Research

CATEGORY:
Research

SCREENSHOT:

TITLE:
Congenital Deafness and Recent Advances Towards Restoring Hearing Loss

CONTENT:
Curr Protoc. 2021 Mar;1(3):e76. doi: 10.1002/cpz1.76.

ABSTRACT

Congenital hearing loss is the most common birth defect, estimated to affect 2-3 in every 1000 births. Currently there is no cure for hearing loss. Treatment options are limited to hearing aids for mild and moderate cases, and cochlear implants for severe and profound hearing loss. Here we provide a literature overview of the environmental and genetic causes of congenital hearing loss, common animal models and methods used for hearing research, as well as recent advances towards developing therapies to treat congenital deafness. © 2021 The Authors.

PMID:33780161 | DOI:10.1002/cpz1.76

SOURCE:
Current protocols

PUBLISHER:

PMID:
pubmed:33780161

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33780161

DOI:
10.1002/cpz1.76

DATE – PUBLISHED:
Mon, 29 Mar 2021 06:00:00 -0400

DATE – DOI:
2021-03-29T13:07:03Z

DATE – ADDED:
03/30/21 12:08AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33780161/

LINK – DOI:
https://doi.org/10.1002/cpz1.76

LINK – PUBLISHER:
https://onlinelibrary.wiley.com/doi/10.1002/cpz1.76?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-03-30T04:08:44+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

SCREENSHOT:

TITLE:
Expression of serum proteins in noise induced hearing loss workers of mining based industry

CONTENT:
J Proteomics. 2021 Mar 15:104185. doi: 10.1016/j.jprot.2021.104185. Online ahead of print.

ABSTRACT

Noise Induced Hearing Loss (NIHL) is caused by excessive noise exposure due to occupational activities thus affects communication and quality of life. Prolonged occupational and environmental exposure to loud noise damages key molecules present in the micro-machinery of the ear which are required for the mechano-electrical transduction of sound waves in cochlea. Specific proteins are known to be associated with hearing loss and related structural and functional disabilities in the human inner, outer hair cells and cochlea. Rationale of this study was to identify the cochlear proteins associated with the pathophysiology of NIHL using proteomic approaches in mining based industrial workers. Total (n = 210) samples were collected from mining based industrial workers of central India. Subjects were categorized based on audiometric analysis. Proteome changes of the host serum were investigated using one and two-dimensional electrophoresis in combination with LC-MS/MS and MALDI-TOF MS. Up-regulated 46 cochlear proteins among confirmed NIHL cases were identified by MASCOT. Shrinkage discriminant analysis provided top 25 discriminating feature proteins namely myosin, transthyretin, SERPIN, CCDC50, enkurin, transferin etc. The identified potential proteins may be used as biomarkers for early detection and to understand the pathogenic mechanism of NIHL. Evaluation of these biomarkers in follow-up cases may further aid in improving NIHL diagnosis. SIGNIFICANCE: Human proteome study in Noise Induced Hearing Loss (NIHL) cases has not been published till date. This study represents most comprehensive proteomic analysis in NIHL cases taken from Indian mine workers. The identified key twenty-five discriminating feature proteins which are upregulated when an individual develops (or is in stage of development of) NIHL, provides insights into the potential roles of these varied proteins in disease progression. The proteins thus identified by proteomic approach may be used as early diagnostic biomarker to predict the occurrence of disease at very early stage.

PMID:33737237 | DOI:10.1016/j.jprot.2021.104185

SOURCE:
Journal of proteomics

PUBLISHER:

PMID:
pubmed:33737237

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33737237

DOI:
10.1016/j.jprot.2021.104185

DATE – PUBLISHED:
Fri, 19 Mar 2021 06:00:00 -0400

DATE – DOI:
2021-03-18T20:32:33Z

DATE – ADDED:
03/19/21 03:00PM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33737237/

LINK – DOI:
https://doi.org/10.1016/j.jprot.2021.104185

LINK – PUBLISHER:
https://linkinghub.elsevier.com/retrieve/pii/S1874391921000841?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-03-19T19:00:02+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

SCREENSHOT:

TITLE:
T2 relaxation time shortening in the cochlea of patients with sudden sensory neuronal hearing loss: a retrospective study using quantitative synthetic magnetic resonance imaging

CONTENT:
Eur Radiol. 2021 Feb 20. doi: 10.1007/s00330-021-07749-5. Online ahead of print.

ABSTRACT

OBJECTIVES: High cochlear signal intensity on three-dimensional (3D) T2 fluid-attenuated inversion recovery (FLAIR) sequences in patients with sudden sensorineural hearing loss (SSNHL) has been reported. Here, we evaluated the cochlear T2 relaxation time differences in patients with idiopathic SSNHL using quantitative synthetic MRI (SyMRI).

METHODS: Twenty-four patients with unilateral SSNHL who underwent precontrast conventional 3D FLAIR and SyMRI were retrospectively included. T1 and T2 relaxation times and the proton density (PD) of the bilateral ears were measured by manually drawn regions of interest. Wilcoxon signed-rank tests and intra- and interobserver correlation analyses were performed. Qualitative analysis was also performed to determine the presence and laterality of the asymmetric high signal intensity on synthetic FLAIR (SyFLAIR) images.

