title: Cochlear neuropathy in human presbycusis: Confocal analysis of hidden hearing loss in post-mortem tissue.
abstract: Recent animal work has suggested that cochlear synapses are more vulnerable than hair cells in both noise-induced and age-related hearing loss. This synaptopathy is invisible in conventional histopathological analysis, because cochlear nerve cell bodies in the spiral ganglion survive for years, and synaptic analysis requires special immunostaining or serial-section electron microscopy. Here, we show that the same quadruple-immunostaining protocols that allow synaptic counts, hair cell counts, neuronal counts and differentiation of afferent and efferent fibers in mouse can be applied to human temporal bones, when harvested within 9 h post-mortem and prepared as dissected whole mounts of the sensory epithelium and osseous spiral lamina. Quantitative analysis of five "normal" ears, aged 54-89 yrs, without any history of otologic disease, suggests that cochlear synaptopathy and the degeneration of cochlear nerve peripheral axons, despite a near-normal hair cell population, may be an important component of human presbycusis. Although primary cochlear nerve degeneration is not expected to affect audiometric thresholds, it may be key to problems with hearing in noise that are characteristic of declining hearing abilities in the aging ear.
authors.affiliation: Faculty of Health Sciences, University of Brasilia, Brasilia, Distrito Federal, Brazil.
authors.forename: Lucas M
authors.initials: LM
authors.lastname: Viana
authors.affiliation: Department of Otolaryngology, Massachusetts Eye and Ear, Boston MA, USA.
authors.forename: Jennifer T
authors.initials: JT
authors.lastname: O'Malley
authors.affiliation: Department of Otolaryngology, Massachusetts Eye and Ear, Boston MA, USA.
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Burgess
authors.affiliation: Department of Otolaryngology, Massachusetts Eye and Ear, Boston MA, USA.
authors.forename: Dianne D
authors.initials: DD
authors.lastname: Jones
authors.affiliation: Faculty of Health Sciences, University of Brasilia, Brasilia, Distrito Federal, Brazil.
authors.forename: Carlos A C P
authors.initials: CA
authors.lastname: Oliveira
authors.affiliation: Department of Otology and Laryngology, Harvard Medical School, Boston MA, USA; Department of Otolaryngology, Massachusetts Eye and Ear, Boston MA, USA.
authors.forename: Felipe
authors.initials: F
authors.lastname: Santos
authors.affiliation: Department of Otology and Laryngology, Harvard Medical School, Boston MA, USA; Eaton-Peabody Laboratories, Massachusetts Eye & Ear Infirmary, Boston MA, USA; Department of Otolaryngology, Massachusetts Eye and Ear, Boston MA, USA.
authors.forename: Saumil N
authors.initials: SN
authors.lastname: Merchant
authors.affiliation: Eaton-Peabody Laboratories, Massachusetts Eye & Ear Infirmary, Boston MA, USA; Department of Otolaryngology, Massachusetts Eye and Ear, Boston MA, USA.
authors.forename: Leslie D
authors.initials: LD
authors.lastname: Liberman
authors.affiliation: Department of Otology and Laryngology, Harvard Medical School, Boston MA, USA; Eaton-Peabody Laboratories, Massachusetts Eye & Ear Infirmary, Boston MA, USA; Department of Otolaryngology, Massachusetts Eye and Ear, Boston MA, USA. Electronic address: Charles_Liberman@meei.harvard.edu.
authors.forename: M Charles
authors.initials: MC
authors.lastname: Liberman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001309:Auditory Threshold; D001344:Autopsy; D001369:Axons / Q000473:pathology; D016022:Case-Control Studies; D003051:Cochlea / Q000294:innervation*; D003056:Cochlear Nerve / Q000737:chemistry / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D005455:Fluorescent Antibody Technique; D006198:Hair Cells, Auditory / Q000473:pathology; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009410:Nerve Degeneration; D009622:Noise / Q000009:adverse effects; D010470:Perceptual Masking; D011304:Presbycusis / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D013136:Spiral Ganglion / Q000473:pathology; D013569:Synapses / Q000473:pathology; D013701:Temporal Bone / Q000737:chemistry / Q000473:pathology*