Linking anatomical and physiological markers of auditory system degeneration with behavioral hearing assessments in a mouse (Mus musculus) model of age-related hearing loss

Kobrina, Anastasiya; Schrode, Katrina M.; Screven, Laurel A.; Javaid, Hamad; Weinberg, Madison M.; Brown, Garrett Wallace; Board, Ryleigh; Villavisanis, Dillan F.; Dent, Micheal L.; Lauer, Amanda M.

doi:10.1016/j.neurobiolaging.2020.08.012

Cited by 39 publications

(49 citation statements)

References 75 publications

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“…Although progress has been made in defining some of the genetic and cellular functions that are disrupted by ARHL, little is known about its underlying causes. Sensory ARHL involves loss or degeneration of sensory hair cells and their neural connections in the cochlea ( Lauer et al, 2012 ; Altschuler et al, 2015 ; Jeng et al, 2020a , b ; Kobrina et al, 2020 ). Inner hair cells (IHCs) contact the majority of neural connections and transmit sound-induced impulses to the brain.…”

Section: Introductionmentioning

confidence: 99%

“…The loss of OHCs leads to elevated hearing thresholds and loss of cochlear frequency tuning. Comparisons of behavioral and physiological hearing depreciation in mice indicate that behavioral repercussions of ARHL occur earlier than the more dramatic physical changes of cochlear damage ( Kobrina et al, 2020 ). Therefore, the molecular details of OHC dysfunction and synaptic loss are essential missing pieces in understanding the progression of ARHL in humans and mice.…”

Section: Introductionmentioning

confidence: 99%

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Deletion of Oncomodulin Gives Rise to Early Progressive Cochlear Dysfunction in C57 and CBA Mice

Climer

Hornak

Murtha

et al. 2021

Front. Aging Neurosci.

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Ca2+ signaling is a major contributor to sensory hair cell function in the cochlea. Oncomodulin (OCM) is a Ca2+ binding protein (CaBP) preferentially expressed in outer hair cells (OHCs) of the cochlea and few other specialized cell types. Here, we expand on our previous reports and show that OCM delays hearing loss in mice of two different genetic backgrounds: CBA/CaJ and C57Bl/6J. In both backgrounds, genetic disruption of Ocm leads to early progressive hearing loss as measured by auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE). In both strains, loss of Ocm reduced hearing across lifetime (hearing span) by more than 50% relative to wild type (WT). Even though the two WT strains have very different hearing spans, OCM plays a considerable and similar role within their genetic environment to regulate hearing function. The accelerated age-related hearing loss (ARHL) of the Ocm KO illustrates the importance of Ca2+ signaling in maintaining hearing health. Manipulation of OCM and Ca2+ signaling may reveal important clues to the systems of function/dysfunction that lead to ARHL.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Deletion of Oncomodulin Gives Rise to Early Progressive Cochlear Dysfunction in C57 and CBA Mice

Climer

Hornak

Murtha

et al. 2021

Front. Aging Neurosci.

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show abstract

“…Increased cochlear pigmentation has been observed in African-American individuals (Sun et al, 2014), which correlates with lower risk of noise-induced hearing loss and presbycusis observed in population based studies (Ishii and Talbott, 1998;Lin et al, 2012). Interestingly, in a mouse model of age-related hearing loss, pigment within the SV was observed to increase with age (Kobrina et al, 2020). Similar qualitative observations have been reported in other species (Takahashi, 1971;Keithley et al, 1992;Ohlemiller et al, 2006), raising the question of whether differences in cochlear pigmentation are simply differential responses to the aging process or whether pigmentation has a protective effect.…”

Section: Introductionmentioning

confidence: 81%

“…Mice were housed individually or in groups with unrestricted access to food and water and kept on a 12:12 h day/night cycle. Some of these animals underwent auditory response brainstem (ABR) testing that has been described elsewhere (Kobrina et al, 2020). Temporal bones were harvested from mice at 3-4 weeks and 20-32 months of age.…”

Section: Mouse Temporal Bone Subjects and Imagingmentioning

confidence: 99%

Comparison of Age-Related Pigmentary Changes in the Auditory and Vestibular Systems Within Mouse and Human Temporal Bones

et al. 2021

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BackgroundMelanin pigmentation is present within the auditory and vestibular systems of the mammalian inner ear and may play a role in maintaining auditory and vestibular function. Melanocytes within the stria vascularis (SV) are necessary for the generation of the endocochlear potential (EP) and decreased EP has been linked to age-related hearing loss. Melanocytes and pigment-containing “dark cells” are present within the vestibular system, but have a less well-defined role. African–American individuals have increased pigmentation within the SV and vestibular system, which is hypothesized to be related to lower rates of age-related hearing loss and vestibular dysfunction. It remains unclear if increased pigmentation confers lifelong protection against hearing loss and vestibular dysfunction.MethodsMouse temporal bones were collected from juvenile (3–4 week) and aged (20–32 months) CBA/CaJ mice. Pediatric and adult human temporal bones from Caucasian or African–American individuals were examined from the Johns Hopkins Temporal Bone Collection. Information regarding Fitzpatrick skin type were unavailable, and self-identified race/ethnicity was used as a proxy. Images were taken using light microscopy at 20× magnification. ImageJ software (v1.53) was used to measure pigment within the SV and vestibular system.ResultsIn mouse temporal bones pigmentation within the SV increased with age, but pigmentation within the vestibular system did not increase with age. In human temporal bones pigmentation within the SV increased with age and pigmentation within the vestibular system increased within the wall of the utricle, but not other regions of the vestibular system. African–American individuals had higher amounts of pigment within the SV and vestibular system, among both pediatric and adult populations.ConclusionStria vascularis pigmentation increases with age in mouse and human temporal bones. Pigmentation within the vestibular system did not increase with age in mouse specimens and only increased within the utricular wall with age in human specimens. Individuals who identified as African–American had higher pigment content within the SV and vestibular system, both as children and as adults. These results highlight how similar age-related pigmentary changes occur in the auditory and vestibular systems across species and underscore the importance of racial/ethnic diversity in human temporal bone studies.

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“…Although progress has been made in defining some of the genetic and cellular functions that are disrupted by ARHL, little is known about its underlying causes. Sensory ARHL involves loss or degeneration of sensory hair cells and their neural connections in the cochlea (Lauer et al, 2012;Altschuler et al, 2015;Jeng et al, 2020a,b;Kobrina et al, 2020). Inner hair cells (IHCs) contact the majority of neural connections and transmit sound-induced impulses to the brain.…”

Section: Introductionmentioning

confidence: 99%

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Linking anatomical and physiological markers of auditory system degeneration with behavioral hearing assessments in a mouse (Mus musculus) model of age-related hearing loss

Cited by 39 publications

References 75 publications

Deletion of Oncomodulin Gives Rise to Early Progressive Cochlear Dysfunction in C57 and CBA Mice

Deletion of Oncomodulin Gives Rise to Early Progressive Cochlear Dysfunction in C57 and CBA Mice

Comparison of Age-Related Pigmentary Changes in the Auditory and Vestibular Systems Within Mouse and Human Temporal Bones

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