RESULTS: The T2 relaxation time was significantly lower in the affected (basal and apico-middle turns) than in the unaffected cochlea (basal turn: 519 ± 181.3 vs. 608.8 ± 203.6, p = 0.042; apico-middle turn: 410.8 ± 163.8 vs. 514.5 ± 186.3, p = 0.037). There were no significant differences in the T1 relaxation time and PD between the affected and unaffected ears (p > 0.05). Additionally, three patients without asymmetric signal intensity on conventional MRI showed asymmetric increased signal intensity in the affected ear on SyFLAIR.

CONCLUSIONS: The T2 relaxation time was significantly shorter in the affected than in the unaffected cochlea of patients with idiopathic SSNHL. The SyMRI-derived T2 relaxation time may be a promising imaging marker, suggesting that the changes in inner ear fluid composition are implicated in the idiopathic SSNHL development.

KEY POINTS: • T2 relaxation time was significantly lower in the affected than in the unaffected cochlea. • SyFLAIR showed increased lesion conspicuity compared to conventional 3D-FLAIR in detecting asymmetric high signal intensity of the affected side. • SyMRI-derived T2 relaxation time may be a promising imaging marker of the affected ear in patients with idiopathic SSNHL.

PMID:33609144 | DOI:10.1007/s00330-021-07749-5

SOURCE:
European radiology

PUBLISHER:

PMID:
pubmed:33609144

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33609144

DOI:
10.1007/s00330-021-07749-5

DATE – PUBLISHED:
Sat, 20 Feb 2021 06:00:00 -0500

DATE – DOI:
2021-02-20T17:19:51Z

DATE – ADDED:
02/21/21 01:27AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33609144/

LINK – DOI:
https://doi.org/10.1007/s00330-021-07749-5

LINK – PUBLISHER:
http://link.springer.com/10.1007/s00330-021-07749-5

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-02-21T06:27:26+00:00, https://www.hearinglosstreatmentreport.com.

https://www.nature.com/articles/s41598-020-79946-z

Steady streaming as a method for drug delivery to the inner ear

https://www.mdpi.com/1422-0067/22/1/131/htm

https://pubmed.ncbi.nlm.nih.gov/33374462/

Molecular Aspects of the Development and Function of Auditory Neurons

CATEGORY:
Research

SCREENSHOT:

TITLE:
Weakening of Interaction Networks with Aging in Tip-Link Protein Induces Hearing Loss

CONTENT:
Biochem J. 2020 Dec 3:BCJ20200799. doi: 10.1042/BCJ20200799. Online ahead of print.

ABSTRACT

Age-related hearing loss (ARHL) is a common condition in humans marking the gradual decrease in hearing with age. Perturbations in the tip-link protein cadherin-23 that absorbs the mechanical tension from sound and maintains the integrity of hearing is associated with ARHL. Here, in search of molecular origins for ARHL, we dissect the conformational behavior of cadherin-23 along with the mutant S47P that progresses the hearing-loss drastically. Using an array of experimental and computational approaches, we highlight a lower thermodynamic stability, significant weakening in the hydrogen-bond network and inter-residue correlations among β-strands, due to the S47P mutation. The loss in correlated motions translates to not only a remarkable two orders of magnitude slower folding in the mutant but also to a proportionately complex unfolding mechanism. We thus propose that loss in correlated motions within cadherin-23 with aging may trigger ARHL, a molecular feature that likely holds true for other disease-mutations in β-strand-rich proteins.

PMID:33270084 | DOI:10.1042/BCJ20200799

SOURCE:
The Biochemical journal

PUBLISHER:

PMID:
pubmed:33270084

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33270084

DOI:
10.1042/BCJ20200799

DATE – PUBLISHED:
Thu, 03 Dec 2020 06:00:00 -0500

DATE – DOI:
2020-12-03T14:31:41Z

DATE – ADDED:
12/03/20 08:09PM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33270084/

LINK – DOI:
https://doi.org/10.1042/BCJ20200799

LINK – PUBLISHER:
https://portlandpress.com/biochemj/article/doi/10.1042/BCJ20200799/227128/Weakening-of-Interaction-Networks-with-Aging-in

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2020-12-04T01:09:05+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

SCREENSHOT:

TITLE:
BRAF inhibition protects against hearing loss in mice

CONTENT:
Sci Adv. 2020 Dec 2;6(49):eabd0561. doi: 10.1126/sciadv.abd0561. Print 2020 Dec.

ABSTRACT

Hearing loss caused by noise, aging, antibiotics, and chemotherapy affects 10% of the world population, yet there are no Food and Drug Administration (FDA)-approved drugs to prevent it. Here, we screened 162 small-molecule kinase-specific inhibitors for reduction of cisplatin toxicity in an inner ear cell line and identified dabrafenib (TAFINLAR), a BRAF kinase inhibitor FDA-approved for cancer treatment. Dabrafenib and six additional kinase inhibitors in the BRAF/MEK/ERK cellular pathway mitigated cisplatin-induced hair cell death in the cell line and mouse cochlear explants. In adult mice, oral delivery of dabrafenib repressed ERK phosphorylation in cochlear cells, and protected from cisplatin- and noise-induced hearing loss. Full protection was achieved in mice with co-treatment with oral AZD5438, a CDK2 kinase inhibitor. Our study explores a previously unidentified cellular pathway and molecular target BRAF kinase for otoprotection and may advance dabrafenib into clinics to benefit patients with cisplatin- and noise-induced ototoxicity.

