Expression Profiling of MicroRNAs in the Inner Ear of Elderly People by Real-Time PCR Quantification

2017 ◽  
Vol 22 (3) ◽  
pp. 135-145 ◽  
Author(s):  
Kuwon Sekine ◽  
Tomohiro Matsumura ◽  
Toshihiro Takizawa ◽  
Yurika Kimura ◽  
Shiho Saito ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Inner Ear ◽  
Real Time Pcr ◽  
Expression Profiling ◽  
Molecular Mechanisms ◽  
Elderly Subjects ◽  
Age Related ◽  
Inner Ear Development ◽  
Temporal Bones ◽  
Age Related Hearing Loss

The molecular mechanisms underlying age-related hearing loss are unknown, and currently, there is no treatment for this condition. Recent studies have shown that microRNAs (miRNAs) and age-related diseases are intimately linked, suggesting that some miRNAs may present attractive therapeutic targets. In this study, we obtained 8 human temporal bones from 8 elderly subjects at brain autopsy in order to investigate the expression profile of miRNAs in the inner ear with miRNA arrays. A mean of 478 different miRNAs were expressed in the samples, of which 348 were commonly expressed in all 8 samples. Of these, levels of 16 miRNAs significantly differed between young elderly and old elderly subjects. miRNAs, which play important roles in inner ear development, were detected in all samples, i.e., in both young and old elderly subjects, whether with or without hearing loss. Our results suggest that these miRNAs play important roles not only in development, but also in the maintenance of inner ear homeostasis.

Molecular mechanisms of age-related hearing loss

2002 ◽  
Vol 1 (3) ◽  
pp. 331-343 ◽  
Author(s):  
Michael D. Seidman ◽  
Nadir Ahmad ◽  
Uma Bai
Keyword(s):  
Hearing Loss ◽  
Molecular Mechanisms ◽  
Age Related ◽  
Age Related Hearing Loss

scholarly journals Prediction of the Molecular Mechanisms Underlying Erlong Zuoci Treatment of Age-Related Hearing Loss via Network Pharmacology-Based Analyses Combined with Experimental Validation

2021 ◽  
Vol 12 ◽  
Author(s):  
Qing Liu ◽  
Ning Li ◽  
Yifang Yang ◽  
Xirui Yan ◽  
Yang Dong ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Experimental Validation ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Synaptic Connections ◽  
Target Proteins ◽  
Age Related ◽  
Age Related Hearing Loss

Background: The traditional Chinese medicine formula ErLong ZuoCi (ELZC) has been extensively used to treat age-related hearing loss (ARHL) in clinical practice in China for centuries. However, the underlying molecular mechanisms are still poorly understood.Objective: Combine network pharmacology with experimental validation to explore the potential molecular mechanisms underlying ELZC with a systematic viewpoint.Methods: The chemical components of ELZC were collected from the Traditional Chinese Medicine System Pharmacology database, and their possible target proteins were predicted using the SwissTargetPrediction database. The putative ARHL-related target proteins were identified from the database: GeneCards and OMIM. We constructed the drug-target network as well as drug-disease specific protein-protein interaction networks and performed clustering and topological property analyses. Functional annotation and signaling pathways were performed by gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. Finally, in vitro experiments were also performed to validate ELZC’s key target proteins and treatment effects on ARHL.Results: In total, 63 chemical compounds from ELZC and 365 putative ARHL-related targets were identified, and 1860 ARHL-related targets were collected from the OMIM and GeneCards. A total of 145 shared targets of ELZC and ARHL were acquired by Venn diagram analysis. Functional enrichment analysis suggested that ELZC might exert its pharmacological effects in multiple biological processes, such as cell proliferation, apoptosis, inflammatory response, and synaptic connections, and the potential targets might be associated with AKT, ERK, and STAT3, as well as other proteins. In vitro experiments revealed that ELZC pretreatment could decrease senescence-associated β-galactosidase activity in hydrogen peroxide-induced auditory hair cells, eliminate DNA damage, and reduce cellular senescence protein p21 and p53. Finally, Western blot analysis confirmed that ELZC could upregulate the predicted target ERK phosphorylation.Conclusion: We provide an integrative network pharmacology approach, in combination with in vitro experiments to explore the underlying molecular mechanisms governing ELZC treatment of ARHL. The protective effects of ELZC against ARHL were predicted to be associated with cellular senescence, inflammatory response, and synaptic connections which might be linked to various pathways such as JNK/STAT3 and ERK cascade signaling pathways. As a prosperous possibility, our experimental data suggest phosphorylation ERK is essential for ELZC to prevent degeneration of cochlear.

