scholarly journals Evidence for a dynorphin-mediated inner ear immune/inflammatory response and glutamate-induced neural excitotoxicity: an updated analysis

2019 ◽  
Vol 122 (4) ◽  
pp. 1421-1460
Author(s):  
Tony L. Sahley ◽  
David J. Anderson ◽  
Michael D. Hammonds ◽  
Karthik Chandu ◽  
Frank E. Musiek
Keyword(s):  
Hearing Loss ◽  
Brain Stem ◽  
Inner Ear ◽  
Hair Cells ◽  
Oxidative Stress Response ◽  
Neural Systems ◽  
Type I ◽  
Excitatory Neurotransmitter ◽  
Axon Terminals ◽  
Cochlear Hearing Loss

Acoustic overstimulation (AOS) is defined as the stressful overexposure to high-intensity sounds. AOS is a precipitating factor that leads to a glutamate (GLU)-induced Type I auditory neural excitotoxicity and an activation of an immune/inflammatory/oxidative stress response within the inner ear, often resulting in cochlear hearing loss. The dendrites of the Type I auditory neural neurons that innervate the inner hair cells (IHCs), and respond to the IHC release of the excitatory neurotransmitter GLU, are themselves directly innervated by the dynorphin (DYN)-bearing axon terminals of the descending brain stem lateral olivocochlear (LOC) system. DYNs are known to increase GLU availability, potentiate GLU excitotoxicity, and induce superoxide production. DYNs also increase the production of proinflammatory cytokines by modulating immune/inflammatory signal transduction pathways. Evidence is provided supporting the possibility that the GLU-mediated Type I auditory neural dendritic swelling, inflammation, excitotoxicity, and cochlear hearing loss that follow AOS may be part of a brain stem-activated, DYN-mediated cascade of inflammatory events subsequent to a LOC release of DYNs into the cochlea. In support of a DYN-mediated cascade of events are established investigations linking DYNs to the immune/inflammatory/excitotoxic response in other neural systems.

scholarly journals Inner Ear and Muscle Developmental Defects in Smpx-Deficient Zebrafish Embryos

2021 ◽  
Vol 22 (12) ◽  
pp. 6497
Author(s):  
Anna Ghilardi ◽  
Alberto Diana ◽  
Renato Bacchetta ◽  
Nadia Santo ◽  
Miriam Ascagni ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Inner Ear ◽  
Hair Cells ◽  
Muscle Fibers ◽  
Underlying Mechanism ◽  
Loss Of Function ◽  
Zebrafish Model ◽  
Developmental Defects ◽  
Inner Ear Development ◽  
Syndromic Hearing Loss

The last decade has witnessed the identification of several families affected by hereditary non-syndromic hearing loss (NSHL) caused by mutations in the SMPX gene and the loss of function has been suggested as the underlying mechanism. In the attempt to confirm this hypothesis we generated an Smpx-deficient zebrafish model, pointing out its crucial role in proper inner ear development. Indeed, a marked decrease in the number of kinocilia together with structural alterations of the stereocilia and the kinocilium itself in the hair cells of the inner ear were observed. We also report the impairment of the mechanotransduction by the hair cells, making SMPX a potential key player in the construction of the machinery necessary for sound detection. This wealth of evidence provides the first possible explanation for hearing loss in SMPX-mutated patients. Additionally, we observed a clear muscular phenotype consisting of the defective organization and functioning of muscle fibers, strongly suggesting a potential role for the protein in the development of muscle fibers. This piece of evidence highlights the need for more in-depth analyses in search for possible correlations between SMPX mutations and muscular disorders in humans, thus potentially turning this non-syndromic hearing loss-associated gene into the genetic cause of dysfunctions characterized by more than one symptom, making SMPX a novel syndromic gene.

Ionic Currents and Electromotility in Inner Ear Hair Cells From Humans

1998 ◽  
Vol 79 (4) ◽  
pp. 2235-2239 ◽  
Author(s):  
John S. Oghalai ◽  
Jeffrey R. Holt ◽  
Takashi Nakagawa ◽  
Thomas M. Jung ◽  
Newton J. Coker ◽  
...  
Keyword(s):  
Inner Ear ◽  
Hair Cells ◽  
Ionic Currents ◽  
Sensory Epithelium ◽  
Outer Hair Cells ◽  
Sensory Receptor ◽  
Surgical Removal ◽  
Type I ◽  
Vestibular Hair Cells ◽  
Sensory Receptor Cells