PMID:33268358 | DOI:10.1126/sciadv.abd0561

SOURCE:
Science advances

PUBLISHER:

PMID:
pubmed:33268358

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33268358

DOI:
10.1126/sciadv.abd0561

DATE – PUBLISHED:
Thu, 03 Dec 2020 06:00:00 -0500

DATE – DOI:
2020-12-03T02:03:28Z

DATE – ADDED:
12/03/20 07:55AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33268358/

LINK – DOI:
https://doi.org/10.1126/sciadv.abd0561

LINK – PUBLISHER:
https://advances.sciencemag.org/lookup/doi/10.1126/sciadv.abd0561

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2020-12-03T12:55:04+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

SCREENSHOT:

TITLE:
Mutations of MAP1B encoding a microtubule-associated phosphoprotein cause sensorineural hearing loss

CONTENT:
JCI Insight. 2020 Dec 3;5(23):136046. doi: 10.1172/jci.insight.136046.

ABSTRACT

The pathophysiology underlying spiral ganglion cell defect-induced deafness remains elusive. Using the whole exome sequencing approach, in combination with functional assays and a mouse disease model, we identified the potentially novel deafness-causative MAP1B gene encoding a highly conserved microtubule-associated protein. Three novel heterozygous MAP1B mutations (c.4198A>G, p.1400S>G; c.2768T>C, p.923I>T; c.5512T>C, p.1838F>L) were cosegregated with autosomal dominant inheritance of nonsyndromic sensorineural hearing loss in 3 unrelated Chinese families. Here, we show that MAP1B is highly expressed in the spiral ganglion neurons in the mouse cochlea. Using otic sensory neuron-like cells, generated by pluripotent stem cells from patients carrying the MAP1B mutation and control subject, we demonstrated that the p.1400S>G mutation caused the reduced levels and deficient phosphorylation of MAP1B, which are involved in the microtubule stability and dynamics. Strikingly, otic sensory neuron-like cells exhibited disturbed dynamics of microtubules, axonal elongation, and defects in electrophysiological properties. Dysfunctions of these derived otic sensory neuron-like cells were rescued by genetically correcting MAP1B mutation using CRISPR/Cas9 technology. Involvement of MAP1B in hearing was confirmed by audiometric evaluation of Map1b heterozygous KO mice. These mutant mice displayed late-onset progressive sensorineural hearing loss that was more pronounced in the high frequencies. The spiral ganglion neurons isolated from Map1b mutant mice exhibited the deficient phosphorylation and disturbed dynamics of microtubules. Map1b deficiency yielded defects in the morphology and electrophysiology of spiral ganglion neurons, but it did not affect the morphologies of cochlea in mice. Therefore, our data demonstrate that dysfunctions of spiral ganglion neurons induced by MAP1B deficiency caused hearing loss.

PMID:33268592 | DOI:10.1172/jci.insight.136046

SOURCE:
JCI insight

PUBLISHER:

PMID:
pubmed:33268592

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33268592

DOI:
10.1172/jci.insight.136046

DATE – PUBLISHED:
Thu, 03 Dec 2020 06:00:00 -0500

DATE – DOI:
2020-12-02T16:04:40Z

DATE – ADDED:
12/03/20 07:55AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33268592/

LINK – DOI:
https://doi.org/10.1172/jci.insight.136046

LINK – PUBLISHER:
https://insight.jci.org/articles/view/136046

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2020-12-03T12:55:03+00:00, https://www.hearinglosstreatmentreport.com.

TITLE:
Endoscopic-Assisted Drug Delivery for Inner Ear Regeneration

DESCRIPTION:
Sensorineural hearing loss is caused by irreversible loss of auditory hair cells and/or neurons and is increasing in prevalence. Hair cells and neurons do not regenerate after damage, but novel regeneration therapies based on small molecule drugs, gene therapy, and cell replacement strategies offer promising therapeutic options. Endogenous and exogenous regeneration techniques are discussed in context of their feasibility for hair cell and neuron regeneration. Gene therapy and treatment of…

CONTENT:
Otolaryngol Clin North Am . 2021 Feb;54(1):189-200. doi: 10.1016/j.otc.2020.09.022.

ABSTRACT

Sensorineural hearing loss is caused by irreversible loss of auditory hair cells and/or neurons and is increasing in prevalence. Hair cells and neurons do not regenerate after damage, but novel regeneration therapies based on small molecule drugs, gene therapy, and cell replacement strategies offer promising therapeutic options. Endogenous and exogenous regeneration techniques are discussed in context of their feasibility for hair cell and neuron regeneration. Gene therapy and treatment of synaptopathy represent promising future therapies. Minimally invasive endoscopic ear surgery offers a viable approach to aid in delivery of pharmacologic compounds, cells, or viral vectors to the inner ear for all of these techniques.

