Age-Related Hearing Loss in C57BL/6J Mice is Associated with Mitophagy Impairment in the Central Auditory System
Aging is associated with functional and morphological changes in the sensory organs, including the auditory system. Mitophagy, a process that regulates the turnover of dysfunctional mitochondria, is impaired with aging. This study aimed to investigate the effect of aging on mitophagy in the central...
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doaj-fa4fe4be294842b286a73b5a366f95f02020-11-25T03:55:39ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-09-01217202720210.3390/ijms21197202Age-Related Hearing Loss in C57BL/6J Mice is Associated with Mitophagy Impairment in the Central Auditory SystemCha Kyung Youn0Yonghyun Jun1Eu-Ri Jo2Sung Il Cho3Department of Premedical Science, Chosun University College of Medicine, Gwangju 61452, KoreaDepartment of Anatomy, Chosun University College of Medicine, Gwangju 61452, KoreaDepartment of Otolaryngology-Head and Neck Surgery, Chosun University College of Medicine, Gwangju 61452, KoreaDepartment of Otolaryngology-Head and Neck Surgery, Chosun University College of Medicine, Gwangju 61452, KoreaAging is associated with functional and morphological changes in the sensory organs, including the auditory system. Mitophagy, a process that regulates the turnover of dysfunctional mitochondria, is impaired with aging. This study aimed to investigate the effect of aging on mitophagy in the central auditory system using an age-related hearing loss mouse model. C57BL/6J mice were divided into the following four groups based on age: 1-, 6-, 12-, and 18-month groups. The hearing ability was evaluated by measuring the auditory brainstem response (ABR) thresholds. The mitochondrial DNA damage level and the expression of mitophagy-related genes, and proteins were investigated by real-time polymerase chain reaction and Western blot analyses. The colocalization of mitophagosomes and lysosomes in the mouse auditory cortex and inferior colliculus was analyzed by immunofluorescence analysis. The expression of genes involved in mitophagy, such as <i>PINK1</i>, <i>Parkin</i>, and <i>BNIP3</i> in the mouse auditory cortex and inferior colliculus, was investigated by immunohistochemical staining. The ABR threshold increased with aging. In addition to the mitochondrial DNA integrity, the mRNA levels of <i>PINK1</i>, <i>Parkin</i>, <i>NIX</i>, and <i>BNIP3</i>, as well as the protein levels of <i>PINK1</i>, <i>Parkin</i>, <i>BNIP3</i>, <i>COX4</i>, LC3B, mitochondrial oxidative phosphorylation (OXPHOS) subunits I–IV in the mouse auditory cortex significantly decreased with aging. The immunofluorescence analysis revealed that the colocalization of mitophagosomes and lysosomes in the mouse auditory cortex and inferior colliculus decreased with aging. The immunohistochemical analysis revealed that the expression of <i>PINK1</i>, <i>Parkin</i>, and <i>BNIP3</i> decreased in the mouse auditory cortex and inferior colliculus with aging. These findings indicate that aging-associated impaired mitophagy may contribute to the cellular changes observed in an aged central auditory system, which result in age-related hearing loss. Thus, the induction of mitophagy can be a potential therapeutic strategy for age-related hearing loss.https://www.mdpi.com/1422-0067/21/19/7202auditory cortexpresbycusisage-related hearing lossmitochondriamitophagy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Cha Kyung Youn Yonghyun Jun Eu-Ri Jo Sung Il Cho |
spellingShingle |
Cha Kyung Youn Yonghyun Jun Eu-Ri Jo Sung Il Cho Age-Related Hearing Loss in C57BL/6J Mice is Associated with Mitophagy Impairment in the Central Auditory System International Journal of Molecular Sciences auditory cortex presbycusis age-related hearing loss mitochondria mitophagy |
author_facet |
Cha Kyung Youn Yonghyun Jun Eu-Ri Jo Sung Il Cho |
author_sort |
Cha Kyung Youn |
title |
Age-Related Hearing Loss in C57BL/6J Mice is Associated with Mitophagy Impairment in the Central Auditory System |
title_short |
Age-Related Hearing Loss in C57BL/6J Mice is Associated with Mitophagy Impairment in the Central Auditory System |
title_full |
Age-Related Hearing Loss in C57BL/6J Mice is Associated with Mitophagy Impairment in the Central Auditory System |
title_fullStr |
Age-Related Hearing Loss in C57BL/6J Mice is Associated with Mitophagy Impairment in the Central Auditory System |
title_full_unstemmed |
Age-Related Hearing Loss in C57BL/6J Mice is Associated with Mitophagy Impairment in the Central Auditory System |
title_sort |
age-related hearing loss in c57bl/6j mice is associated with mitophagy impairment in the central auditory system |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2020-09-01 |
description |
Aging is associated with functional and morphological changes in the sensory organs, including the auditory system. Mitophagy, a process that regulates the turnover of dysfunctional mitochondria, is impaired with aging. This study aimed to investigate the effect of aging on mitophagy in the central auditory system using an age-related hearing loss mouse model. C57BL/6J mice were divided into the following four groups based on age: 1-, 6-, 12-, and 18-month groups. The hearing ability was evaluated by measuring the auditory brainstem response (ABR) thresholds. The mitochondrial DNA damage level and the expression of mitophagy-related genes, and proteins were investigated by real-time polymerase chain reaction and Western blot analyses. The colocalization of mitophagosomes and lysosomes in the mouse auditory cortex and inferior colliculus was analyzed by immunofluorescence analysis. The expression of genes involved in mitophagy, such as <i>PINK1</i>, <i>Parkin</i>, and <i>BNIP3</i> in the mouse auditory cortex and inferior colliculus, was investigated by immunohistochemical staining. The ABR threshold increased with aging. In addition to the mitochondrial DNA integrity, the mRNA levels of <i>PINK1</i>, <i>Parkin</i>, <i>NIX</i>, and <i>BNIP3</i>, as well as the protein levels of <i>PINK1</i>, <i>Parkin</i>, <i>BNIP3</i>, <i>COX4</i>, LC3B, mitochondrial oxidative phosphorylation (OXPHOS) subunits I–IV in the mouse auditory cortex significantly decreased with aging. The immunofluorescence analysis revealed that the colocalization of mitophagosomes and lysosomes in the mouse auditory cortex and inferior colliculus decreased with aging. The immunohistochemical analysis revealed that the expression of <i>PINK1</i>, <i>Parkin</i>, and <i>BNIP3</i> decreased in the mouse auditory cortex and inferior colliculus with aging. These findings indicate that aging-associated impaired mitophagy may contribute to the cellular changes observed in an aged central auditory system, which result in age-related hearing loss. Thus, the induction of mitophagy can be a potential therapeutic strategy for age-related hearing loss. |
topic |
auditory cortex presbycusis age-related hearing loss mitochondria mitophagy |
url |
https://www.mdpi.com/1422-0067/21/19/7202 |
work_keys_str_mv |
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