scholarly journals Role of Oxidative Stress in the Senescence Pattern of Auditory Cells in Age-Related Hearing Loss

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1497
Author(s):  
Luz del Mar Rivas-Chacón ◽  
Sofía Martínez-Rodríguez ◽  
Raquel Madrid-García ◽  
Joaquín Yanes-Díaz ◽  
Juan Ignacio Riestra-Ayora ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
Molecular Mechanisms ◽  
Morphological Changes ◽  
Cell Damage ◽  
Stria Vascularis ◽  
Organ Of Corti ◽  
Age Related ◽  
Age Related Hearing Loss

Age-related hearing loss (ARHL) is an increasing and gradual sensorineural hearing dysfunction. Oxidative stress is an essential factor in developing ARHL; additionally, premature senescence of auditory cells induced by oxidative stress can produce hearing loss. Hydrogen peroxide (H2O2) represents a method commonly used to generate cellular senescence in vitro. The objective of the present paper is to study H2O2-induced senescence patterns in three auditory cell lines (House Ear Institute-Organ of Corti 1, HEI-OC1; organ of Corti, OC-k3, and stria vascularis, SV-k1 cells) to elucidate the intrinsic mechanisms responsible for ARHL. The auditory cells were exposed to H2O2 at different concentrations and times. The results obtained show different responses of the hearing cells concerning cell growth, β-galactosidase activity, morphological changes, mitochondrial activation, levels of oxidative stress, and other markers of cell damage (Forkhead box O3a, FoxO3a, and 8-oxoguanine, 8-oxoG). Comparison between the responses of these auditory cells to H2O2 is a helpful method to evaluate the molecular mechanisms responsible for these auditory cells’ senescence. Furthermore, this in vitro model could help develop anti-senescent therapeutic strategies for the treatment of AHRL.

The miR-34a/Bcl-2 Pathway Contributes to Auditory Cortex Neuron Apoptosis in Age-Related Hearing Loss

2017 ◽  
Vol 22 (2) ◽  
pp. 96-103 ◽  
Author(s):  
Qiuhong Huang ◽  
Yongkang Ou ◽  
Hao Xiong ◽  
Haidi Yang ◽  
Zhigang Zhang ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Auditory Cortex ◽  
Molecular Mechanisms ◽  
Primary Auditory Cortex ◽  
Auditory Brainstem ◽  
Hearing Ability ◽  
Age Related ◽  
Brainstem Response ◽  
The Central Nervous System ◽  
Age Related Hearing Loss

