Sox10 Expressing Cells in the Lateral Wall of the Aged Mouse and Human Cochlea

Abstract

Age-related hearing loss (presbycusis) is a common human disorder, affecting one in three Americans aged 60 and over. Previous studies have shown that presbyacusis is associated with a loss of non-sensory cells in the cochlear lateral wall. Sox10 is a transcription factor crucial to the development and maintenance of neural crest-derived cells including some non-sensory cell types in the cochlea. Mutations of the Sox10 gene are known to cause various combinations of hearing loss and pigmentation defects in humans. This study investigated the potential relationship between Sox10 gene expression and pathological changes in the cochlear lateral wall of aged CBA/CaJ mice and human temporal bones from older donors. Cochlear tissues prepared from young adult (1–3 month-old) and aged (2–2.5 year-old) mice, and human temporal bone donors were examined using quantitative immunohistochemical analysis and transmission electron microscopy. Cells expressing Sox10 were present in the stria vascularis, outer sulcus and spiral prominence in mouse and human cochleas. The Sox10+ cell types included marginal and intermediate cells and outer sulcus cells, including those that border the scala media and those extending into root processes (root cells) in the spiral ligament. Quantitative analysis of immunostaining revealed a significant decrease in the number of Sox10+ marginal cells and outer sulcus cells in aged mice. Electron microscopic evaluation revealed degenerative alterations in the surviving Sox10+ cells in aged mice. Strial marginal cells in human cochleas from donors aged 87 and older showed only weak immunostaining for Sox10. Decreases in Sox10 expression levels and a loss of Sox10+ cells in both mouse and human aged ears suggests an important role of Sox10 in the maintenance of structural and functional integrity of the lateral wall. A loss of Sox10+ cells may also be associated with a decline in the repair capabilities of non-sensory cells in the aged ear.

Single Cell and Single Nucleus RNA-Seq Reveal Cellular Heterogeneity and Homeostatic Regulatory Networks in Adult Mouse Stria Vascularis

“…Whether other cell types in the SV derive from neural crest cells remains to be determined by further lineage tracing experiments and have not been shown in more recent lineage tracing experiments (Shibata et al, 2016). The contribution of neurocristopathies to hearing loss is a developing area of research (Hao et al, 2014;Locher et al, 2015;Shibata et al, 2016;Ritter and Martin, 2019). Another example of hearing loss where multiple cell types may be affected includes Connexin 26 and 30 encoded by Gjb2 and Gjb6, respectively, which appear to be expressed in intermediate and basal cells and, to a lesser extent, marginal cells ( Figure 10) (Lang et al, 2007;Nickel and Forge, 2008;Liu et al, 2009;Mei et al, 2017).…”

Pathology and mechanisms of cochlear aging

“…Quiet‐aged gerbil, rat, and beagle dog cochleas have strial and spiral ligament degeneration at both ends of the cochlear duct related to vascular degeneration in the same locations (Gratton et al, ,; Keithley, Ryan, & Feldman, ; Le & Keithley, ; Spicer & Schulte, ). Sox10 , a transcription factor involved in the development and maintenance of cells derived from the neural crest, is reduced in cells of the stria vascularis and spiral ligament in aged CBA/CaJ mouse cochleas, as well as human temporal bones (Hao et al, ).…”

QTL Mapping of Endocochlear Potential Differences between C57BL/6J and BALB/cJ mice

“…Colored traces and Y axes have same meaning as in Figure 4. cells, including strial intermediate cells (Watanabe et al 2000), and has been implicated in how aging affects the stria (Hao et al 2014). Kcnj4 encodes a K + channel, although with no established role in lateral wall function (Alsaber et al 2006).…”