Functional, Morphological and Molecular Changes Reveal the Mechanisms Associated with Age-Related Vestibular Loss
Age-related loss of vestibular function and hearing are common disorders that arise from the loss of function of the inner ear and significantly decrease quality of life. The underlying pathophysiological mechanisms are poorly understood and difficult to investigate in humans. Therefore, our study e...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-09-01
|
| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/13/9/1429 |
| _version_ | 1827726939200159744 |
|---|---|
| author | Vasiliki Georgia Paplou Nick M. A. Schubert Marcel van Tuinen Sarath Vijayakumar Sonja J. Pyott |
| author_facet | Vasiliki Georgia Paplou Nick M. A. Schubert Marcel van Tuinen Sarath Vijayakumar Sonja J. Pyott |
| author_sort | Vasiliki Georgia Paplou |
| collection | DOAJ |
| description | Age-related loss of vestibular function and hearing are common disorders that arise from the loss of function of the inner ear and significantly decrease quality of life. The underlying pathophysiological mechanisms are poorly understood and difficult to investigate in humans. Therefore, our study examined young (1.5-month-old) and old (24-month-old) C57BL/6 mice, utilizing physiological, histological, and transcriptomic methods. Vestibular sensory-evoked potentials revealed that older mice had reduced wave I amplitudes and delayed wave I latencies, indicating reduced vestibular function. Immunofluorescence and image analysis revealed that older mice exhibited a significant decline in type I sensory hair cell density, particularly in hair cells connected to dimorphic vestibular afferents. An analysis of gene expression in the isolated vestibule revealed the upregulation of immune-related genes and the downregulation of genes associated with ossification and nervous system development. A comparison with the isolated cochlear sensorineural structures showed similar changes in genes related to immune response, chondrocyte differentiation, and myelin formation. These findings suggest that age-related vestibular hypofunction is linked to diminished peripheral vestibular responses, likely due to the loss of a specific subpopulation of hair cells and calyceal afferents. The upregulation of immune- and inflammation-related genes implies that inflammation contributes to these functional and structural changes. Furthermore, the comparison of gene expression between the vestibule and cochlea indicates both shared and distinct mechanisms contributing to age-related vestibular and hearing impairments. Further research is necessary to understand the mechanistic connection between inflammation and age-related balance and hearing disorders and to translate these findings into clinical treatment strategies. |
| first_indexed | 2024-03-10T22:59:26Z |
| format | Article |
| id | doaj.art-82b0ab3b2200478bb226f42d917a71f7 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T22:59:26Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-82b0ab3b2200478bb226f42d917a71f72023-11-19T09:46:49ZengMDPI AGBiomolecules2218-273X2023-09-01139142910.3390/biom13091429Functional, Morphological and Molecular Changes Reveal the Mechanisms Associated with Age-Related Vestibular LossVasiliki Georgia Paplou0Nick M. A. Schubert1Marcel van Tuinen2Sarath Vijayakumar3Sonja J. Pyott4Department of Otorhinolaryngology and Head/Neck Surgery, University Medical Center Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Otorhinolaryngology and Head/Neck Surgery, University Medical Center Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Otorhinolaryngology and Head/Neck Surgery, University Medical Center Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Biomedical Sciences, School of Medicine, Creighton University, Omaha, NE 68178, USADepartment of Otorhinolaryngology and Head/Neck Surgery, University Medical Center Groningen, 9713 GZ Groningen, The NetherlandsAge-related loss of vestibular function and hearing are common disorders that arise from the loss of function of the inner ear and significantly decrease quality of life. The underlying pathophysiological mechanisms are poorly understood and difficult to investigate in humans. Therefore, our study examined young (1.5-month-old) and old (24-month-old) C57BL/6 mice, utilizing physiological, histological, and transcriptomic methods. Vestibular sensory-evoked potentials revealed that older mice had reduced wave I amplitudes and delayed wave I latencies, indicating reduced vestibular function. Immunofluorescence and image analysis revealed that older mice exhibited a significant decline in type I sensory hair cell density, particularly in hair cells connected to dimorphic vestibular afferents. An analysis of gene expression in the isolated vestibule revealed the upregulation of immune-related genes and the downregulation of genes associated with ossification and nervous system development. A comparison with the isolated cochlear sensorineural structures showed similar changes in genes related to immune response, chondrocyte differentiation, and myelin formation. These findings suggest that age-related vestibular hypofunction is linked to diminished peripheral vestibular responses, likely due to the loss of a specific subpopulation of hair cells and calyceal afferents. The upregulation of immune- and inflammation-related genes implies that inflammation contributes to these functional and structural changes. Furthermore, the comparison of gene expression between the vestibule and cochlea indicates both shared and distinct mechanisms contributing to age-related vestibular and hearing impairments. Further research is necessary to understand the mechanistic connection between inflammation and age-related balance and hearing disorders and to translate these findings into clinical treatment strategies.https://www.mdpi.com/2218-273X/13/9/1429auditoryvestibularinner earpresbycusis or age-induced hearing lossbalance disordersaging |
| spellingShingle | Vasiliki Georgia Paplou Nick M. A. Schubert Marcel van Tuinen Sarath Vijayakumar Sonja J. Pyott Functional, Morphological and Molecular Changes Reveal the Mechanisms Associated with Age-Related Vestibular Loss Biomolecules auditory vestibular inner ear presbycusis or age-induced hearing loss balance disorders aging |
| title | Functional, Morphological and Molecular Changes Reveal the Mechanisms Associated with Age-Related Vestibular Loss |
| title_full | Functional, Morphological and Molecular Changes Reveal the Mechanisms Associated with Age-Related Vestibular Loss |
| title_fullStr | Functional, Morphological and Molecular Changes Reveal the Mechanisms Associated with Age-Related Vestibular Loss |
| title_full_unstemmed | Functional, Morphological and Molecular Changes Reveal the Mechanisms Associated with Age-Related Vestibular Loss |
| title_short | Functional, Morphological and Molecular Changes Reveal the Mechanisms Associated with Age-Related Vestibular Loss |
| title_sort | functional morphological and molecular changes reveal the mechanisms associated with age related vestibular loss |
| topic | auditory vestibular inner ear presbycusis or age-induced hearing loss balance disorders aging |
| url | https://www.mdpi.com/2218-273X/13/9/1429 |
| work_keys_str_mv | AT vasilikigeorgiapaplou functionalmorphologicalandmolecularchangesrevealthemechanismsassociatedwithagerelatedvestibularloss AT nickmaschubert functionalmorphologicalandmolecularchangesrevealthemechanismsassociatedwithagerelatedvestibularloss AT marcelvantuinen functionalmorphologicalandmolecularchangesrevealthemechanismsassociatedwithagerelatedvestibularloss AT sarathvijayakumar functionalmorphologicalandmolecularchangesrevealthemechanismsassociatedwithagerelatedvestibularloss AT sonjajpyott functionalmorphologicalandmolecularchangesrevealthemechanismsassociatedwithagerelatedvestibularloss |