Glucose Protects Cochlear Hair Cells Against Oxidative Stress and Attenuates Noise-Induced Hearing Loss in Mice

2021 ◽  
Author(s):  
Hao Xiong ◽  
Lan Lai ◽  
Yongyi Ye ◽  
Yiqing Zheng
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
Hair Cells ◽  
Noise Induced Hearing Loss ◽  
Cochlear Hair Cells

scholarly journals Outcomes of Peptide Vaccine GV1001 Treatment in a Murine Model of Acute Noise-Induced Hearing Loss

Antioxidants ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 112
Author(s):  
Sang-Yeon Lee ◽  
Jae Joon Han ◽  
Sang-Youp Lee ◽  
Gaon Jung ◽  
Hyun Jin Min ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
White Noise ◽  
Hair Cells ◽  
Murine Model ◽  
Outer Hair Cells ◽  
Saline Control ◽  
Noise Induced Hearing Loss ◽  
Cochlear Hair Cells ◽  
Ribbon Synapses

Noise-induced hearing loss (NIHL) is primarily caused by damage to cochlear hair cells, associated with synaptopathy. The novel cell-penetrating peptide GV1001, an antitumor agent, also has antioxidant and anti-inflammatory effects, and is otoprotective in a murine model of kanamycin-induced ototoxicity. Here, we explored whether GV1001 attenuated NIHL, and the underlying mechanism at play. We established an NIHL model by exposing 4- to 6-week-old C57/BL6 mice to white noise at 120 dB SPL for 2 h, resulting in a significant permanent threshold shift (PTS). We then subcutaneously injected saline (control), GV1001, or dexamethasone immediately after cessation of PTS-noise exposure and evaluated the threshold shifts, structural damages to outer hair cells (OHCs), and ribbon synapses. We also verified whether GV1001 attenuates oxidative stress at the level of lipid peroxidation or protein nitration in OHCs 1 h after exposure to white noise at 120 dB SPL. GV1001-treated mice exhibited significantly less hearing threshold shifts over 2 weeks and preserved OHCs and ribbon synapses compared with controls. Similarly, dexamethasone-treated mice showed comparable protection against NIHL. Importantly, GV1001 markedly attenuated oxidative stress in OHCs. Our findings suggest that GV1001 may protect against NIHL by lowering oxidative stress and may serve as preventive or adjuvant treatment.

Regeneration of Cochlear Hair Cells with Atoh1 Gene Therapy after Noise-Induced Hearing Loss

2015 ◽  
Vol 04 (01) ◽  
Author(s):  
Andrew K Wise Brianna O Flynn ◽  
Patrick J Atkinson ◽  
James B Fallon ◽  
Madeline Nicholson
Keyword(s):  
Gene Therapy ◽  
Hearing Loss ◽  
Hair Cells ◽  
Noise Induced Hearing Loss ◽  
Cochlear Hair Cells

Fluorocitrate Neural Dystrophy of the Guinea Pig Cochlea

1975 ◽  
Vol 33 ◽  
pp. 368-369
Author(s):  
G.J. Spector ◽  
C.D. Carr ◽  
I. Kaufman Arenberg ◽  
R.H. Maisel
Keyword(s):  
Hearing Loss ◽  
Hair Cells ◽  
Sodium Phosphate ◽  
Sensory Cells ◽  
Barium Salt ◽  
Perfusion Medium ◽  
Cochlear Hair Cells ◽  
Neural Degeneration ◽  
Sodium Phosphate Buffer ◽  
Cochlear Neurons

All studies on primary neural degeneration in the cochlea have evaluated the end stages of degeneration or the indiscriminate destruction of both sensory cells and cochlear neurons. We have developed a model which selectively simulates the dystrophic changes denoting cochlear neural degeneration while sparing the cochlear hair cells. Such a model can be used to define more precisely the mechanism of presbycusis or the hearing loss in aging man.Twenty-two pigmented guinea pigs (200-250 gm) were perfused by the perilymphatic route as live preparations using fluorocitrate in various concentrations (15-250 ug/cc) and at different incubation times (5-150 minutes). The barium salt of DL fluorocitrate, (C6H4O7F)2Ba3, was reacted with 1.0N sulfuric acid to precipitate the barium as a sulfate. The perfusion medium was prepared, just prior to use, as follows: sodium phosphate buffer 0.2M, pH 7.4 = 9cc; fluorocitrate = 15-200 mg/cc; and sucrose = 0.2M.

