MicroRNAs Involved in Aging of the Lateral Wall of the Cochlear Duct
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ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: David He
PROVIDER: E-GEOD-57782 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Spiral ganglion neurons (SGNs) and the associated components of the auditory nerve are primary carriers of auditory information from hair cells to the brain. Loss of SGNs occurs with many pathological conditions, resulting in permanent sensorineural hearing loss. Neural stem/progenitors (NSPs) have been well-characterized in several locations of adult brain and retina. However, it is unclear whether NSPs are present in the adult auditory nerve. Here we examined the self-renewal potential of the adult auditory nerve using ouabain application as a well-established mouse model of acute SGN injury. The observed increase in cell proliferation, alteration in enchromatin/heterochromatin ratio and down-regulation of histone deacetylase expression in glial cells suggest that the quiescent glial cells convert to an activated state after SGN degeneration. This was further confirmed by global gene expression analysis of injured auditory nerves, which showed up-regulation of numerous neurogenesis- and/or development-associated genes shortly after ouabain exposure. These genes include molecular markers commonly used for the identification of NSPs. Under a strict culture regimen, auditory nerve-derived cells of adult mouse ears gave rise to neurospheres, suggesting that multipotent NSPs are present in adult cochlear nerve. Neurosphere assays on Sox2 transgenic mice revealed that Sox2+ glial cells are the source for NSPs. Our data also showed that acute injury or hypoxia enhances neurosphere formation. Taken together, our study revealed that glial cells of adult cochlea exhibit several NSP characteristics, and hence these mature non-neuronal cells may be important targets for promoting self-repair of degenerative auditory nerves. Analysis was conducted on auditory nerve samples from stages encompassing maturation and onset of hearing. Cochleas were collected from euthanized mice (CBA/CaJ) at perinatal (P) stages P0, P3, P7, P10, P14 and P21. Cochleas underwent microdissection to remove the outer bony cochlear shell and cochlear lateral wall, thus preserving the modiolus portion of cochlea which contains mainly the auditory nerve. Paired cochleas (i.e., from left and right ears) from each mouse were pooled to make individual samples. All sample types were done in experimental duplicate (n=2).
2015-04-30 | E-GEOD-59415 | biostudies-arrayexpress
Project description:Age-related hearing loss is a progressive sensorineural hearing loss that occurs as people get older. Degeneration of the organ of Corti and atrophy of the lateral wall of the cochlear duct (or scala media) in the inner ear are the two primary causes. MicroRNAs (miRNAs), a class of short non-coding RNAs that regulate the expression of mRNA/protein targets, are important regulators of cellular senescence and aging. We examined the change of miRNA gene expression profiles in the lateral wall of the cochlear duct in two mouse strains during aging
2014-10-01 | GSE57782 | GEO
Project description:Spiral ganglion neurons (SGNs) and the associated components of the auditory nerve are primary carriers of auditory information from hair cells to the brain. Loss of SGNs occurs with many pathological conditions, resulting in permanent sensorineural hearing loss. Neural stem/progenitors (NSPs) have been well-characterized in several locations of adult brain and retina. However, it is unclear whether NSPs are present in the adult auditory nerve. Here we examined the self-renewal potential of the adult auditory nerve using ouabain application as a well-established mouse model of acute SGN injury. The observed increase in cell proliferation, alteration in enchromatin/heterochromatin ratio and down-regulation of histone deacetylase expression in glial cells suggest that the quiescent glial cells convert to an activated state after SGN degeneration. This was further confirmed by global gene expression analysis of injured auditory nerves, which showed up-regulation of numerous neurogenesis- and/or development-associated genes shortly after ouabain exposure. These genes include molecular markers commonly used for the identification of NSPs. Under a strict culture regimen, auditory nerve-derived cells of adult mouse ears gave rise to neurospheres, suggesting that multipotent NSPs are present in adult cochlear nerve. Neurosphere assays on Sox2 transgenic mice revealed that Sox2+ glial cells are the source for NSPs. Our data also showed that acute injury or hypoxia enhances neurosphere formation. Taken together, our study revealed that glial cells of adult cochlea exhibit several NSP characteristics, and hence these mature non-neuronal cells may be important targets for promoting self-repair of degenerative auditory nerves. Adult Mice (CBA/CaJ, aged 8 to 12 weeks) were anesthetized and subjected to survival surgery to expose the bulla of the right ear. A ouabain solution (3 mM, approximately 10 ul) was administered in the round window niche. This solution was wicked away and replaced with fresh ouabain approximately every 10 min during a cummulative exposure period of 60 min. The left ears (i.e., contralateral) were not surgically manipulated and were used as controls. Mice were maintained for 3 days or 7 days following treatments, then euthanized, and the oubain-treated and contralateral cochleas were removed. Cochleas underwent microdissection to remove the outer bony cochlear shell and cochlear lateral wall, thus preserving the modiolus portion of cochlea which contains mainly the auditory nerve. All sample types were prepared in experimental triplicate (n=3).
