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The Role of Glucocorticoid-Related Signaling for Protection Against Noise-Induced Hearing Loss.

Record Type:	Electronic resources : Monograph/item
Title/Author:	The Role of Glucocorticoid-Related Signaling for Protection Against Noise-Induced Hearing Loss./
Author:	Barnes, Charles C.
Description:	1 online resource (269 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 84-10, Section: B.
Contained By:	Dissertations Abstracts International84-10B.
Subject:	Audiology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=30310497click for full text (PQDT)
ISBN:	9798379436797

The Role of Glucocorticoid-Related Signaling for Protection Against Noise-Induced Hearing Loss.
Barnes, Charles C.

The Role of Glucocorticoid-Related Signaling for Protection Against Noise-Induced Hearing Loss. - 1 online resource (269 pages)

Source: Dissertations Abstracts International, Volume: 84-10, Section: B.

Thesis (Ph.D.)--The University of Mississippi Medical Center, 2023.

Includes bibliographical references

Noise exposure is a primary risk factor for acquired hearing loss. Hearing loss diminishes perception of the environment and connection to society and can accelerate ageing in untreated people affected by hearing loss. The mammalian cochlea does not regenerate sensorineural components once lost to accumulate damage. Understanding endogenous protection strategies may reveal therapeutic targets. There are no FDA-approved drugs to treat noise-induced hearing loss, but synthetic glucocorticoids are used to preserve or recover residual hearing in people with immune-related hearing loss. Glucocorticoids do not always recover residual hearing. Various efficacy of glucocorticoids is related to the broad homeostatic roles of endogenous glucocorticoids. Glucocorticoid therapeutic mechanisms are unknown in relation to cell types contributing to cochlear-intrinsic homeostasis. Epithelial supporting cells in the cochlea are a heterogenous group which collectively maintain conditions necessary for reliable sensorineural function and are involved in damage mitigation. Understanding interactions of GC-related signaling with epithelial supporting cell functions during recovery from noise exposure may reveal targetable processes to improve therapeutic outcomes. The studies in this dissertation used mouse models for conditional genetic ablation of target receptors expressed in cochlear epithelial supporting cells. The first study targeted ablation of mineralocorticoid receptor or glucocorticoid receptor. Both are glucocorticoid-sensitive, ligand-activated nuclear receptors mediating transcriptional changes by endogenous glucocorticoids. Auditory physiology after mild noise exposure was recorded in the recovery period and associated with morphological measures of ribbon synapse counts and macrophage-like cell counts. Findings from the first study revealed that mineralocorticoid receptor ablation transiently exacerbated loss of physiological activity while glucocorticoid receptor ablation exacerbated physiological loss long-term after noise exposure. The outcomes are consistent with roles of each receptor in the literature. Glucocorticoid receptor is the major glucocorticoid-sensitive receptor expressed in supporting cells associating with outcome after noise exposure. The second study asked whether vulnerability to homeostatic challenge by noise exposure interacted with sound-induced adaptation against noise-induced damage. To assess this question, a sound preconditioning paradigm was used to induce protection against moderate noise exposure in two different mouse lines targeting either glucocorticoid receptor or corticotropin-releasing factor receptor 1 ablation in epithelial supporting cells. Auditory physiology outcome was recorded and ribbon synapses, outer hair cells, and macrophage-like cells were counted at the experiment end. Glucocorticoid receptor ablation impaired sound preconditioning protection against noise-induced physiological loss but ribbon synapses and outer hair cells could still be protected from noise-induced loss. Corticotropin releasing factor receptor 1 ablation improved sound preconditioning protection against noise-induced physiological loss, ribbon synapse loss, but not outer hair cell loss. Altogether, the studies in this dissertation demonstrate that receptors related to GC-signaling expressed in support cells differentially influence outcome after noise-induced homeostatic challenge and sound-preconditioned hormesis against noise-induced damage. The mechanisms contributing to these receptor-dependent influences by supporting cells will require further experimentation to reveal.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2023

Mode of access: World Wide Web

ISBN: 9798379436797Subjects--Topical Terms:

537237
Audiology.
Subjects--Index Terms:

CochleaIndex Terms--Genre/Form:

542853
Electronic books.

The Role of Glucocorticoid-Related Signaling for Protection Against Noise-Induced Hearing Loss.
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502 $a Thesis (Ph.D.)--The University of Mississippi Medical Center, 2023.
504 $a Includes bibliographical references
520 $a Noise exposure is a primary risk factor for acquired hearing loss. Hearing loss diminishes perception of the environment and connection to society and can accelerate ageing in untreated people affected by hearing loss. The mammalian cochlea does not regenerate sensorineural components once lost to accumulate damage. Understanding endogenous protection strategies may reveal therapeutic targets. There are no FDA-approved drugs to treat noise-induced hearing loss, but synthetic glucocorticoids are used to preserve or recover residual hearing in people with immune-related hearing loss. Glucocorticoids do not always recover residual hearing. Various efficacy of glucocorticoids is related to the broad homeostatic roles of endogenous glucocorticoids. Glucocorticoid therapeutic mechanisms are unknown in relation to cell types contributing to cochlear-intrinsic homeostasis. Epithelial supporting cells in the cochlea are a heterogenous group which collectively maintain conditions necessary for reliable sensorineural function and are involved in damage mitigation. Understanding interactions of GC-related signaling with epithelial supporting cell functions during recovery from noise exposure may reveal targetable processes to improve therapeutic outcomes. The studies in this dissertation used mouse models for conditional genetic ablation of target receptors expressed in cochlear epithelial supporting cells. The first study targeted ablation of mineralocorticoid receptor or glucocorticoid receptor. Both are glucocorticoid-sensitive, ligand-activated nuclear receptors mediating transcriptional changes by endogenous glucocorticoids. Auditory physiology after mild noise exposure was recorded in the recovery period and associated with morphological measures of ribbon synapse counts and macrophage-like cell counts. Findings from the first study revealed that mineralocorticoid receptor ablation transiently exacerbated loss of physiological activity while glucocorticoid receptor ablation exacerbated physiological loss long-term after noise exposure. The outcomes are consistent with roles of each receptor in the literature. Glucocorticoid receptor is the major glucocorticoid-sensitive receptor expressed in supporting cells associating with outcome after noise exposure. The second study asked whether vulnerability to homeostatic challenge by noise exposure interacted with sound-induced adaptation against noise-induced damage. To assess this question, a sound preconditioning paradigm was used to induce protection against moderate noise exposure in two different mouse lines targeting either glucocorticoid receptor or corticotropin-releasing factor receptor 1 ablation in epithelial supporting cells. Auditory physiology outcome was recorded and ribbon synapses, outer hair cells, and macrophage-like cells were counted at the experiment end. Glucocorticoid receptor ablation impaired sound preconditioning protection against noise-induced physiological loss but ribbon synapses and outer hair cells could still be protected from noise-induced loss. Corticotropin releasing factor receptor 1 ablation improved sound preconditioning protection against noise-induced physiological loss, ribbon synapse loss, but not outer hair cell loss. Altogether, the studies in this dissertation demonstrate that receptors related to GC-signaling expressed in support cells differentially influence outcome after noise-induced homeostatic challenge and sound-preconditioned hormesis against noise-induced damage. The mechanisms contributing to these receptor-dependent influences by supporting cells will require further experimentation to reveal.
533 $a Electronic reproduction. $b Ann Arbor, Mich. : $c ProQuest, $d 2023
538 $a Mode of access: World Wide Web
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650 4 $a Pathology. $3 643180
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