.

Apical-basal distribution of different subtypes of spiral ganglion neurons in the cochlea and the changes during aging.
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耳蜗螺旋神经节神经元不同亚型的顶底分布及衰老过程中的变化。

DOI:
10.1371/journal.pone.0292676
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发表时间:
2023
期刊:
影响因子:
3.7
通讯作者:
--
中科院分区:
综合性期刊3区
文献类型:
--
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声音信息主要通过I型螺旋神经节神经元(SGN)从耳蜗传递到大脑,I型螺旋神经节神经元由具有不同生理特性和选择性表达分子标记的不同亚型组成。目前尚不清楚这些SGN亚型如何沿沿着音调轴分布,以及分布模式是否在衰老过程中发生变化,这可能是年龄相关性听力损失(ARHL)的基础。我们在三个年龄组的CBA/CaJ小鼠中使用免疫组织化学研究了这些问题,包括2-5个月(年轻),17-19个月(中年)和28-32个月(老年)。将小鼠耳蜗冷冻切片并使用抗Tuj 1、钙视网膜蛋白(CR)和钙结合蛋白(CB)的抗体进行三重染色,据报道,这些抗体分别在所有I型、Ia亚型和Ib亚型SGN中表达。根据染色标记物的表达模式将标记的SGN分为四组,包括CR+(Ia亚型)、CB+(Ib亚型)、CR+CB+(Ia/Ib双标记)和CR-CB-(Ic亚型)神经元。这些SGN组的分布进行了分析,在顶部,中部和底部区域的耳蜗。结果表明,Ia、Ib亚型和Ia/Ib双标SGN的检出率在心尖部高,在基底部低。相反,分布模式是相反的,在Ic SGN。这种频率依赖的分布在很大程度上保持在老化过程中,除了优先减少的IC SGN,特别是在基地。这些发现证实了先前基于RNAscope的研究,即SGN亚型在衰老过程中表现出不同的脆弱性。这表明不同频率的声音处理涉及SGN亚型的不同组合,并且基底中Ic SGN的年龄依赖性损失可能特别影响ARHL期间的高频听力。
Sound information is transmitted from the cochlea to the brain mainly by type I spiral ganglion neurons (SGNs), which consist of different subtypes with distinct physiological properties and selective expression of molecular markers. It remains unclear how these SGN subtypes distribute along the tonotopic axis, and whether the distribution pattern changes during aging that might underlie age-related hearing loss (ARHL). We investigated these questions using immunohistochemistry in three age groups of CBA/CaJ mice of either sex, including 2–5 months (young), 17–19 months (middle-age), and 28–32 months (old). Mouse cochleae were cryo-sectioned and triple-stained using antibodies against Tuj1, calretinin (CR) and calbindin (CB), which are reportedly expressed in all type I, subtype Ia, and subtype Ib SGNs, respectively. Labeled SGNs were classified into four groups based on the expression pattern of stained markers, including CR+ (subtype Ia), CB+ (subtype Ib), CR+CB+ (dual-labeled Ia/Ib), and CR-CB- (subtype Ic) neurons. The distribution of these SGN groups was analyzed in the apex, middle, and base regions of the cochleae. It showed that the prevalence of subtype Ia, Ib and dual-labeled Ia/Ib SGNs are high in the apex and low in the base. In contrast, the distribution pattern is reversed in Ic SGNs. Such frequency-dependent distribution is largely maintained during aging except for a preferential reduction of Ic SGNs, especially in the base. These findings corroborate the prior study based on RNAscope that SGN subtypes show differential vulnerability during aging. It suggests that sound processing of different frequencies involves distinct combinations of SGN subtypes, and the age-dependent loss of Ic SGNs in the base may especially impact high-frequency hearing during ARHL.
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