title: Aging after noise exposure: acceleration of cochlear synaptopathy in "recovered" ears.
abstract: Cochlear synaptic loss, rather than hair cell death, is the earliest sign of damage in both noise- and age-related hearing impairment (Kujawa and Liberman, 2009; Sergeyenko et al., 2013). Here, we compare cochlear aging after two types of noise exposure: one producing permanent synaptic damage without hair cell loss and another producing neither synaptopathy nor hair cell loss. Adult mice were exposed (8-16 kHz, 100 or 91 dB SPL for 2 h) and then evaluated from 1 h to ∼ 20 months after exposure. Cochlear function was assessed via distortion product otoacoustic emissions and auditory brainstem responses (ABRs). Cochlear whole mounts and plastic sections were studied to quantify hair cells, cochlear neurons, and the synapses connecting them. The synaptopathic noise (100 dB) caused 35-50 dB threshold shifts at 24 h. By 2 weeks, thresholds had recovered, but synaptic counts and ABR amplitudes at high frequencies were reduced by up to ∼ 45%. As exposed animals aged, synaptopathy was exacerbated compared with controls and spread to lower frequencies. Proportional ganglion cell losses followed. Threshold shifts first appeared >1 year after exposure and, by ∼ 20 months, were up to 18 dB greater in the synaptopathic noise group. Outer hair cell losses were exacerbated in the same time frame (∼ 10% at 32 kHz). In contrast, the 91 dB exposure, producing transient threshold shift without acute synaptopathy, showed no acceleration of synaptic loss or cochlear dysfunction as animals aged, at least to ∼ 1 year after exposure. Therefore, interactions between noise and aging may require an acute synaptopathy, but a single synaptopathic exposure can accelerate cochlear aging.
authors.affiliation: Department of Otology and Laryngology, Harvard Medical School, Boston, Massachusetts 02115, and Eaton-Peabody Laboratories and.
authors.forename: Katharine A
authors.initials: KA
authors.lastname: Fernandez
authors.affiliation: Eaton-Peabody Laboratories and.
authors.forename: Penelope W C
authors.identifier: http://orcid.org/0000-0003-2247-148X
authors.initials: PW
authors.lastname: Jeffers
authors.affiliation: Department of Otology and Laryngology, Harvard Medical School, Boston, Massachusetts 02115, and Eaton-Peabody Laboratories and.
authors.forename: Kumud
authors.initials: K
authors.lastname: Lall
authors.affiliation: Department of Otology and Laryngology, Harvard Medical School, Boston, Massachusetts 02115, and Eaton-Peabody Laboratories and.
authors.forename: M Charles
authors.initials: MC
authors.lastname: Liberman
authors.affiliation: Department of Otology and Laryngology, Harvard Medical School, Boston, Massachusetts 02115, and Eaton-Peabody Laboratories and Department of Audiology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts 02114 sharon_kujawa@meei.harvard.edu.
authors.forename: Sharon G
authors.initials: SG
authors.lastname: Kujawa
mesh_terms: D000161:Acoustic Stimulation; D000375:Aging / Q000502:physiology*; D000429:Alcohol Oxidoreductases; D000818:Animals; D001309:Auditory Threshold; D016923:Cell Death; D056970:Co-Repressor Proteins; D003051:Cochlea / Q000166:cytology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology*; D006198:Hair Cells, Auditory / Q000473:pathology; D006317:Hearing Loss, Noise-Induced / Q000503:physiopathology; D051379:Mice; D008808:Mice, Inbred CBA; D046529:Microscopy, Electron, Transmission; D009622:Noise / Q000009:adverse effects; D017084:Otoacoustic Emissions, Spontaneous / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism; D013136:Spiral Ganglion / Q000473:pathology; D013569:Synapses / Q000473:pathology* / Q000648:ultrastructure; D013997:Time Factors; D014851:Wakefulness / Q000502:physiology
chemical_list: D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D010750:Phosphoproteins; D018091:Receptors, AMPA; D000429:Alcohol Oxidoreductases; C111341:Ctbp2 protein, mouse; C104722:glutamate receptor ionotropic, AMPA 2
keywords: age-related hearing loss; auditory nerve; cochlear neuropathy; cochlear synaptopathy; noise-induced hearing loss; temporary threshold shift