Hypothesis: The miR-34a/Bcl-2 signaling pathway may play a role in the mechanisms related to age-related hearing loss (AHL) in the auditory cortex. Background: The auditory cortex plays a key role in the recognition and processing of complex sound. It is difficult to explain why patients with AHL have poor speech recognition, so increasing numbers of studies have focused on its central change. Although micro (mi)RNAs in the central nervous system have recently been increasingly reported to be associated with age-related diseases, the molecular mechanisms of AHL in the auditory cortex are not fully understood. Methods: The auditory brainstem response was used to assess the hearing ability of C57BL/6 mice, and q-PCR, immunohistochemistry, and Western blotting were used to detect the expression levels of miR-34a and Bcl-2 in the mouse auditory cortex. TUNEL and DNA fragmentation were adopted to detect the apoptosis of neurons in the auditory cortex. To verify the relationship of miR-34a and Bcl-2, we transfected an miR-34a mimic or miR-34a inhibitor into primary auditory cortex neurons. Results: In this study, miR-34a/Bcl-2 signaling was examined in auditory cortex neurons during aging. miR-34a and apoptosis increased in the auditory cortex neurons of C57BL/6 mice with aging, whereas an age-related decrease in Bcl-2 was determined. In the primary neurons of the auditory cortex, miR-34a overexpression inhibited Bcl-2, leading to an increase in apoptosis. Moreover, miR-34a knockdown increased Bcl-2 expression and diminished apoptosis. Conclusion: Our results support a link between age-related apoptosis in auditory cortex neurons and miR-34a/Bcl-2 signaling, which may serve as a potential mechanism of the expression of AHL in the auditory cortex.

scholarly journals Transcriptomic analysis highlights cochlear inflammation associated with age-related hearing loss in C57BL/6 mice using next generation sequencing

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9737
Author(s):  
Zhongwu Su ◽  
Hao Xiong ◽  
Yi Liu ◽  
Jiaqi Pang ◽  
Hanqing Lin ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Next Generation Sequencing ◽  
Molecular Mechanisms ◽  
Transcriptomic Analysis ◽  
Differentially Expressed ◽  
Next Generation ◽  
Age Related ◽  
Cochlear Inflammation ◽  
Age Related Hearing Loss ◽  
Generation Sequencing

Background In our aging society, age-related hearing loss (AHL) is the most common sensory disorder in old people. Much progress has been made in understanding the pathological process of AHL over the past few decades. However, the mechanism of cochlear degeneration during aging is still not fully understood. Methods Next generation sequencing technique was used to sequence the whole transcriptome of the cochlea of C57BL/6 mice, a mouse model of AHL. Differentially expressed genes (DEGs) were identified using the Cuffdiff software. GO and KEGG pathway enrichment analyses of the DEGs were implemented by using the GOseq R package and KOBAS software, respectively. Results A total of 731 genes (379 up- and 352 down-regulated) were revealed to be differentially expressed in the cochlea of aged mice compared to the young. Many genes associated with aging, apoptosis, necroptosis and particularly, inflammation were identified as being significantly modulated in the aged cochlea. GO and KEGG analyses of the upregulated DEGs revealed that the most enriched terms were associated with immune responses and inflammatory pathways, whereas many of the downregulated genes are involved in ion channel function and neuronal signaling. Real-time qPCR showed that H2O2 treatment significantly induced the expression of multiple inflammation and necroptosis-related genes in HEI-OC1 cells. Conclusion Using next generation sequencing, our transcriptomic analysis revealed the differences of gene expression pattern with age in the cochlea of C57BL/6 mice. Our study also revealed multiple immune and inflammatory transcriptomic changes during cochlear aging and provides new insights into the molecular mechanisms underlying cochlear inflammation in AHL.

scholarly journals Age-Related Hearing Loss Is Dominated by Damage to Inner Ear Sensory Cells, Not the Cellular Battery That Powers Them

2020 ◽  
Vol 40 (33) ◽  
pp. 6357-6366 ◽  
Author(s):  
Pei-zhe Wu ◽  
Jennifer T. O'Malley ◽  
Victor de Gruttola ◽  
M. Charles Liberman
Keyword(s):  
Hearing Loss ◽  
Inner Ear ◽  
Sensory Cells ◽  
Age Related ◽  
Age Related Hearing Loss

scholarly journals Hippocampal Transcriptome-Wide Association Study Reveals Correlations Between Impaired Glutamatergic Synapse Pathway and Age-Related Hearing Loss in BXD-Recombinant Inbred Mice