MicroRNAs in Noise-Induced Hearing Loss and their Regulation by Oxidative Stress and Inflammation

2020 ◽  
Vol 21 (12) ◽  
pp. 1216-1224
Author(s):  
Fatemeh Forouzanfar ◽  
Samira Asgharzade
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
Hair Cell ◽  
Noise Exposure ◽  
Cell Damage ◽  
Sensory Cells ◽  
Noise Induced Hearing Loss ◽  
Irreversible Damage ◽  
Open Access Journals

Noise exposure (NE) has been recognized as one of the causes of sensorineural hearing loss (SNHL), which can bring about irreversible damage to sensory hair cells in the cochlea, through the launch of oxidative stress pathways and inflammation. Accordingly, determining the molecular mechanism involved in regulating hair cell apoptosis via NE is essential to prevent hair cell damage. However, the role of microRNAs (miRNAs) in the degeneration of sensory cells of the cochlea during NE has not been so far uncovered. Thus, the main purpose of this study was to demonstrate the regulatory role of miRNAs in the oxidative stress pathway and inflammation induced by NE. In this respect, articles related to noise-induced hearing loss (NIHL), oxidative stress, inflammation, and miRNA from various databases of Directory of Open Access Journals (DOAJ), Google Scholar, PubMed; Library, Information Science & Technology Abstracts (LISTA), and Web of Science were searched and retrieved. The findings revealed that several studies had suggested that up-regulation of miR-1229-5p, miR-451a, 185-5p, 186 and down-regulation of miRNA-96/182/183 and miR-30b were involved in oxidative stress and inflammation which could be used as biomarkers for NIHL. There was also a close relationship between NIHL and miRNAs, but further research is required to prove a causal association between miRNA alterations and NE, and also to determine miRNAs as biomarkers indicating responses to NE.

scholarly journals Primed to die: an investigation of the genetic mechanisms underlying noise-induced hearing loss and cochlear damage in homozygous Foxo3-knockout mice

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Holly J. Beaulac ◽  
Felicia Gilels ◽  
Jingyuan Zhang ◽  
Sarah Jeoung ◽  
Patricia M. White
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
Noise Exposure ◽  
Multiphoton Microscopy ◽  
Cell Loss ◽  
Outer Hair Cells ◽  
Noise Induced Hearing Loss ◽  
Knock Out ◽  
Cell Death Pathway ◽  
Cochlear Damage

AbstractThe prevalence of noise-induced hearing loss (NIHL) continues to increase, with limited therapies available for individuals with cochlear damage. We have previously established that the transcription factor FOXO3 is necessary to preserve outer hair cells (OHCs) and hearing thresholds up to two weeks following mild noise exposure in mice. The mechanisms by which FOXO3 preserves cochlear cells and function are unknown. In this study, we analyzed the immediate effects of mild noise exposure on wild-type, Foxo3 heterozygous (Foxo3+/−), and Foxo3 knock-out (Foxo3−/−) mice to better understand FOXO3’s role(s) in the mammalian cochlea. We used confocal and multiphoton microscopy to examine well-characterized components of noise-induced damage including calcium regulators, oxidative stress, necrosis, and caspase-dependent and caspase-independent apoptosis. Lower immunoreactivity of the calcium buffer Oncomodulin in Foxo3−/− OHCs correlated with cell loss beginning 4 h post-noise exposure. Using immunohistochemistry, we identified parthanatos as the cell death pathway for OHCs. Oxidative stress response pathways were not significantly altered in FOXO3’s absence. We used RNA sequencing to identify and RT-qPCR to confirm differentially expressed genes. We further investigated a gene downregulated in the unexposed Foxo3−/− mice that may contribute to OHC noise susceptibility. Glycerophosphodiester phosphodiesterase domain containing 3 (GDPD3), a possible endogenous source of lysophosphatidic acid (LPA), has not previously been described in the cochlea. As LPA reduces OHC loss after severe noise exposure, we treated noise-exposed Foxo3−/− mice with exogenous LPA. LPA treatment delayed immediate damage to OHCs but was insufficient to ultimately prevent their death or prevent hearing loss. These results suggest that FOXO3 acts prior to acoustic insult to maintain cochlear resilience, possibly through sustaining endogenous LPA levels.