Oghalai, John S., Jeffrey R. Holt, Takashi Nakagawa, Thomas M. Jung, Newton J. Coker, Herman A. Jenkins, Ruth Anne Eatock, and William E. Brownell. Ionic currents and electromotility in inner ear hair cells from humans. J. Neurophysiol. 79: 2235–2239, 1998. The upright posture and rich vocalizations of primates place demands on their senses of balance and hearing that differ from those of other animals. There is a wealth of behavioral, psychophysical, and CNS measures characterizing these senses in primates, but no prior recordings from their inner ear sensory receptor cells. We harvested human hair cells from patients undergoing surgical removal of life-threatening brain stem tumors and measured their ionic currents and electromotile responses. The hair cells were either isolated or left in situ in their sensory epithelium and investigated using the tight-seal, whole cell technique. We recorded from both type I and type II vestibular hair cells under voltage clamp and found four voltage-dependent currents, each of which has been reported in hair cells of other animals. Cochlear outer hair cells demonstrated electromotility in response to voltage steps like that seen in rodent animal models. Our results reveal many qualitative similarities to hair cells obtained from other animals and justify continued investigations to explore quantitative differences that may be associated with normal or pathological human sensation.

scholarly journals Early appearance of key transcription factors influence the spatiotemporal development of the human inner ear

2019 ◽  
Vol 379 (3) ◽  
pp. 459-471 ◽  
Author(s):  
Lejo Johnson Chacko ◽  
Consolato Sergi ◽  
Theresa Eberharter ◽  
Jozsef Dudas ◽  
Helge Rask-Andersen ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Inner Ear ◽  
Hair Cells ◽  
Transforming Growth Factor ◽  
Expression Patterns ◽  
Organ Of Corti ◽  
Sensory Epithelium ◽  
Receptor Expression ◽  
Cell Phenotype ◽  
Type I

AbstractExpression patterns of transcription factors leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), transforming growth factor-β-activated kinase-1 (TAK1), SRY (sex-determining region Y)-box 2 (SOX2), and GATA binding protein 3 (GATA3) in the developing human fetal inner ear were studied between the gestation weeks 9 and 12. Further development of cochlear apex between gestational weeks 11 and 16 (GW11 and GW16) was examined using transmission electron microscopy. LGR5 was evident in the apical poles of the sensory epithelium of the cochlear duct and the vestibular end organs at GW11. Immunostaining was limited to hair cells of the organ of Corti by GW12. TAK1 was immune positive in inner hair cells of the organ of Corti by GW12 and colocalized with p75 neurotrophic receptor expression. Expression for SOX2 was confined primarily to the supporting cells of utricle at the earliest stage examined at GW9. Intense expression for GATA3 was presented in the cochlear sensory epithelium and spiral ganglia at GW9. Expression of GATA3 was present along the midline of both the utricle and saccule in the zone corresponding to the striolar reversal zone where the hair cell phenotype switches from type I to type II. The spatiotemporal gradient of the development of the organ of Corti was also evident with the apex of the cochlea forming by GW16. It seems that highly specific staining patterns of several transcriptions factors are critical in guiding the genesis of the inner ear over development. Our findings suggest that the spatiotemporal gradient in cochlear development extends at least until gestational week 16.

Audiological Study in Guinea Pigs with Type I Allergy Induced in the Inner Ear

1993 ◽  
Vol 102 (7) ◽  
pp. 537-542 ◽  
Author(s):  
Kengo Uno ◽  
Hironori Fukuda ◽  
Kenichiro Miyamura ◽  
Keisuke Masuyama ◽  
Yorinori Kanzaki ◽  
...  
Keyword(s):  
Brain Stem ◽  
Inner Ear ◽  
Guinea Pigs ◽  
Type I ◽  
Auditory Brain Stem Response ◽  
Type I Allergy ◽  
Summating Potential ◽  
Auditory Brain Stem ◽  
Brain Stem Response ◽  
Specific Challenge

Time course studies of electrocochleography and the auditory brain stem response were performed in guinea pigs that were passively sensitized by sera containing antidinitrophenyl reaginic antibody and specifically challenged by dinitrophenyl—bovine serum albumin injected through the stylomastoid foramen. A negative summating potential on electrocochleography was observed from 12 to 48 hours, but not at 72 hours, after the specific challenge. A threshold increase on the auditory brain stem response was observed 15 minutes after the specific challenge; the threshold recovered to the prechallenge level within 7 days. Further, we used Tranilast, a blocking agent of chemical mediator release from mast cells, before the specific challenge. A negative summating potential and head deviation were not observed after the use of this agent. These results suggest that the auditory change provoked in the inner ear of the sensitized guinea pig may have been induced by type I allergy.