2021 ◽  
Vol 15 ◽  
Author(s):  
Tingzhi Deng ◽  
Jingjing Li ◽  
Jian Liu ◽  
Fuyi Xu ◽  
Xiaoya Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hearing Loss ◽  
Association Study ◽  
Learning And Memory ◽  
Cognitive Dysfunction ◽  
Molecular Mechanisms ◽  
Gene Expression Pattern ◽  
Glutamatergic Synapse ◽  
Age Related ◽  
Age Related Hearing Loss

Age-related hearing loss (ARHL) is associated with cognitive dysfunction; however, the detailed underlying mechanisms remain unclear. The aim of this study is to investigate the potential underlying mechanism with a system genetics approach. A transcriptome-wide association study was performed on aged (12–32 months old) BXD mice strains. The hippocampus gene expression was obtained from 56 BXD strains, and the hearing acuity was assessed from 54 BXD strains. Further correlation analysis identified a total of 1,435 hearing-related genes in the hippocampus (p < 0.05). Pathway analysis of these genes indicated that the impaired glutamatergic synapse pathway is involved in ARHL (p = 0.0038). Further gene co-expression analysis showed that the expression level of glutamine synthetase (Gls), which is significantly correlated with ARHL (n = 26, r = −0.46, p = 0.0193), is a crucial regulator in glutamatergic synapse pathway and associated with learning and memory behavior. In this study, we present the first systematic evaluation of hippocampus gene expression pattern associated with ARHL, learning, and memory behavior. Our results provide novel potential molecular mechanisms involved in ARHL and cognitive dysfunction association.

scholarly journals Comparison of Age-Related Pigmentary Changes in the Auditory and Vestibular Systems Within Mouse and Human Temporal Bones

2021 ◽  
Vol 15 ◽  
Author(s):  
Nicholas S. Andresen ◽  
Sarah Coreas ◽  
Dillan F. Villavisanis ◽  
Amanda M. Lauer
Keyword(s):  
Hearing Loss ◽  
African American ◽  
Temporal Bone ◽  
Vestibular System ◽  
Stria Vascularis ◽  
Vestibular Dysfunction ◽  
Melanin Pigmentation ◽  
Age Related ◽  
Temporal Bones ◽  
Age Related Hearing Loss

BackgroundMelanin pigmentation is present within the auditory and vestibular systems of the mammalian inner ear and may play a role in maintaining auditory and vestibular function. Melanocytes within the stria vascularis (SV) are necessary for the generation of the endocochlear potential (EP) and decreased EP has been linked to age-related hearing loss. Melanocytes and pigment-containing “dark cells” are present within the vestibular system, but have a less well-defined role. African–American individuals have increased pigmentation within the SV and vestibular system, which is hypothesized to be related to lower rates of age-related hearing loss and vestibular dysfunction. It remains unclear if increased pigmentation confers lifelong protection against hearing loss and vestibular dysfunction.MethodsMouse temporal bones were collected from juvenile (3–4 week) and aged (20–32 months) CBA/CaJ mice. Pediatric and adult human temporal bones from Caucasian or African–American individuals were examined from the Johns Hopkins Temporal Bone Collection. Information regarding Fitzpatrick skin type were unavailable, and self-identified race/ethnicity was used as a proxy. Images were taken using light microscopy at 20× magnification. ImageJ software (v1.53) was used to measure pigment within the SV and vestibular system.ResultsIn mouse temporal bones pigmentation within the SV increased with age, but pigmentation within the vestibular system did not increase with age. In human temporal bones pigmentation within the SV increased with age and pigmentation within the vestibular system increased within the wall of the utricle, but not other regions of the vestibular system. African–American individuals had higher amounts of pigment within the SV and vestibular system, among both pediatric and adult populations.ConclusionStria vascularis pigmentation increases with age in mouse and human temporal bones. Pigmentation within the vestibular system did not increase with age in mouse specimens and only increased within the utricular wall with age in human specimens. Individuals who identified as African–American had higher pigment content within the SV and vestibular system, both as children and as adults. These results highlight how similar age-related pigmentary changes occur in the auditory and vestibular systems across species and underscore the importance of racial/ethnic diversity in human temporal bone studies.

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