Reduced Connexin26 in the Mature Cochlea Increases Susceptibility to Noise-Induced Hearing Loss in Mice

Zhou, Xingxing; Chen, Sen; Xie, Le; Ji, Yu-Zi; Wu, Xia; Wang, Wenwen; Yang, Qi; Yu, Jintao; Sun, Yu; Lin, Xiaobo; Kong, Weijia

doi:10.3390/ijms17030301

Cited by 32 publications

(33 citation statements)

References 44 publications

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“…Recently, a study found that both Cx26 and Cx30 protein levels were significantly decreased after noise exposure (Yamaguchi et al, 2014). Since then, another study has shown that when Cx26 is conditionally knocked down at postnatal day 18, mice exhibit more pronounced noise-induced hearing loss than their wildtype (WT) counterparts (Zhou et al, 2016). At present, it is unknown whether patients harbouring GJA1 mutations are more susceptible to auditory damage after a loud noise exposure.…”

Section: Introductionmentioning

confidence: 99%

Mice harbouring an oculodentodigital dysplasia-linked Cx43 G60S mutation have severe hearing loss

Abitbol

Kelly

Barr

et al. 2018

Journal of Cell Science

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Given the importance of connexin43 (Cx43, encoded by ) function in the central nervous system and sensory organ processing, we proposed that it would also be crucial in auditory function. To that end, hearing was examined in two mouse models of oculodentodigital dysplasia that globally express mutations resulting in mild or severe loss of Cx43 function. Although Cx43 mutant mice, with ∼50% Cx43 channel function, did not have any hearing loss, Cx43 mutant mice, with ∼20% Cx43 channel function, had severe hearing loss. There was no evidence of inner ear sensory hair cell loss, suggesting that the mechanism for Cx43-linked hearing loss lies downstream in the auditory pathway. Since evidence suggests that Cx26 function is essential for hearing and may be protective against noise-induced hearing loss, we challenged Cx43 mice with a loud noise and found that they had a similar susceptibility to noise-induced hearing loss to that found in controls, suggesting that decreased Cx43 function does not sensitize the mice for environmentally induced hearing loss. Taken together, this study suggests that Cx43 plays an important role in baseline hearing and is essential for auditory processing.This article has an associated First Person interview with the first author of the paper.

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Section: Introductionmentioning

confidence: 99%

Mice harbouring an oculodentodigital dysplasia-linked Cx43 G60S mutation have severe hearing loss

Abitbol

Kelly

Barr

et al. 2018

Journal of Cell Science

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“…Humans with the V84L mutation in Cx26, which has intact junctional conductance but absent transmission of IP 3 , a Ca 2+ second messenger necessary for ICS activity, have hearing loss [18], suggesting that ICS activity is protective and its disruption central to the pathogenesis of Cx26-associated hearing loss. Finally, a recent study showed that Cx26 conditional knockout mice have increased susceptibility to noise-induced hearing loss, suggesting a common pathophysiologic mechanism underlying both forms of deafness [19]. …”

Section: Introductionmentioning

confidence: 99%

Sound-Induced Intracellular Ca2+ Dynamics in the Adult Hearing Cochlea

Chan

Rouse

2016

PLoS ONE

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Ca2+ signaling has been implicated in the initial pathophysiologic mechanisms underlying the cochlea's response to acoustic overstimulation. Intracellular Ca2+ signaling (ICS) waves, which occur in glia and retinal cells in response to injury to activate cell regulatory pathways, have been proposed as an early event in cochlear injury. Disruption of ICS activity is thought to underlie Connexin 26-associated hearing loss, the most common genetic form of deafness, and downstream sequelae of ICS wave activity, such as MAP kinase pathway activation, have been implicated in noise-induced hearing loss. However, ICS waves have only been observed in neonatal cochlear cultures and are thought to be quiescent after the onset of hearing. In this study, we employ an acute explant model of an adult, hearing cochlea that retains many in vivo physiologic features to investigate Ca2+ changes in response to sound. We find that both slow monotonic changes in intracellular Ca2+ concentration as well as discrete ICS waves occur with acoustic overstimulation. The ICS waves share many intrinsic features with their better-described neonatal counterparts, including ATP and gap-junction dependence, and propagation velocity and distance. This identification of ICS wave activity in the adult, hearing cochlea thus confirms and characterizes an important early detection mechanism for cochlear trauma and provides a target for interventions for noise-induced and Connexin 26-associated hearing loss.

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“…Burke et al and Kim et al a heterozygote ratio increases with normal hearing in a group with sensory hearing loss compared to the control group [26,27]. In rats, reduced expression of connexin 26 after 18 days of birth has increased the susceptibility of Corti's normal organ to acoustic trauma and degenerative lesions [28]. Van Eyken and his friends work.…”

Section: Resultsmentioning

confidence: 98%

Circulating cell free DNA and miRNA Amount in Congenital Hearing Loss

Çağlar¹,

Çayır²,

Cilgin³

et al. 2018

Acta Medica

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Objective: Our aim is to detect the amount of miRNA and free DNA in the peripheral blood of young people with congenital hearing loss and compare this with control group. Materials and Methods: In our study, 16 patients who have congenital hearing loss and go to the private school for deaf children and 16 healthy individuals were selected in the same age group. 5 cc blood was taken from peripheral vessels of each individual. We compared the circulating cell-free DNA and miRNA amount with the results of the control group. Results: The ccfDNA amount of the patients with hearing loss was lower than the control group and It was statistically significant. On the contrary, we found the higher amount of ccfmiRNA in plasma samples of the patients with hearing loss. The statistical analysis showed that ccfmiRNA amount in congenital loss is consistently significantly higher than the control group. Conclusion: The miRNA and freeDNA can be used early in the diagnosis of congenital hearing loss.

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Reduced Connexin26 in the Mature Cochlea Increases Susceptibility to Noise-Induced Hearing Loss in Mice

Cited by 32 publications

References 44 publications

Mice harbouring an oculodentodigital dysplasia-linked Cx43 G60S mutation have severe hearing loss

Mice harbouring an oculodentodigital dysplasia-linked Cx43 G60S mutation have severe hearing loss

Sound-Induced Intracellular Ca2+ Dynamics in the Adult Hearing Cochlea

Circulating cell free DNA and miRNA Amount in Congenital Hearing Loss

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