PMID:33243375 | DOI:10.1016/j.otc.2020.09.022

IDENTIFIER:
pmid:33243375,doi:10.1016/j.otc.2020.09.022

PMID:
pubmed:33243375

ID:
5aa6076e0127310720e03f8fa09545b5pubmed:33243375

DOI:
10.1016/j.otc.2020.09.022

DATE – PUBLISHED:
Fri, 27 Nov 2020 06:00:00 -0500

DATE – DOI:
2020-11-23T09:13:42Z

DATE – RETRIEVED:
11/27/20 06:17AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33243375/

LINK – DOI:
https://doi.org/10.1016/j.otc.2020.09.022

LINK – PUBLISHER:
https://linkinghub.elsevier.com/retrieve/pii/S0030666520366962

https://www.pnas.org/content/early/2020/11/13/2016858117

Proc Natl Acad Sci U S A
2020 Nov 16;202016858. doi: 10.1073/pnas.2016858117. Online ahead of print.
Fast recovery of disrupted tip links induced by mechanical displacement of hair bundles

CATEGORY:
Research

SCREENSHOT:

TITLE:
Analysis of related factors between sudden sensorineural hearing loss and serum indices base on artificial intelligence and big data

CONTENT:
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2020 Nov;34(11):977-980. doi: 10.13201/j.issn.2096-7993.2020.11.004.

ABSTRACT

Objective: The etiology and pathophysiologic mechanism of sudden sensorineural hearing loss are undefined. We will use artificial intelligence and big data methods to explore the correlation between sudden sensorineural hearing loss and serum indices. Method: A total of 1218 patients with sudden deafness admitted to Sun Yat-sen Memorial Hospital were selected as the experimental group, 95 861 healthy subjects were randomly selected as the control group at the same period. Serum biochemical indexes in two groups were collected and analyzed by TreeNet and CART machine learning algorithms, to screen out highly correlated indicators with sudden sensorineural hearing loss and dig out a set of clinical features for people with high risk of sudden sensorineural hearing loss. Result: It was found that high prevalence rate of sudden sensorineural hearing loss is related to eosinophils, reticulocyte and fibrinogen. The areas under the receiver operator characteristic curves（ROC-AUC） were exploited to evaluate the prediction performance of TreeNet model. Overall the TreeNet model has provided high predictive ability by ROC curve, achieving AUC of 0.99, both recall and accuracy rate of 99.90%. Conclusion: There is significant difference between sudden deadness and normal people in serum biochemical indexes. Eosinophil is the first important indicator to distinguish sudden sensorineural hearing loss. Treenet model has important referenced significance for the screening and diagnosis of sudden sensorineural hearing loss.

PMID:33254313 | DOI:10.13201/j.issn.2096-7993.2020.11.004

SOURCE:
Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology, head, and neck surgery

PUBLISHER:
基于人工智能下突发性聋与血清指标的相关因素分析

PMID:
pubmed:33254313

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33254313

DOI:
10.13201/j.issn.2096-7993.2020.11.004

DATE – PUBLISHED:
Mon, 30 Nov 2020 06:00:00 -0500

DATE – DOI:
2020-10-27T07:21:43Z

DATE – ADDED:
12/01/20 05:32AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33254313/

LINK – DOI:
https://doi.org/10.13201/j.issn.2096-7993.2020.11.004

LINK – PUBLISHER:
http://kns.cnki.net/kcms/detail/detail.aspx?doi=10.13201/j.issn.2096-7993.2020.11.004

IMAGE:
https://piccache.cnki.net/kdn/index/kns7/nimages/logo_xl.png

https://kns.cnki.net/kcms/Detail/resource/gb/images/icon-qrcode-download.jpg,https://kns.cnki.net/kcms/Detail/resource/gb/images/icon-pop-sample.jpg,https://piccache.cnki.net/kdn/index/kns7/nimages/logo_xl.png,https://piccache.cnki.net/kdn/index/kns7/nimages/logo_tx.png,https://piccache.cnki.net/kdn/index/kns7/nimages/foot-logo.png,https://piccache.cnki.net/kdn/index/kns7/nimages/kxwz.jpg

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2020-12-01T10:32:32+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

SCREENSHOT:

TITLE:
Outcome of otolith organ function after treatment of sudden sensorineural hearing loss

CONTENT:
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2020 Nov;34(11):993-998. doi: 10.13201/j.issn.2096-7993.2020.11.008.