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Project description:This study demonstrates the baseline data of gradient gene expression in the cochlea. Especially for genes whose mutations cause autosomal dominant non syndromic hearing loss (Pou4f3, Slc17a8, Tmc1, and Crym) as well as genes important for cochlear function (Emilin-2 and Tectb), gradual expression changes help to explain the various pathological conditions. Four C57BL/6 mice aged 6 weeks cochlea samples including the lateral wall, stria vascularis, spiral ligament, spiral prominence, and the organ of corti were dissected and separated into the apical, middle and basal turns to compare gene expression profiles of each cochlea turn.
2014-01-08 | E-GEOD-53863 | biostudies-arrayexpress
Project description:A rat model of acute mitochondrial dysfunction in the cochlea is created by applying an irreversible mitochondrial complex II enzyme inhibitor, 3-NP, directly to the round window membrane. Treatment with 300 mM 3-NP results in temporary hearing loss (temporary threshold shift (TTS) model), whereas treatment with 500 mM 3-NP results in profound and permanent hearing loss (permanent threshold shift (PTS) model. Either treatment results with a primary histological change in the lateral wall spiral ligament. Because local ATP deprivation in the inner ear results from inhibition of inner ear mitochondrial function, this model replicates the etiology of inner ear energy failure caused by ATP deprivation due to inner ear ischemia. We used microarrays to detail the global programme of gene expression in the damaged cochlear lateral wall by 3NP and identified distinct classes of up-regulated/ down-regulated genes during the process. One and three day after administrated either 300 mM of 3-NP (TTS-1d and TTS-3d, respectably) or saline (Ctrl-1d and Ctrl-3d, respectably), rat cochear lateral wall in the apical side of the basal turn was harvested for RNA extraction and hybridization on Affymetrix microarrays.
2013-11-20 | E-GEOD-52500 | biostudies-arrayexpress
Project description:We have employed a novel approach for the identification of functionally important microRNA (miRNA)-target interactions using integrated miRNA, transcriptome and proteome profiles with advanced in silico analysis. By looking at both the transcript and protein levels of expression, a thorough coverage of miRNA regulation was obtained. Microdissected auditory and vestibular sensory epithelia were used as the model system, thus being the first time such a comparison was carried out in a neuroepithelial system. Moreover, this is one of only a few studies employing proteome screening for the identification of miRNA targets. Notably, this approach can be employed for the study of other tissues and organs. We detected the expression of 157 miRNAs in the inner ear sensory epithelia, with 53 miRNAs differentially expressed between the cochlea and vestibule. By searching for enrichment and depletion of miRNA targets in the transcript and protein datasets with a reciprocal or similar expression, respectively, as the regulatory miRNA, we identified functionally important miRNAs. Finally, the interaction between miR-135b and PSIP1-P75, a transcriptional coacitvator previously unknown in the inner ear, was identified and validated experimentally. We suggest that miR-135b may serve as a cellular effector, involved in regulating some of the differences between the cochlear and vestibular hair cells. We investigated the mRNA expression profile of the cochlear and vestibular sensory epithelia from inner ears of postnatal day 2 mice using the Affymetrix GeneChip® 430 2Mouse Genome array. Cochlear and vestibular sensory epithelia were dissected from wild type C3H mice and collected separately. The vestibular epithelia consisted of the saccule, utricle and the lateral and anterior cristae. Both the cochlear and vestibular sensory epithelia were dissected with their underlying mesenchyma. Altogether three pools, three biological replicates, of each tissue type were collected consisting of cochlear or vestibular sensory epithelia dissected from 10 to 12 inner ears.
2011-04-20 | E-GEOD-23081 | biostudies-arrayexpress
Project description:Our work describes the application of mass spectrometry-based label-free quantitative proteomics for the identification of differentially expressed proteins between different-aged cochlea. We report proteins exclusively present as well as up- and downregulated in the cochlear sensory epithelium at significant developmental stages. Additionally, we report proteins exclusively present on P3 that were recently identified in the cochlea for the first time. We use bioinformatics to provide insight on biological functions and potential primary and secondary partners of the differentially expressed proteins. This study provides the first differentially expressed proteome in the mammalian cochlea at significant developmental stages; before hearing, during the onset of hearing, and when hearing is fully developed. We believe that these results will provide insights into the function of proteins that change during development and identify potential protein biomarkers related to hearing impairments.
2018-08-29 | PXD001973 | Pride
Project description:Glucocorticoid responsive AIED patients demonstrate alternate splicing of IL1R2 in response to dexamethasone prior to treatment. Identification of IL1R2 as a potential target gene in AIED was determined by a microarray analysis of patients with end-stage AIED and controls with non-immunologic etiologies of hearing loss undergoing cochlear implantation. Experiment Overall Design: Patients with either end-stage AIED or controls with non-immunologic etiologies of hearing loss undergoing cochlear implantation were enrolled. All patients received pneumovax 2 weeks prior to surgery. At the time of surgery, blood was taken for PBMC isolation and autologous perilymph was harvested from a bloodless field. For each patient, 3 microarrays were performed: (1) unstimulated PBMC, (2) pneumovax stimulated PBMC, (3) autologous perilymph stimulated PBMC. All conditions were compared for the AIED and control subjects. IL1R2 was identified as induced in controls, but not AIED patients, in response to autologous perilymph. Findings were confirmed by QPCR.
2009-05-11 | E-GEOD-4277 | biostudies-arrayexpress
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