Outer hair cells in the mammalian cochlea and noise-induced hearing loss

Nature ◽  
1985 ◽  
Vol 315 (6021) ◽  
pp. 662-665 ◽  
Author(s):  
A. R. Cody ◽  
I. J. Russell
Keyword(s):  
Hearing Loss ◽  
Hair Cells ◽  
Outer Hair Cells ◽  
Noise Induced Hearing Loss

scholarly journals Effects of cochlear hair cell ablation on spatial learning/memory

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Z. Jason Qian ◽  
Anthony J. Ricci
Keyword(s):  
Hearing Loss ◽  
Hair Cell ◽  
Spatial Learning ◽  
Hair Cells ◽  
Noise Exposure ◽  
Memory Errors ◽  
Cochlear Hair Cells ◽  
Cochlear Hair Cell ◽  
Cell Ablation ◽  
Spatial Learning Memory

AbstractCurrent clinical interest lies in the relationship between hearing loss and cognitive impairment. Previous work demonstrated that noise exposure, a common cause of sensorineural hearing loss (SNHL), leads to cognitive impairments in mice. However, in noise-induced models, it is difficult to distinguish the effects of noise trauma from subsequent SNHL on central processes. Here, we use cochlear hair cell ablation to isolate the effects of SNHL. Cochlear hair cells were conditionally and selectively ablated in mature, transgenic mice where the human diphtheria toxin (DT) receptor was expressed behind the hair-cell specific Pou4f3 promoter. Due to higher Pou4f3 expression in cochlear hair cells than vestibular hair cells, administration of a low dose of DT caused profound SNHL without vestibular dysfunction and had no effect on wild-type (WT) littermates. Spatial learning/memory was assayed using an automated radial 8-arm maze (RAM), where mice were trained to find food rewards over a 14-day period. The number of working memory errors (WME) and reference memory errors (RME) per training day were recorded. All animals were injected with DT during P30–60 and underwent the RAM assay during P90–120. SNHL animals committed more WME and RME than WT animals, demonstrating that isolated SNHL affected cognitive function. Duration of SNHL (60 versus 90 days post DT injection) had no effect on RAM performance. However, younger age of acquired SNHL (DT on P30 versus P60) was associated with fewer WME. This describes the previously undocumented effect of isolated SNHL on cognitive processes that do not directly rely on auditory sensory input.

scholarly journals Multiphoton NAD(P)H FLIM reveals metabolic changes in individual cell types of the intact cochlea upon sensorineural hearing loss

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Paromita Majumder ◽  
Thomas S. Blacker ◽  
Lisa S. Nolan ◽  
Michael R. Duchen ◽  
Jonathan E. Gale
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
Cell Model ◽  
Organ Of Corti ◽  
Cell Types ◽  
Fluorescence Lifetime Imaging ◽  
Noise Induced Hearing Loss ◽  
Label Free ◽  
Age Related ◽  
The Individual

AbstractAn increasing volume of data suggests that changes in cellular metabolism have a major impact on the health of tissues and organs, including in the auditory system where metabolic alterations are implicated in both age-related and noise-induced hearing loss. However, the difficulty of access and the complex cyto-architecture of the organ of Corti has made interrogating the individual metabolic states of the diverse cell types present a major challenge. Multiphoton fluorescence lifetime imaging microscopy (FLIM) allows label-free measurements of the biochemical status of the intrinsically fluorescent metabolic cofactors NADH and NADPH with subcellular spatial resolution. However, the interpretation of NAD(P)H FLIM measurements in terms of the metabolic state of the sample are not completely understood. We have used this technique to explore changes in metabolism associated with hearing onset and with acquired (age-related and noise-induced) hearing loss. We show that these conditions are associated with altered NAD(P)H fluorescence lifetimes, use a simple cell model to confirm an inverse relationship between τbound and oxidative stress, and propose such changes as a potential index of oxidative stress applicable to all mammalian cell types.

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