ABSTRACT

Objective: This study aimed to assess the clinical practice value of ocular vestibular evoked myogenic potential（oVEMP） and cervical vestibular evoked myogenic potential（cVEMP） in monitoring the rehabilitation of vestibular function in patients with suddensen sorineural hearing loss（SSHL）. Method: Twenty-four patients with SSHL were retrospectively enrolled， showing no VEMP response on the affected side but exhibiting VEMP responses after therapies We analyzed the improvement and the restoration of hearing and the parameters of VEMP response. Result: After treatment, seven patients showed VEMP recovery, including three cases with both oVEMP and cVEMP recovery, three cases with oVEMP recovery, and one case with cVEMP recovery. Between VEMP recoved group and VEMP unrecoved group, before treatment, no significant difference was found in the thresholds of pure-tone audiometry（PTA）. However, after treatment, VEMP recoved group exhibited lower PTA thresholds and better PTA shift （P <0.01）. Multivariate analysis revealed that recovery of VEMP was the independent risk factor for the therapeutic effect of SSHL. Conclusion: The Combination of oVEMP and cVEMP is an objective tool for assessing vestibular otolithic end organ function during dynamic functional recovery in SSHL and the recovery of VEMP could predict the auditory improvement. PMID:33254317 | DOI:10.13201/j.issn.2096-7993.2020.11.008 SOURCE: Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology, head, and neck surgery PUBLISHER: 突发性聋治疗后耳石器功能转归 PMID: pubmed:33254317 ID: 0b58ea4968e09ff10f4e1238c494f316pubmed:33254317 DOI: 10.13201/j.issn.2096-7993.2020.11.008 DATE - PUBLISHED: Mon, 30 Nov 2020 06:00:00 -0500 DATE - DOI: 2020-10-27T07:21:43Z DATE - ADDED: 12/01/20 05:32AM LINK - PUBMED: https://pubmed.ncbi.nlm.nih.gov/33254317/ LINK - DOI: https://doi.org/10.13201/j.issn.2096-7993.2020.11.008 LINK - PUBLISHER: http://kns.cnki.net/kcms/detail/detail.aspx?doi=10.13201/j.issn.2096-7993.2020.11.008 IMAGE: https://piccache.cnki.net/kdn/index/kns7/nimages/logo_xl.png https://kns.cnki.net/kcms/Detail/resource/gb/images/icon-qrcode-download.jpg,https://kns.cnki.net/kcms/Detail/resource/gb/images/icon-pop-sample.jpg,https://piccache.cnki.net/kdn/index/kns7/nimages/logo_xl.png,https://piccache.cnki.net/kdn/index/kns7/nimages/logo_tx.png,https://piccache.cnki.net/kdn/index/kns7/nimages/foot-logo.png,https://piccache.cnki.net/kdn/index/kns7/nimages/kxwz.jpg REFERENCE: Hearing Loss Treatment Report, Urgent Research, 2020-12-01T10:32:34+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

TITLE:
Perspectives on Human Hearing Loss, Cochlear Regeneration, and the Potential for Hearing Restoration Therapies

DESCRIPTION:
Most adults who acquire hearing loss find it to be a disability that is poorly corrected by current prosthetics. This gap drives current research in cochlear mechanosensory hair cell regeneration and in hearing restoration. Birds and fish can spontaneously regenerate lost hair cells through a process that has become better defined in the last few years. Findings from these studies have informed new research on hair cell regeneration in the mammalian cochlea. Hair cell regeneration is one part of…

CONTENT:
Brain Sci. 2020 Oct 20;10(10):E756. doi: 10.3390/brainsci10100756.

ABSTRACT

Most adults who acquire hearing loss find it to be a disability that is poorly corrected by current prosthetics. This gap drives current research in cochlear mechanosensory hair cell regeneration and in hearing restoration. Birds and fish can spontaneously regenerate lost hair cells through a process that has become better defined in the last few years. Findings from these studies have informed new research on hair cell regeneration in the mammalian cochlea. Hair cell regeneration is one part of the greater problem of hearing restoration, as hearing loss can stem from a myriad of causes. This review discusses these issues and recent findings, and places them in the greater social context of need and community.

PMID:33092183 | DOI:10.3390/brainsci10100756

SOURCE:
Brain sciences

DATE – PUBLISHED:
20 Oct 2020

DATE – ADDED:
Fri, 23 Oct 2020 06:00:00 -0400

DATE – FOUND:
10/23/20 07:18AM

PUBMED ID:
pubmed:33092183

DOI:
10.3390/brainsci10100756

PUBMED LINK:
https://pubmed.ncbi.nlm.nih.gov/33092183/

DOI LINK:
https://doi.org/10.3390/brainsci10100756

PUBLISHER LINK:
https://www.mdpi.com/2076-3425/10/10/756

CATEGORY:
Research

TITLE:
Altered outer hair cell mitochondrial and subsurface cisternae connectomics are candidate mechanisms for hearing-loss in mice

DESCRIPTION:
Organelle crosstalk is vital for cellular functions. The propinquity of mitochondria, endoplasmic reticulum (ER), and plasma membrane promote regulation of multiple functions, which include intracellular Ca^(2+) flux, and cellular biogenesis. Although the purposes of apposing mitochondria and ER have been described, an understanding of altered organelle connectomics related to disease states is emerging. Since inner ear outer hair cell (OHC) degeneration is a common trait of age-related hearing…

CONTENT:
J Neurosci. 2020 Oct 5:JN-RM-2901-19. doi: 10.1523/JNEUROSCI.2901-19.2020. Online ahead of print.

