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Age‐related changes in the biophysical and morphological characteristics of mouse cochlear outer hair cells
Author(s) -
Jeng JingYi,
Johnson Stuart L.,
Carlton Adam J,
De Tomasi Lara,
Goodyear Richard J.,
De Faveri Francesca,
Furness David N.,
Wells Sara,
Brown Steve D. M.,
Holley Matthew C.,
Richardson Guy P.,
Mustapha Mirna,
Bowl Michael R.,
Marcotti Walter
Publication year - 2020
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jp279795
Subject(s) - ageing , efferent , prestin , cochlea , hearing loss , sensory system , biology , outer hair cells , inner ear , organ of corti , senescence , afferent , neuroscience , microbiology and biotechnology , audiology , medicine , genetics
Key points Age‐related hearing loss (ARHL) is a very heterogeneous disease, resulting from cellular senescence, genetic predisposition and environmental factors (e.g. noise exposure). Currently, we know very little about age‐related changes occurring in the auditory sensory cells, including those associated with the outer hair cells (OHCs). Using different mouse strains, we show that OHCs undergo several morphological and biophysical changes in the ageing cochlea. Ageing OHCs also exhibited the progressive loss of afferent and efferent synapses. We also provide evidence that the size of the mechanoelectrical transducer current is reduced in ageing OHCs, highlighting its possible contribution in cochlear ageing.Abstract Outer hair cells (OHCs) are electromotile sensory receptors that provide sound amplification within the mammalian cochlea. Although OHCs appear susceptible to ageing, the progression of the pathophysiological changes in these cells is still poorly understood. By using mouse strains with a different progression of hearing loss (C57BL/6J, C57BL/6NTac, C57BL/6NTac Cdh23+ , C3H/HeJ), we have identified morphological, physiological and molecular changes in ageing OHCs (9–12 kHz cochlear region). We show that by 6 months of age, OHCs from all strains underwent a reduction in surface area, which was not a sign of degeneration. Although the ageing OHCs retained a normal basolateral membrane protein profile, they showed a reduction in the size of the K + current and non‐linear capacitance, a readout of prestin‐dependent electromotility. Despite these changes, OHCs have a normal V m and retain the ability to amplify sound, as distortion product otoacoustic emission thresholds were not affected in aged, good‐hearing mice (C3H/HeJ, C57BL/6NTac Cdh23+ ). The loss of afferent synapses was present in all strains at 15 months. The number of efferent synapses per OHCs, defined as postsynaptic SK2 puncta, was reduced in aged OHCs of all strains apart from C3H mice. Several of the identified changes occurred in aged OHCs from all mouse strains, thus representing a general trait in the pathophysiological progression of age‐related hearing loss, possibly aimed at preserving functionality. We have also shown that the mechanoelectrical transduction (MET) current from OHCs of mice harbouring the Cdh23 ahl allele is reduced with age, highlighting the possibility that changes in the MET apparatus could play a role in cochlear ageing.