Bilateral Evoked Otoacoustic Emissions in a Child with Bilateral Profound Hearing Loss

1996 ◽  
Vol 105 (4) ◽  
pp. 286-288 ◽  
Author(s):  
Laurence Laccourreye ◽  
Esther Tran BA Huy ◽  
Martine François ◽  
Philippe Narcy
Keyword(s):  
Computed Tomography ◽  
Hearing Loss ◽  
Brain Stem ◽  
Inner Ear ◽  
Otoacoustic Emissions ◽  
Review Of The Literature ◽  
Profound Hearing Loss ◽  
Normal Limits

Recording of bilateral evoked otoacoustic emissions in a 3-year-old girl with bilateral profound hearing loss is presented. No component of auditory-evoked brain stem potentials was recorded. Findings on computed tomography of the inner ear were within normal limits. At retest 3 months later, these results were unchanged. Explanations for this particular condition are presented together with a review of the literature.

scholarly journals Effects of Microbubble Size on Ultrasound-Mediated Gene Transfection in Auditory Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Ai-Ho Liao ◽  
Yi-Lei Hsieh ◽  
Hsin-Chiao Ho ◽  
Hang-Kang Chen ◽  
Yi-Chun Lin ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Hearing Loss ◽  
Gene Transfer ◽  
Inner Ear ◽  
Hair Cells ◽  
Gene Transfection ◽  
Effective Technique ◽  
Size Dependent ◽  
Genes Encoding

Gene therapy for sensorineural hearing loss has recently been used to insert genes encoding functional proteins to preserve, protect, or even regenerate hair cells in the inner ear. Our previous study demonstrated a microbubble- (MB-)facilitated ultrasound (US) technique for delivering therapeutic medication to the inner ear. The present study investigated whether MB-US techniques help to enhance the efficiency of gene transfection by means of cationic liposomes on HEI-OC1 auditory cells and whether MBs of different sizes affect such efficiency. Our results demonstrated that the size of MBs was proportional to the concentration of albumin or dextrose. At a constant US power density, using 0.66, 1.32, and 2.83 μm albumin-shelled MBs increased the transfection rate as compared to the control by 30.6%, 54.1%, and 84.7%, respectively; likewise, using 1.39, 2.12, and 3.47 μm albumin-dextrose-shelled MBs increased the transfection rates by 15.9%, 34.3%, and 82.7%, respectively. The results indicate that MB-US is an effective technique to facilitate gene transfer on auditory cellsin vitro. Such size-dependent MB oscillation behavior in the presence of US plays a role in enhancing gene transfer, and by manipulating the concentration of albumin or dextrose, MBs of different sizes can be produced.

scholarly journals Genetics of Nonsyndromic Congenital Hearing Loss

Scientifica ◽  
2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Oguz Kadir Egilmez ◽  
M. Tayyar Kalcioglu
Keyword(s):  
Hearing Loss ◽  
Inner Ear ◽  
Hair Cells ◽  
Neurotransmitter Release ◽  
Intracellular Transport ◽  
Autosomal Recessive ◽  
Treatment Options ◽  
The Body ◽  
Congenital Hearing Loss ◽  
Congenital Hearing Impairment

Congenital hearing impairment affects nearly 1 in every 1000 live births and is the most frequent birth defect in developed societies. Hereditary types of hearing loss account for more than 50% of all congenital sensorineural hearing loss cases and are caused by genetic mutations. HL can be either nonsyndromic, which is restricted to the inner ear, or syndromic, a part of multiple anomalies affecting the body. Nonsyndromic HL can be categorised by mode of inheritance, such as autosomal dominant (called DFNA), autosomal recessive (DFNB), mitochondrial, and X-linked (DFN). To date, 125 deafness loci have been reported in the literature: 58 DFNA loci, 63 DFNB loci, and 4 X-linked loci. Mutations in genes that control the adhesion of hair cells, intracellular transport, neurotransmitter release, ionic hemeostasis, and cytoskeleton of hair cells can lead to malfunctions of the cochlea and inner ear. In recent years, with the increase in studies about genes involved in congenital hearing loss, genetic counselling and treatment options have emerged and increased in availability. This paper presents an overview of the currently known genes associated with nonsyndromic congenital hearing loss and mutations in the inner ear.

scholarly journals Fgf8 genetic labeling reveals the early specification of vestibular hair cell type in mouse utricle

