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.
Highlights
The lateral wall of the cochlear duct is formed by the stria vascularis, outer sulcus, spiral prominence and spiral ligament
These cells include marginal, intermediate and basal cells in the stria vascularis, outer sulcus cells including root cells extending into root processes in the spiral ligament, five types (I–V) of fibrocytes in the spiral ligament and various cell types constituting the microvasculature of the cochlear lateral wall
Sox10 protein is expressed in the nuclei of strial marginal and intermediate cells as well as outer sulcus epithelial cells in both young adult and aged CBA/CaJ mice
Summary
The lateral wall of the cochlear duct is formed by the stria vascularis, outer sulcus, spiral prominence and spiral ligament. A variety of lateral wall cell types play critical roles in the maintenance of the high K+ concentration and the positive EP in the scala media [5,7,8] These cells and the ion transport mediators associated with their activity include 1) apical KCNQ1/ KCNE1 channels and basolateral Na/K-ATPase and NKCC exchanger in strial marginal cells [9,10,11]; 2) Kir4.1 channel proteins in strial intermediate and outer sulcus root cells [12,13,14]; and 3) Na/K-ATPase, NKCC exchanger, Kir 5.1 channels, and carbonic anhydrase in fibrocytes of the spiral ligament [15,16,17,18]. A better understanding of the cellular and molecular mechanisms associated with age-related cochlear lateral wall degeneration and declines in regenerative capacity is required to identify potential interventional strategies for the prevention and treatment of presbyacusis [32]
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