ABSTRACT

Organelle crosstalk is vital for cellular functions. The propinquity of mitochondria, endoplasmic reticulum (ER), and plasma membrane promote regulation of multiple functions, which include intracellular Ca2+ flux, and cellular biogenesis. Although the purposes of apposing mitochondria and ER have been described, an understanding of altered organelle connectomics related to disease states is emerging. Since inner ear outer hair cell (OHC) degeneration is a common trait of age-related hearing loss, the objective of this study was to investigate whether the structural and functional coupling of mitochondria with subsurface cisternae (SSC), was affected by aging. We applied functional and structural probes to equal numbers of male and female mice with a hearing phenotype akin to human aging. We discovered the polarization of cristae and crista junctions in mitochondria tethered to the SSC in OHCs. Aging was associated with SSC stress and decoupling of mitochondria with the SSC, mitochondrial fission/fusion imbalance, a remarkable reduction in mitochondrial and cytoplasmic Ca2+ levels, reduced K+ -induced Ca2+ uptake, and marked plasticity of cristae membranes. A model of structure-based ATP production predicts profound energy stress in older OHCs. This report provides data suggesting that altered membrane organelle connectomics may result in progressive hearing loss.SIGNIFICANCE STATEMENT We address the question, “Do aged OHCs exhibit detectable changes in organelle connectomics that would help us better understand human hearing loss in a relevant mouse model?” Because of the close association of mitochondria SSC over much of the OHC inner surface, mitochondria-SSC connectomics appears to play a central role in hearing. In polarized cells such as OHCs, where there is functional segregation of apical versus basal regions, the relationship between altered organelle connectomics and hearing loss is unknown. We propose a mechanism of mitochondria-SSC dysregulation related to aging and OHC degeneration, showing distinct altered mitochondrial and cytoplasmic Ca2+ regulation, mitochondrial polarization, and fission/fusion imbalance, mitochondrial-SSC decoupling, and SSC and cellular energy stress.

PMID:33020216 | DOI:10.1523/JNEUROSCI.2901-19.2020

SOURCE:
The Journal of neuroscience : the official journal of the Society for Neuroscience

DATE – PUBLISHED:
5 Oct 2020

DATE – ADDED:
Tue, 06 Oct 2020 06:00:00 -0400

DATE – FOUND:
10/06/20 07:06AM

PUBMED ID:
pubmed:33020216

DOI:
10.1523/JNEUROSCI.2901-19.2020

PUBMED LINK:
https://pubmed.ncbi.nlm.nih.gov/33020216/

DOI LINK:
https://doi.org/10.1523/JNEUROSCI.2901-19.2020

PUBLISHER LINK:
http://www.jneurosci.org/lookup/doi/10.1523/JNEUROSCI.2901-19.2020

CATEGORY:
Research

TITLE:
Biomarkers Suggesting Favorable Prognostic Outcomes in Sudden Sensorineural Hearing Loss

DESCRIPTION:
Sudden sensorineural hearing loss (SSNHL) is a medical emergency, making detailed examination to determine possible causes and early treatment important. However, etiological examinations in SSNHL do not always reveal a cause, and several factors have been found to affect treatment outcomes. Various studies are being performed to determine the prognosis and effects of treatment in patients who experience sudden hearing loss, and to identify biomarkers associated with this condition. Embase,…

CONTENT:
Int J Mol Sci. 2020 Sep 30;21(19):E7248. doi: 10.3390/ijms21197248.

ABSTRACT

Sudden sensorineural hearing loss (SSNHL) is a medical emergency, making detailed examination to determine possible causes and early treatment important. However, etiological examinations in SSNHL do not always reveal a cause, and several factors have been found to affect treatment outcomes. Various studies are being performed to determine the prognosis and effects of treatment in patients who experience sudden hearing loss, and to identify biomarkers associated with this condition. Embase, PubMed, and the Cochrane database were searched using the key words SSNHL, prognostic, and biomarker. This search identified 4 articles in Embase, 28 articles in PubMed, and 36 in the Cochrane database. Of these 68 articles, 3 were duplicates and 37 were unrelated to the research topic. After excluding these articles, the remaining 28 articles were reviewed. Factors associated with SSNHL were divided into six categories: metabolic, hemostatic, inflammatory, immunologic, oxidative, and other factors. The associations between these factors with the occurrence of SSNHL and with patient prognosis were analyzed. Low monocyte counts, low neutrophil/lymphocyte ratio (NLR) and monocyte/high-density lipoproteins (HDL) cholesterol ratio (MHR), and low concentrations of fibrinogen, platelet glycoprotein (GP) IIIa, and TNF-α were found to be associated with good prognosis. However, these factors alone could not completely determine the onset of and recovery from SSNHL, suggesting the need for future basic and clinical studies.