Development ◽  
2020 ◽  
Vol 147 (22) ◽  
pp. dev192849
Author(s):  
Evan M. Ratzan ◽  
Anne M. Moon ◽  
Michael R. Deans
Keyword(s):  
Hair Cell ◽  
Inner Ear ◽  
Hair Cells ◽  
Conditional Knockout ◽  
Developmental Model ◽  
Type I ◽  
Ear Development ◽  
Inner Ear Development ◽  
Morphological Criteria ◽  
Genetic Labeling

ABSTRACTFGF8 signaling plays diverse roles in inner ear development, acting at multiple stages from otic placode induction to cellular differentiation in the organ of Corti. As a secreted morphogen with diverse functions, Fgf8 expression is likely to be spatially restricted and temporally dynamic throughout inner ear development. We evaluated these characteristics using genetic labeling mediated by Fgf8mcm gene-targeted mice and determined that Fgf8 expression is a specific and early marker of Type-I vestibular hair cell identity. Fgf8mcm expression initiates at E11.5 in the future striolar region of the utricle, labeling hair cells following EdU birthdating, and demonstrates that sub-type identity is determined shortly after terminal mitosis. This early fate specification is not apparent using markers or morphological criteria that are not present before birth in the mouse. Although analyses of Fgf8 conditional knockout mice did not reveal developmental phenotypes, the restricted pattern of Fgf8 expression suggests that functionally redundant FGF ligands may contribute to vestibular hair cell differentiation and supports a developmental model in which Type-I and Type-II hair cells develop in parallel rather than from an intermediate precursor.

scholarly journals A Natural Occurring Mouse Model with Adgrv1 Mutation of Usher Syndrome 2C and Characterization of its Recombinant Inbred Strains

2018 ◽  
Vol 47 (5) ◽  
pp. 1883-1897 ◽  
Author(s):  
Weiming Yan ◽  
Pan Long ◽  
Tao Chen ◽  
Wei Liu ◽  
Lu Yao ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Inner Ear ◽  
Retinal Degeneration ◽  
Western Blotting ◽  
Hair Cells ◽  
Recombinant Inbred ◽  
Usher Syndrome ◽  
Inbred Strains ◽  
Outer Hair Cells ◽  
Recombinant Inbred Strains

Background/Aims: Our laboratory discovered a Kunming mouse with enormous electroretinogram (ERG) defects. Its auditory brainstem response (ABR) threshold was significantly elevated and closely resembled the features of Usher syndrome (USH). This study sought to cross these USH-like mice (named KMush/ush mice) with CBA/CaJ mice to establish recombinant inbred strains and identify their phenotypes and genotypes. Methods: KMush/ush mice were crossed with CBA/CaJ mice to establish inbred strains by sibling mating. ERG, ABR, ocular fundus morphology, histological examinations of the retina and inner ear, quantitative real-time polymerase chain reaction, western blotting, and exon sequencing were performed to assess the phenotypes and genotypes of the offspring strains. Results: The F1 hybrids from crossing KMush/ush and CBA/CaJ mice had normal ERG and ABR responses. The F2 offspring from intercrossing the F1 mice showed a segregation of the retinitis pigmentosa (RP) and hearing loss phenotypes. The CBA-1ush/ush mice had an RP phenotype that was characterized by a vanished ERG waveform and loss of the outer nuclear layer. Their Pde6b gene had a nonsense mutation that resulted in the failure of protein production in western blotting. However, the ABR threshold of this strain of mice was normal. The CBA-2ush/ush mice had normal retinal function and architecture. Their ABR threshold was increased, with a dramatic degeneration of the stereocilia bundles in the outer hair cells of the inner ear. Whole exome sequencing and exon sequencing revealed a deletion of one base pair in exon 31 of the Adgrv1 gene, which would result in the premature termination of protein encoding. The level of Adgrv1 mRNA was reduced in the CBA-2ush/ush mice. The CBA-3ush/ush mice had phenotypes of RP, elevated ABR threshold, and degeneration of the stereocilia bundles in the outer hair cells. They were closely associated with the nonsense mutations of Pde6b and Adgrv1, respectively. Conclusion: We isolated a mouse strain with hearing loss from inbred mice with retinal degeneration and established it as a recombinant inbred strain with a spontaneous mutation in Adgrv1, the human Usher syndrome 2C gene. The retinal degeneration was cause by a mutation in Pde6b, while the hearing loss was caused by a mutation in Adgrv1.

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