Age-related changes in gene expression in mouse cochlea
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE121856 | GEO | 2020/10/31
REPOSITORIES: GEO
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Project description:Age-related hearing loss (AHL) is the progressive loss of auditory function with aging. The DBA/2J (DBA) mice have been used as a model of AHL and undergoes progressive, age-related hearing loss by 12 weeks of age. Here we analyzed cochlear gene expression of 7-week-old and 36-week-old DBA mice using microarrays. Auditory brainstem response (ABR) analysis confrimed that severe age-related hearing loss occured in 36-week-old mice, whereas moderate hearing loss occured in 7-week-old mice. Comprehensive gene expression analysis identified genes correlated with AHL and revealeed that 15 mitochondrial process categories, including â??mitochondrial electron transport chainâ??, â??oxidative phosphorylationâ??, â??respiratory chain complex Iâ??, â??respiratory chain complex IVâ??, and â??respiratory chain complex Vâ??, were statistically associated with AHL-correlated genes in the cochlea of 36-week-old DBA mice, and that 25 genes encoding components of the mitochondrial respiratory chain (respiratory chain complex I, IV, and V) were significantly down-regulated in the cochlea. These observations provide evidence that AHL is associated with down-regulation of genes involved in the mitochondrial respiratory chain in the cochlea of DBA mice, and suggest that mitochondrial respiratory chain dysfunction may be a key feature of AHL in mammalian cochlea. Experiment Overall Design: To determine the effects of age-related hearing loss, each 7-week-old sample (n = 3) was compared to each 36-week-old sample (n = 3), generating a total of nine pairwise comparisons. Using DAVIS and EASE, the identified genes were assign to â??GO: Biological Processâ?? categories of Gene Ontology Consortium. Furthermore, we used EASE to determine the total number of genes that were assigned to each biological process category, and to perform Fisher exact test. Quality control measures were not used. No replicates were done. Dye swap was not used.
2008-06-14 | E-GEOD-6045 | biostudies-arrayexpress
Project description:To show that FST cooperates with SHH to establish tonotopy by promoting apical cochlear characteristics responsible for low-frequency hearing in mammals, we analyzed cochlear gene expression, morphology, and auditory function of mouse mutants with loss or gain of SHH function in combination with loss or gain of follistatin (FST) function.
2022-12-17 | GSE203228 | GEO
Project description:Various organ failure induced by chronic intake of GeO2 is one of the well known disease related to mitochondrial dysfunction. The 0.15% GeO2 treated CBA mice shows severe hearing loss in 4M. Here we analyzed cochlear gene expression of 6 months old CBA mice using microarrays treated with normal chow or that containing 0.15% GeO2 for four months. Auditory brainstem response (ABR) analysis confirmed that severe age-related hearing loss occured in GeO2 treated mice, whereas no hearing loss occured in normal chow treated mice. Comprehensive gene expression analysis identified genes correlated with GeO2-induced mithochodrial dysfunction genes and revealed that 28 genes encoding components of the mitochondrial respiratory chain were significantly down-regulated. These observations provide evidence that GeO2-induced hearing loss is associated with the down-regulation of genes involved in the mitochondrial respiratory chain complexes in the cochlea of CBA mice. To determine the effects of GeO2, each control sample (n=5) was compared to each GeO2-intoxicated (n=5), generating a total of 25 pairwise comparisons. Using DAVIS and EASE, the identified genes were assign to GO: Biological Process categories of Gene Ontology Consortium. Furthermore, we used EASE to determine the total number of genes that were assigned to each biological process category, and to perform Fisher exact test. Quality control measures were not used. No replicates were done. Dye swap was not used.
2016-07-22 | E-GEOD-84735 | biostudies-arrayexpress
Project description:Age-related hearing loss (AHL) is the progressive loss of auditory function with aging. The DBA/2J (DBA) mice have been used as a model of AHL and undergoes progressive, age-related hearing loss by 12 weeks of age. Here we analyzed cochlear gene expression of 7-week-old and 36-week-old DBA mice using microarrays. Auditory brainstem response (ABR) analysis confrimed that severe age-related hearing loss occured in 36-week-old mice, whereas moderate hearing loss occured in 7-week-old mice. Comprehensive gene expression analysis identified genes correlated with AHL and revealeed that 15 mitochondrial process categories, including “mitochondrial electron transport chain”, “oxidative phosphorylation”, “respiratory chain complex I”, “respiratory chain complex IV”, and “respiratory chain complex V”, were statistically associated with AHL-correlated genes in the cochlea of 36-week-old DBA mice, and that 25 genes encoding components of the mitochondrial respiratory chain (respiratory chain complex I, IV, and V) were significantly down-regulated in the cochlea. These observations provide evidence that AHL is associated with down-regulation of genes involved in the mitochondrial respiratory chain in the cochlea of DBA mice, and suggest that mitochondrial respiratory chain dysfunction may be a key feature of AHL in mammalian cochlea. Keywords: Disease state analysis, Time course analysis
2007-10-16 | GSE6045 | GEO
Project description:Various organ failure induced by chronic intake of GeO2 is one of the well known disease related to mitochondrial dysfunction. The 0.15% GeO2 treated CBA mice shows severe hearing loss in 4M. Here we analyzed cochlear gene expression of 6 months old CBA mice using microarrays treated with normal chow or that containing 0.15% GeO2 for four months. Auditory brainstem response (ABR) analysis confirmed that severe age-related hearing loss occured in GeO2 treated mice, whereas no hearing loss occured in normal chow treated mice. Comprehensive gene expression analysis identified genes correlated with GeO2-induced mithochodrial dysfunction genes and revealed that 28 genes encoding components of the mitochondrial respiratory chain were significantly down-regulated. These observations provide evidence that GeO2-induced hearing loss is associated with the down-regulation of genes involved in the mitochondrial respiratory chain complexes in the cochlea of CBA mice.
