ADAM10 and γ-Secretase Regulate Sensory Regeneration in the Avian Vestibular Organs.

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ADAM10 and γ-Secretase Regulate Sensory Regeneration in the Avian Vestibular Organs.

Dev Biol. 2017 May 16;:

Authors: Warchol ME, Stone J, Barton M, Ku J, Veile R, Daudet N, Lovett M

Abstract
The loss of sensory hair cells from the inner ear is a leading cause of hearing and balance disorders. The mammalian ear has a very limited ability to replace lost hair cells, but the inner ears of non-mammalian vertebrates can spontaneously regenerate hair cells after injury. Prior studies have shown that replacement hair cells are derived from epithelial supporting cells and that the differentiation of new hair cells is regulated by the Notch signaling pathway. The present study examined molecular influences on regeneration in the avian utricle, which has a particularly robust regenerative ability. Chicken utricles were placed in organotypic culture and hair cells were lesioned by application of the ototoxic antibiotic streptomycin. Cultures were then allowed to regenerate in vitro for seven days. Some specimens were treated with small molecule inhibitors of γ-secretase or ADAM10, proteases which are essential for transmission of Notch signaling. As expected, treatment with both inhibitors led to increased numbers of replacement hair cells. However, we also found that inhibition of both proteases resulted in increased regenerative proliferation. Subsequent experiments showed that inhibition of γ-secretase or ADAM10 could also trigger proliferation in undamaged utricles. To better understand these phenomena, we used RNA-Seq profiling to characterize changes in gene expression following γ-secretase inhibition. We observed expression patterns that were consistent with Notch pathway inhibition, but we also found that the utricular sensory epithelium contains numerous γ-secretase substrates that might regulate cell cycle entry and possibly supporting cell-to-hair cell conversion. Together, our data suggest multiple roles for γ-secretase and ADAM10 in vestibular hair cell regeneration.

PMID: 28526588 [PubMed - as supplied by publisher]

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ADAM10 and γ-Secretase Regulate Sensory Regeneration in the Avian Vestibular Organs.

Related Articles

ADAM10 and γ-Secretase Regulate Sensory Regeneration in the Avian Vestibular Organs.

Dev Biol. 2017 May 16;:

Authors: Warchol ME, Stone J, Barton M, Ku J, Veile R, Daudet N, Lovett M

Abstract
The loss of sensory hair cells from the inner ear is a leading cause of hearing and balance disorders. The mammalian ear has a very limited ability to replace lost hair cells, but the inner ears of non-mammalian vertebrates can spontaneously regenerate hair cells after injury. Prior studies have shown that replacement hair cells are derived from epithelial supporting cells and that the differentiation of new hair cells is regulated by the Notch signaling pathway. The present study examined molecular influences on regeneration in the avian utricle, which has a particularly robust regenerative ability. Chicken utricles were placed in organotypic culture and hair cells were lesioned by application of the ototoxic antibiotic streptomycin. Cultures were then allowed to regenerate in vitro for seven days. Some specimens were treated with small molecule inhibitors of γ-secretase or ADAM10, proteases which are essential for transmission of Notch signaling. As expected, treatment with both inhibitors led to increased numbers of replacement hair cells. However, we also found that inhibition of both proteases resulted in increased regenerative proliferation. Subsequent experiments showed that inhibition of γ-secretase or ADAM10 could also trigger proliferation in undamaged utricles. To better understand these phenomena, we used RNA-Seq profiling to characterize changes in gene expression following γ-secretase inhibition. We observed expression patterns that were consistent with Notch pathway inhibition, but we also found that the utricular sensory epithelium contains numerous γ-secretase substrates that might regulate cell cycle entry and possibly supporting cell-to-hair cell conversion. Together, our data suggest multiple roles for γ-secretase and ADAM10 in vestibular hair cell regeneration.

PMID: 28526588 [PubMed - as supplied by publisher]

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Gender Differences in the Association between Moderate Alcohol Consumption and Hearing Threshold Shifts.

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Gender Differences in the Association between Moderate Alcohol Consumption and Hearing Threshold Shifts.

Sci Rep. 2017 May 19;7(1):2201

Authors: Lin YY, Chen HC, Lai WS, Wu LW, Wang CH, Lee JC, Kao TW, Chen WL

Abstract
Hearing loss is a global public health problem with a high prevalence, significantly impairing communication and leading to a decrease in the quality of life. The association between moderate alcohol consumption (MAC) and hearing impairment has been addressed in several studies with inconsistent results. The intent of our study is to clarify the correlation between MAC and the hearing threshold and further investigate the interplay between MAC and the hearing threshold categorized by gender. The study included 4,075 participants aged 20-69 years from the 1999-2004 data of National Health and Nutrition Examination Survey (NHANES). The associations among MAC, gender differences, and high-frequency and low-frequency hearing thresholds were analyzed. We found that current female drinkers with MAC tended to have lower hearing thresholds. There is a significant protective effect of MAC on hearing threshold shifts in the US adult population, especially in females. Our research was the first study to further indicate that there is a gender difference in the association between MAC and hearing impairment. In accordance with our results, if people drink, they should consume moderate rather than higher amounts, especially in women, which may result in a reduced risk of hearing loss.

PMID: 28526828 [PubMed - in process]

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