Hidden hearing loss and endbulbs of Held: Evidence for central pathology before detection of ABR threshold increases

Muniak, Michael A.; Ayeni, Femi E.; Ryugo, David K.

doi:10.1016/j.heares.2018.03.021

Cited by 36 publications

(22 citation statements)

References 93 publications

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“…Decreases in the amplitudes of ABR peak I in aging human subjects are consistent with a cochlear neuropathy and could underlie these temporal processing defects (Konrad-Martin, Dille et al 2012). Similar declines (>50%) across lifespan in ABR peak I amplitudes have also been demonstrated in mice (Sergeyenko, Lall et al 2013, Muniak, Ayeni et al 2018). While these mice exhibit a gradual increase in auditory thresholds over the course of their life span, this appears to be driven largely by OHC loss at later ages.…”

Section: Causes Of Hhlsupporting

confidence: 77%

Hidden Hearing Loss: A Disorder with Multiple Etiologies and Mechanisms

Kohrman

Wan

Cassinotti

et al. 2019

Cold Spring Harb Perspect Med

102

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Hidden hearing loss (HHL), a recently described auditory disorder, has been proposed to affect auditory neural processing and hearing acuity in subjects with normal audiometric thresholds, particularly in noisy environments. In contrast to central auditory processing disorders, HHL is caused by defects in the cochlea, the peripheral auditory organ. Noise exposure, aging, ototoxic drugs and peripheral neuropathies are some of the known risk factors for HHL. Our knowledge of the causes and mechanisms of HHL are based primarily on animal models. However, recent clinical studies have also shed light on the etiology and prevalence of this cochlear disorder and how it may affect auditory perception in humans. Here, we review the current knowledge regarding the causes and cellular mechanisms of HHL, summarize information on available noninvasive tests for differential diagnosis, and discuss potential therapeutic approaches for treatment of HHL.

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Section: Causes Of Hhlsupporting

confidence: 77%

Hidden Hearing Loss: A Disorder with Multiple Etiologies and Mechanisms

Kohrman

Wan

Cassinotti

et al. 2019

Cold Spring Harb Perspect Med

102

View full text Add to dashboard Cite

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“…Therefore, ABR is frequently used to assess hearing levels, as it exhibits good objectivity and stability (56). In CBA mice, the amplitudes of ABR I and II waves decrease with age (although the I wave is more pronounced), and the threshold increases with age (57); similar findings have been reported in the aging Fisher Brown Norway rat model, where the amplitude of ABR I waves decreases, and the threshold increases with age (46). A review of early studies reported that the latency delays of ABR I and III waves are marked when AHL occurs (58).…”

Section: Discussionsupporting

confidence: 80%

Age‑associated variation in the expression and function of TMEM16A calcium‑activated chloride channels in the cochlear stria vascularis of guinea pigs

et al. 2019

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The present study was designed to investigate the expression and function of transmembrane protein 16 (TMEM16A), a calcium-activated chloride channel (CaCC), in the stria vascularis (SV) of the cochlea of guinea pigs at different ages, and to understand the role of CaCCs in the pathogenesis of presbycusis (age-related hearing loss), the most common type of sensorineural hearing loss that occurs with natural aging. Guinea pigs were divided into the following groups: 2 weeks (young group), 3 months (youth group), 1 year (adult group), D-galactose intervention (D-gal group; aging model induced by subcutaneous injection of D-galactose) and T16Ainh-A01 (intraperitoneal injection of 50 µg/kg/day TMEM16A inhibitor T16Ainh-A01 for 2 weeks). Differences in the hearing of guinea pigs between the various age groups were analyzed using auditory brainstem response (ABR), and immunofluorescence staining was performed to detect TMEM16A expression in the SV and determine the distribution. Reverse transcription-quantitative PCR and western blot analyses were conducted to detect the mRNA and protein levels of TMEM16A in SV in the different age groups. Morris water maze behavior analysis demonstrated that spatial learning ability and memory were damaged in the D-gal group. Superoxide dismutase activity and malondialdehyde content assays indicated that there was oxidative stress damage in the D-gal group. The ABR thresholds gradually increased with age, and the increase in the T16Ainh-A01 group was pronounced. Immunofluorescence analysis in the cochlear SV of guinea pigs in different groups revealed that expression of TMEM16A increased with increasing age (2 weeks to 1 year); fluorescence intensity was reduced in the D-gal model of aging. As the guinea pigs continued to mature, the protein and mRNA contents of TMEM16A in the cochlea SV increased gradually, but were decreased in the D-gal group. The findings indicated that CaCCs in the cochlear SV of guinea pigs were associated with the development of hearing in guinea pigs, and that downregulation of TMEM16A may be associated with age-associated hearing loss.

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“…However, the latencies – the time of the response after the stimulus - of the PACAP-deficient mice showed a bit faster neuronal activation and transmission. Decreased amplitude and latency values are probably the subtle indications of hearing impairment not revealed by hearing threshold measurements 52,53 . During the analysis of individual waves, the labelling of the peaks of PACAP-deficient mice was often cumbersome because of peak fusions.…”

Section: Discussionmentioning

confidence: 98%

Hearing impairment and associated morphological changes in pituitary adenylate cyclase activating polypeptide (PACAP)-deficient mice

Fulop

Humli

Szepesy

et al. 2019

Sci Rep

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Pituitary adenylate cyclase activating polypeptide (PACAP) is a regulatory and cytoprotective neuropeptide, its deficiency implies accelerated aging in mice. It is present in the auditory system having antiapoptotic effects. Expression of Ca2+-binding proteins and its PAC1 receptor differs in the inner ear of PACAP-deficient (KO) and wild-type (WT) mice. Our aim was to elucidate the functional role of PACAP in the auditory system. Auditory brainstem response (ABR) tests found higher hearing thresholds in KO mice at click and low frequency burst stimuli. Hearing impairment at higher frequencies showed as reduced ABR wave amplitudes and latencies in KO animals. Increase in neuronal activity, demonstrated by c-Fos immunolabeling, was lower in KO mice after noise exposure in the ventral and dorsal cochlear nuclei. Noise induced neuronal activation was similar in further relay nuclei of the auditory pathway of WT and KO mice. Based on the similar inflammatory and angiogenic protein profile data from cochlear duct lysates, neither inflammation nor disturbed angiogenesis, as potential pathological components in sensorineural hearing losses, seem to be involved in the pathomechanism of the presented functional and morphological changes in PACAP KO mice. The hearing impairment is probably concomitant with the markedly accelerated aging processes in these animals.

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Hidden hearing loss and endbulbs of Held: Evidence for central pathology before detection of ABR threshold increases

Cited by 36 publications

References 93 publications

Hidden Hearing Loss: A Disorder with Multiple Etiologies and Mechanisms

Hidden Hearing Loss: A Disorder with Multiple Etiologies and Mechanisms

Age‑associated variation in the expression and function of TMEM16A calcium‑activated chloride channels in the cochlear stria vascularis of guinea pigs

Hearing impairment and associated morphological changes in pituitary adenylate cyclase activating polypeptide (PACAP)-deficient mice

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