2016-07-22 | GSE84735 | GEO
Project description:Age-related hearing impairment (ARHI), one of the most common medical conditions, is strongly heritable, yet its genetic causes remain largely unknown. We conducted a meta-analysis of GWAS summary statistics from multiple hearing-related traits in the UK Biobank (n = up to 323,978) and identified 31 genome-wide significant risk loci for self-reported hearing difficulty (p < 5e-8), of which 30 have not been reported previously at genome-wide significance. We interpreted these loci in the context of newly generated ATAC-seq and single-cell RNA-seq from cells in the mouse cochlea. Risk-associated genes were enriched for expression in cochlear epithelial and non-epithelial cells, as well as for genes related to sensory perception and known Mendelian deafness genes, supporting their relevance to auditory function. Regions of the human genome homologous to open chromatin in sensory epithelial cells from the mouse were strongly enriched for heritable risk for hearing difficulty, even after adjusting for baseline effects of evolutionary conservation and cell-type non-specific regulatory regions. Epigenomic and statistical fine-mapping most strongly supported 50 putative risk genes. Of these, at least 45 were expressed in mouse cochlea and 15 were enriched specifically in sensory hair cells. These results reveal new risk loci and risk genes for hearing difficulty and suggest an important role for altered gene regulation in the cochlear sensory epithelium.
2020-08-01 | GSE135737 | GEO
Project description:Age-related hearing (ARHL) loss affects a large part of the human population with a major impact on our aging societies. Yet, underlying mechanisms are not understood, and no validated therapy or prevention exists. NADPH oxidases (NOX), are important sources of reactive oxygen species (ROS) in the cochlea and might therefore be involved in the pathogenesis of ARHL. Here we investigate ARHL in a mouse model. Wild type mice showed early loss of hearing and cochlear integrity, while animals deficient in the NOX subunit p22phox remained unaffected up to six months. Genes of the excitatory pathway were down-regulated in p22phox-deficient auditory neurons. Our results demonstrate that NOX activity leads to upregulation of genes of the excitatory pathway, to excitotoxic cochlear damage, and ultimately to ARHL. In the absence of functional NOXs, aging mice conserve hearing and cochlear morphology. Our study offers new insights into pathomechanisms and future therapeutic targets of ARHL.
2020-12-18 | E-MTAB-8668 | biostudies-arrayexpress
Project description:The genetic bases underlying the evolution of morphological and functional innovations of the mammalian inner ear are poorly understood. Gene regulatory regions are thought to play an important role in the evolution of form and function. To uncover crucial hearing genes whose regulatory machinery evolved specifically in mammalian lineages, we mapped accelerated noncoding sequences (ACNEs) in inner ear transcription factors (TFs) identifying PKNOX2 as the gene displaying the largest amount of ACNEs. To investigate the function of PKNOX2-ACNEs, we tested them using enhancer assays in transgenic zebrafish and unmasked transcriptional enhancers that acquired novel expression patterns as a consequence of the evolutionary process they underwent. Even though PKNOX2 is one of the most highly expressed genes in cochlear hair cells, its function was unknown. Thus, to explore the role of PKNOX2 in mammalian hearing, we generated Pknox2 null mice using CRISPR/Cas9 technology. Pknox2-/- mice exhibited reduced distortion product otoacoustic emissions (DPOAEs) and auditory brainstem response (ABR) thresholds at high frequencies together with an increase in peak 1 amplitude, consistent with a higher number of IHCs-auditory nerve synapsis observed at the cochlear basal region. A comprehensive cochlear transcriptomic analysis of Pknox2-/- and Pknox2+/+ mice revealed that key auditory genes are under Pknox2 control. Hence, we report, for the first time, that PKNOX2 has a critical function regulating cochlear sensitivity at higher frequencies and that its regulatory machinery underwent lineage-specific evolution, providing novel insight into the contribution of this TF to normal auditory function and to the evolution of high-frequency hearing.
2023-06-01 | GSE171921 | GEO
Project description:Hearing mediates many behaviors critical for survival in echolocating bats, including foraging and navigation. Although most mammals are susceptible to progressive age-related hearing loss, the evolution of biosonar, which requires the ability to hear low-intensity echoes from outgoing sonar signals, may have selected against the development of hearing deficits in bats. Many echolocating bats exhibit exceptional longevity and rely on acoustic behaviors for survival to old age; however relatively little is known about the aging bat auditory system. In this study, we used DNA methylation to estimate the ages of wild-caught big brown bats (Eptesicus fuscus) and measured hearing sensitivity in young and aging bats using auditory brainstem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs). We found no evidence for hearing deficits in bats up to 12.5 years of age, demonstrated by comparable thresholds and similar ABR and DPOAE amplitudes across age groups. We additionally found no significant histological evidence for cochlear aging, with similar hair cell counts, afferent, and efferent innervation patterns in young and aging bats. Here we demonstrate that big brown bats show minimal evidence for age-related hearing loss and therefore represent informative models for investigating mechanisms that may preserve hearing function over a long lifetime.
2024-09-30 | GSE274777 | 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. 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