Apical‐to‐basal gradients in age‐related cochlear degeneration and their relationship to “primary” loss of cochlear neurons

Abstract

The predominant conceptual framework for understanding human age-related hearing loss (ARHL, or presbycusis) holds that three different cochlear elements (organ of Corti, afferent neurons, and stria vascularis) can degenerate independently, and exert independent influences on hearing. Within this framework, temporal bones from subjects with ARHL may be classified as exemplifying sensory (referring to organ of Corti), "primary" neural (loss of afferent neurons without loss of their hair cell targets), strial, or mixed ARHL. While there is general agreement as to the types of cochlear cells most affected by aging, there is less agreement about how to classify ARHL, and whether contributions of particular structures to hearing loss can be isolated. The cochlear apex of humans and animals is particularly prone to apparent primary loss of neurons that may represent an aspect of neural ARHL. We recently reported that in 129S6/SvEv mice apical neuronal loss is often accompanied by abnormalities of spiral limbus, pillar cells, and Reissner's membrane (Ohlemiller and Gagnon [2004] J Comp Neurol 469:377-390). We proposed that the initial pathology occurs within limbus, leading to disruption of perilymphatic ion homeostasis, and eventual loss of neurons as one consequence. We have now examined this issue quantitatively in young and old mice of four different strains (129S6/SvEv, CBA/J, C57BL/6, and BALB/c). Abnormalities of apical spiral limbus were found to correlate only weakly with neuronal loss. Strong correlations were found between neuronal loss and abnormalities of both pillar cells and Reissner's membrane, however. Apical neuronal loss and apical-to-basal progression of pathology of limbus, pillar cells, and Reissner's membrane run counter to most reported age-related cochlear trends. Our findings suggest that these changes share a common triggering influence.

Nuclear Factor κB Deficiency Is Associated with Auditory Nerve Degeneration and Increased Noise-Induced Hearing Loss

“…ANOVA, *p Ͻ 0.05, **p Ͻ 0.01. Ohlemiller and Gagnon, 2004). Our results do demonstrate a significant reduction of basal SGNs and OHCs in both WT and p50 Ϫ/Ϫ mice at 8 months of age.…”

Acceleration of Age-Related Hearing Loss by Early Noise Exposure: Evidence of a Misspent Youth

“…Specifically, we show that noise exposure can lead to threshold shifts that progress for years after the exposure and are associated with primary degeneration of the cochlear nerve. This neural etiology contrasts with the noise-induced hair cell (or stereocilia) damage that underlies the initially measured permanent threshold shifts (Liberman and Dodds, 1984) and contrasts with the aging process in unexposed mice, as shown here and by other studies reporting that cochlear neuronal loss is minimal in unexposed mice, even beyond 2 years of age (Lambert and Schwartz, 1982;Willott et al, 1988;Ohlemiller and Gagnon, 2004).…”

A mouse model with postnatal endolymphatic hydrops and hearing loss

“…In these cases, primary neuronal loss is linked to changes in supporting cells and Reissner's membrane. Though hydrops has not been reported in aging mouse models, it has been proposed that the changes in supporting cells and Reissner's membrane may be due to disorders of inner ear fluid homeostasis (Keithley et al, 2004;Ohlemiller and Gagnon, 2004;Willott and Erway, 1998). Due to the presence of hydrops in the young Phex Hyp-Duk /Y mutants (P21-90), one might expect a defect in cochlear fluid balance associated with strial pathology.…”