PMID:33008090 | DOI:10.3390/ijms21197248

SOURCE:
International journal of molecular sciences

DATE – PUBLISHED:
30 Sep 2020

DATE – ADDED:
Sat, 03 Oct 2020 06:00:00 -0400

DATE – FOUND:
10/04/20 02:17AM

PUBMED ID:
pubmed:33008090

DOI:
10.3390/ijms21197248

PUBMED LINK:
https://pubmed.ncbi.nlm.nih.gov/33008090/

DOI LINK:
https://doi.org/10.3390/ijms21197248

PUBLISHER LINK:
https://www.mdpi.com/1422-0067/21/19/7248
https://www.mdpi.com/1422-0067/21/19/7248/htm

CATEGORY:
Research

TITLE:
Altered Brain Activity and Functional Connectivity in Unilateral Sudden Sensorineural Hearing Loss

DESCRIPTION:
CONCLUSION: SSNHL causes functional alterations in brain regions, mainly in the striatum, auditory cortex, visual cortex, MTG, AG, precuneus, and limbic lobes within the acute period of hearing loss.

CONTENT:
Neural Plast. 2020 Sep 22;2020:9460364. doi: 10.1155/2020/9460364. eCollection 2020.

ABSTRACT

BACKGROUND: Sudden sensorineural hearing loss (SSNHL) is an otologic emergency and could lead to social difficulties and mental disorders in some patients. Although many studies have analyzed altered brain function in populations with hearing loss, little information is available about patients with idiopathic SSNHL. This study is aimed at investigating brain functional changes in SSNHL via functional magnetic resonance imaging (fMRI).

METHODS: Thirty-six patients with SSNHL and thirty well-matched normal hearing individuals underwent resting-state fMRI. Amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), and functional connectivity (FC) values were calculated.

RESULTS: In the SSNHL patients, ALFF and fALFF were significantly increased in the bilateral putamen but decreased in the right calcarine cortex, right middle temporal gyrus (MTG), and right precentral gyrus. Widespread increases in FC were observed between brain regions, mainly including the bilateral auditory cortex, bilateral visual cortex, left striatum, left angular gyrus (AG), bilateral precuneus, and bilateral limbic lobes in patients with SSNHL. No decreased FC was observed.

CONCLUSION: SSNHL causes functional alterations in brain regions, mainly in the striatum, auditory cortex, visual cortex, MTG, AG, precuneus, and limbic lobes within the acute period of hearing loss.

PMID:33029130 | PMC:PMC7527900 | DOI:10.1155/2020/9460364

SOURCE:
Neural plasticity

DATE – PUBLISHED:
22 Sep 2020

DATE – ADDED:
Thu, 08 Oct 2020 06:00:00 -0400

DATE – FOUND:
10/08/20 06:42AM

PUBMED ID:
pubmed:33029130

DOI:
10.1155/2020/9460364

PUBMED LINK:
https://pubmed.ncbi.nlm.nih.gov/33029130/

DOI LINK:
https://doi.org/10.1155/2020/9460364

PUBLISHER LINK:
https://www.hindawi.com/journals/np/2020/9460364/

https://link.springer.com/article/10.1007/s12035-020-02092-0

Combined Atoh1 and Neurod1 Deletion Reveals Autonomous Growth of Auditory Nerve Fibers

https://journals.sagepub.com/doi/10.1177/0145561320952501

https://www.ncbi.nlm.nih.gov/pubmed/32865463?dopt=Abstract

Related Articles

The Role of Anti-Endothelial Cell Autoantibodies and Immune Response in Acute Low-Tone Hearing Loss.

Ear Nose Throat J. 2020 Aug 31;:145561320952501

Authors: Chen D, Wang Z, Jia G, Mao H, Ni Y

Abstract

OBJECTIVE: Immunity is associated with acute low tone hearing loss. However, the exact pathophysiology of immunity-mediated acute low tone hearing loss remains unknown. In this study, we evaluated the presence, therapeutic effectiveness, and immunopathological mechanisms of anti-endothelial cell autoantibodies (AECEs) in patients with acute low-frequency hearing loss.

MATERIAL AND METHODS: Forty-nine patients who were treated as inpatients having acute low-frequency hearing loss and additional symptoms, such as ear fullness, tinnitus, dizziness, or hyperacusis, were enrolled in this study. Serum samples from these patients were collected for laboratory serum autoimmunity detection, including AECAs, antinuclear antibodies, immunoglobulin, and circular immune complex. Therapeutic responses to combination therapy in short-term outcome and serum cytokine levels were compared between AECA-positive and AECA-negative patients.

RESULTS: Anti-endothelial cell autoantibodies-positive patients tended to show significantly less response to standard therapy compared with AECAs controls (P < .05). Moreover, some serum cytokine levels elevated in both AECAs- and AECAs+ groups. Positive ratio of interleukin-8 and concentrations of macrophage inflammatory protein-1α were found higher in AECAs+ groups (P < .05). CONCLUSION: The results supported that AECAs might wield influence on the short-term outcome of acute low-tone hearing loss (ALHL) treatment. Furthermore, AECA-mediated acute low-frequency hearing loss possibly involved dysregulation of inflammation process and release of cytokines. PMID: 32865463 [PubMed - as supplied by publisher]

CATEGORY:
Research

TITLE:
Systematic Transcriptome Analysis of Noise-Induced Hearing Loss Pathogenesis Suggests Inflammatory Activities and Multiple Susceptible Molecules and Pathways

DESCRIPTION:
Noise-induced hearing loss (NIHL) is characterized by damage to cochlear neurons and associated hair cells; however, a systematic evaluation of NIHL pathogenesis is still lacking. Here, we systematically evaluated differentially expressed genes of 22 cochlear samples in an NIHL mouse model. We performed Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and weighted gene co-expression network analysis (WGCNA). Core modules were detected using protein-protein interactions…

CONTENT:
Front Genet. 2020 Aug 28;11:968. doi: 10.3389/fgene.2020.00968. eCollection 2020.

