耳蜗螺旋神经节中小胶质细胞样细胞和卫星胶质细胞标志物的年龄相关变化

文献信息

中文摘要

背景： 年龄相关性听力损失（ARHL）和噪声性听力损失（NIHL）是最常见的获得性听觉损伤形式。然而，这些情况之间的耳蜗免疫微环境是否存在差异，以及它是否可以在治疗上被调节，在很大程度上仍然未知。卫星胶质细胞（SGCs）包裹螺旋神经节（SG）神经元，传统上并未被认为具有免疫能力，并且它们在耳蜗免疫重塑中的作用尚未被研究。方法：使用Iba1、Tmem119、Sox2和CD74的双重免疫荧光染色，在四组中系统地表征了Iba1⁺小胶质细胞样细胞和Sox2⁺ SGCs：年轻对照（CTRL）、年轻NIHL、老年载体处理（Veh）和老年PLX5622处理（PLX）小鼠。结果：在年轻小鼠中，与CTRL相比，NIHL并未显著改变SG中总Iba1⁺细胞密度或Iba1⁺/CD74⁺共表达。相比之下，老年Veh小鼠相对于CTRL显示出总Iba1⁺细胞密度以及Iba1+/Tmem119+、Iba1⁺/CD74⁺和Sox2⁺/CD74⁺细胞密度的显著增加，Sox2⁺/Tmem119⁺细胞也呈现类似的上升趋势，但在多重比较校正后未达到统计学显著性。为期7天的PLX5622疗程显著降低了老年PLX小鼠中总Iba1⁺、Iba1+/Tmem119+、Iba1⁺/CD74⁺和Sox2⁺/CD74⁺细胞密度。结论：这些发现确定了耳蜗SG内免疫和胶质相关标志物阳性细胞密度的年龄相关差异，并表明在PLX5622处理后，选定的标志物阳性细胞群体减少。尽管年龄和基因型存在混杂，且PLX5622可能发挥局部和全身效应，但这些观察结果突显了耳蜗SG免疫微环境作为ARHL进一步研究的潜在领域。

英文摘要

Age-related hearing loss (ARHL) and noise-induced hearing loss (NIHL) are the most prevalent forms of acquired auditory impairment. However, whether the cochlear immune microenvironment differs between these conditions, and whether it can be therapeutically modulated, remains largely unknown. Satellite glial cells (SGCs), which ensheath spiral ganglion (SG) neurons, have not traditionally been considered immune-competent, and their role in cochlear immune remodeling has not been examined. Iba1⁺ microglia-like cells and Sox2⁺ SGCs were systematically characterized across four groups: young control (CTRL), young NIHL, aged vehicle-treated (Veh), and aged PLX5622-treated (PLX) mice, using double immunofluorescence staining for Iba1, Tmem119, Sox2, and CD74. In young mice, NIHL did not significantly alter total Iba1⁺ cell density or Iba1⁺/CD74⁺ co-expression in the SG compared to CTRL. In contrast, aged Veh mice showed a significant increase in total Iba1⁺ cell density and in Iba1+/Tmem119+, Iba1⁺/CD74⁺ and Sox2⁺/CD74⁺ cell densities relative to CTRL, with a similar upward trend for Sox2⁺/Tmem119⁺ cells that did not reach statistical significance after multiple-comparison correction. A 7-day course of the PLX5622 significantly reduced total Iba1⁺, Iba1+/Tmem119+, Iba1⁺/CD74⁺, and Sox2⁺/CD74⁺ cell densities in aged PLX mice. These findings identify age-associated differences in immune- and glia-associated marker-positive cell densities within the cochlear SG and show that selected marker-positive populations were reduced following PLX5622 treatment. Although age and genotype were confounded and PLX5622 may exert both local and systemic effects, these observations highlight the cochlear SG immune microenvironment as a potential area for further investigation in ARHL.