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MicroRNAs as Regulators of Aging Processes in the Cochlear Lateral Wall of the Mouse Inner Ear (mRNA data set)

ABSTRACT: Age-related hearing loss (presbycusis) affects more than one-third of Americans over the age of 60, with its prevalence and severity increasing with age. Pathological alterations to the cochlear lateral wall (CLW) disrupting the maintenance of the endocochlear potential (EP) are a major cause of (metabolic) presbycusis. Although molecular mediators of CLW degeneration are largely unknown, several cellular events, including oxidative stress, apoptosis, and inhibition of proliferation, are known to contribute to this dysfunction. Here we have analyzed mRNA and microRNA expression in CLW of young and old mice to profile transcriptional changes that occur as a function of aging. Our results reinforce prior findings about molecular processes and pathways affected by aging and implicate microRNAs that may be involved in influencing these changes.

ORGANISM(S): Mus musculus

PROVIDER: GSE98070 | GEO | 2021/04/14

REPOSITORIES: GEO

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MicroRNAs as Regulators of Aging Processes in the Cochlear Lateral Wall of the Mouse Inner Ear (microRNA data set)

Project description:Age-related hearing loss (presbycusis) affects more than one-third of Americans over the age of 60, with its prevalence and severity increasing with age. Pathological alterations to the cochlear lateral wall (CLW) disrupting the maintenance of the endocochlear potential (EP) are a major cause of (metabolic) presbycusis. Although molecular mediators of CLW degeneration are largely unknown, several cellular events, including oxidative stress, apoptosis, and inhibition of proliferation, are known to contribute to this dysfunction. Here we have analyzed mRNA and microRNA expression in CLW of young and old mice to profile transcriptional changes that occur as a function of aging. Our results reinforce prior findings about molecular processes and pathways affected by aging and implicate microRNAs that may be involved in influencing these changes.

2021-04-14 | GSE98071 | GEO

MicroRNAs Involved in Aging of the Lateral Wall of the Cochlear Duct

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 The totoal RNA was extracted from the lateral wall of cochlear duct from CBA/J and C57BL/6J mice at different ages. The expression profile of miRNAs was examined by miR microarray GeneChip.

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Caloric restriction suppresses apoptotic cell death in the mammalian cochlea and leads to prevention of presbycusis

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Transcription profiling of mouse with unilateral cochlear removal in Cochlear Nucleus at P7 and P21

Project description:Deprivation of peripheral nerve input by cochlear removal in young mice results in dramatic neuron death in the cochlear nucleus (CN). The same manipulation in older mice does not result in significant loss. The molecular basis of this critical period of vulnerability remains largely unknown. Here we identified genes regulated at early time points after cochlear removal at ages when neurons are vulnerable (postnatal day (P)7) or invulnerable (P21) to this challenge. Afferent deprivation regulated very different sets of genes at P7 and P21. These genes showed a variety of functions at both ages, but surprisingly there was no net increase in pro-apoptotic genes at P7. A large set of upregulated immune-related genes was identified at P21. Experiment Overall Design: Mice received unilateral cochlear removals. At 6, 12, 24, and 48 hours after surgery, the CN ipsilateral and contralateral were removed, and RNA isolated from separate pools of tissue for each replicate. Deafferented CN were compared to age-matched and time-matched contralateral, control CN to identify genes regulated by cochlear removal at age P7 and P21.

2008-06-13 | E-GEOD-5394 | biostudies-arrayexpress

Transcription profiling of cochleae from young and middle aged mice subjected to calorie restriction to examine age-related changes and calorie restriction-induced changes in gene expression in the cochlea.

Project description:Presbycusis is characterized by an age-related progressive decline of auditory function, and arises mainly from the degeneration of hair cells or spiral ganglion (SG) cells in the cochlea. Here we show that caloric restriction suppresses apoptotic cell death in the mouse cochlea and prevents late onset of presbycusis. Caloric restricted mice, which maintained body weight at the same level as that of young control (YC) mice, retained normal hearing and showed no cochlear degeneration. CR mice also showed significantly fewer TUNEL-positive staining cells and fewer cleaved caspase-3-positive staining cells relative to middle-age control (MC) mice. Microarray analysis revealed that CR down-regulated the expression of 28 proapoptotic genes, including Bak and Bim. Taken together, our findings suggest that loss of critical cells through apoptosis is an important mechanism of presbycusis in mammals, and that CR or staying lean can retard this process by suppressing apoptosis in the inner ear tissue. Experiment Overall Design: To examine the effects of aging, a comparison of cochlea tissues from YC (3 samples) and MC (3 samples) mice was conducted. To examine the effects of calorie restriction (CR), a comparison of cochleae from MC (3 samples) and CR (3 samples) mice was conducted. We examined age-related changes in gene expression in the cochlea and calorie restriction-induced changes in gene expression in the cochlea. We pooled four cochleae from two mice for one sample and used three samples per group (n = 3). Quality control measures were not used. No replicates were done. Dye swap was not used.

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Project description:Presbycusis – age-related hearing loss – is the number one communicative disorder of our aged population. Here we analyzed gene expression for a set of GABA receptors in the cochlea of aging CBA mice using the Affymetrix GeneChip MOE430A. Functional phenotypic hearing measures distortion-product otoacoustic emission (DPOAE) amplitudes (four age groups) were made. The gene expression changes from RMA normalized microarray data (40 replicates) were first subjected to one-way ANOVA, and then linear regression was performed. In addition, the log signal ratio was converted to fold change, and selected gene expression changes were confirmed by relative real-time PCR. Major findings: expression of GABA-A receptor subunit 6was upregulated with age and hearing loss, whereas subunit 1 was repressed. In addition, GABA-A receptor associated protein like-1 and GABA-A receptor associated protein like-2 were strongly downregulated with age and hearing impairment. Lastly, gene expression measures were correlated with pathway/network relationships relevant to the inner ear using Pathway Architect, to identify key pathways consistent with the gene expression changes observed. In the study of expression changes GABA receptors in the in cochlea of young adult and aging presbycusis mice total of forty chips were used. The normal aging mice were in four groups young adults controls with good hearing (8 mice, 8 MOE430A GeneChips), Middle aged group with good hearing ( 17 mice, 17 MOE430A GeneChips), Mild Presbycusis (old) with limited hearing loss (9 mice, 9 MOE430A GeneChips) and Severe Presbycusis (old) (6 mice, 6 MOE430A GeneChips). Each Mice cochlea to each GeneChips, Samples was not pooled. The hearing potential evidence of each mouse is accompanied with each mice DPOAE amplitude.

2013-08-06 | E-GEOD-49543 | biostudies-arrayexpress

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