ABSTRACT

Noise-induced hearing loss (NIHL) is characterized by damage to cochlear neurons and associated hair cells; however, a systematic evaluation of NIHL pathogenesis is still lacking. Here, we systematically evaluated differentially expressed genes of 22 cochlear samples in an NIHL mouse model. We performed Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and weighted gene co-expression network analysis (WGCNA). Core modules were detected using protein-protein interactions and WGCNA with functional annotation, diagnostic value evaluation, and experimental validation. Pooled functional annotation suggested the involvement of multiple inflammatory pathways, including the TNF signaling pathway, IL-17 signaling pathway, NF-kappa B signaling pathway, rheumatoid arthritis, and p53 signaling pathway. The core modules suggested that responses to cytokines, heat, cAMP, ATP, mechanical stimuli, and immune responses were important in NIHL pathogenesis. These activities primarily occurred on the external side of the plasma membrane, the extracellular region, and the nucleus. Binding activities, including CCR2 receptor binding, protein binding, and transcription factor binding, may be important. Additionally, the hub molecules with diagnostic value included Relb, Hspa1b, Ccl2, Ptgs2, Ldlr, Plat, and Ccl17. An evaluation of Relb and Hspa1b protein levels showed that Relb was upregulated in spiral ganglion neurons, which might have diagnostic value. In conclusion, this study indicates that the inflammatory response is involved in auditory organ changes in NIHL pathogenesis; moreover, several molecules and activities have essential and subtle influences that have translational potential for pharmacological intervention.

PMID:33005175 | PMC:PMC7483666 | DOI:10.3389/fgene.2020.00968

SOURCE:
Frontiers in genetics

DATE – PUBLISHED:
28 Aug 2020

DATE – ADDED:
Fri, 02 Oct 2020 06:00:00 -0400

DATE – FOUND:
10/02/20 07:34AM

PUBMED ID:
pubmed:33005175

DOI:
10.3389/fgene.2020.00968

PUBMED LINK:
https://pubmed.ncbi.nlm.nih.gov/33005175/

DOI LINK:
https://doi.org/10.3389/fgene.2020.00968

PUBLISHER LINK:
https://www.frontiersin.org/article/10.3389/fgene.2020.00968/full

https://www.tandfonline.com/doi/abs/10.1080/17460441.2020.1806232?journalCode=iedc20

https://pubmed.ncbi.nlm.nih.gov/32838572/

Drug development for noise-induced hearing loss
Isabel Varela-Nieto ,Silvia Murillo-Cuesta,Miryam Calvino,Rafael Cediel &Luis Lassaletta
Received 23 Mar 2020, Accepted 03 Aug 2020, Published online: 25 Aug 2020
Download citation https://doi.org/10.1080/17460441.2020.1806232 CrossMark LogoCrossMark

https://www.pnas.org/content/early/2020/08/20/2000417117

https://pubmed.ncbi.nlm.nih.gov/32826333/

RESEARCH ARTICLE
LIN28B/let-7 control the ability of neonatal murine auditory supporting cells to generate hair cells through mTOR signaling
Xiao-Jun Li and View ORCID ProfileAngelika Doetzlhofer
PNAS first published August 21, 2020 https://doi.org/10.1073/pnas.2000417117

https://advances.sciencemag.org/content/6/33/eabb4922

Decades-old model of slow adaptation in sensory hair cells is not supported in mammals
View ORCID ProfileGiusy A. Caprara1, View ORCID ProfileAndrew A. Mecca1,2 and View ORCID ProfileAnthony W. Peng1,*
See all authors and affiliations

Science Advances 14 Aug 2020:
Vol. 6, no. 33, eabb4922
DOI: 10.1126/sciadv.abb4922

https://www.ncbi.nlm.nih.gov/pubmed/32681786?dopt=Abstract

Cochlear synaptopathy: new findings in animal and human research.

Rev Neurosci. 2020 Jul 20;:

Authors: Aedo C, Aguilar E

Abstract

In animal models, prolonged exposure (2 h) to high-level noise causes an irreparable damage to the synapses between the inner hair cells and auditory nerve fibers within the cochlea. Nevertheless, this injury does not necessarily alter the hearing threshold. Similar findings have been observed as part of typical aging in animals. This type of cochlear synaptopathy, popularly called “hidden hearing loss,” has been a significant issue in neuroscience research and clinical audiology scientists. The results obtained in different investigations are inconclusive in their diagnosis and suggest new strategies for both prognosis and treatment of cochlear synaptopathy. Here we review the major physiological findings regarding cochlear synaptopathy in animals and humans and discuss mathematical models. We also analyze the potential impact of these results on clinical practice and therapeutic options.

PMID: 32681786 [PubMed – as supplied by publisher]