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Int J Mol Med. 2018 Apr;41(4):2086-2098. doi: 10.3892/ijmm.2018.3393. Epub 2018 Jan 17.

Autophagy regulates the degeneration of the auditory cortex through the AMPK-mTOR-ULK1 signaling pathway.

Author information

1
Department of Otolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
2
Department of Otolaryngology, Central Hospital of Huangshi, Huangshi, Hubei 435000, P.R. China.
3
Institute of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
4
Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.

Abstract

Presbycusis is the most common sensory impairment associated with aging; however, the underlying molecular mechanism remains unclear. Autophagy has been demonstrated to serve a key role in diverse diseases; however, no studies have examined its function in central presbycusis. The aim of the present study was to investigate the changes of autophagy in the physiological processes of the auditory cortex and its role in the degeneration of the auditory cortex, as well as the related mechanisms using naturally aging rats and a D‑galactose (D‑gal)‑induced mimetic rat model of aging. The present study demonstrated that autophagy increased from 3 months to 15 months in the normal saline (NS) control group, while it decreased in the D‑gal group. Compared with the age‑matched NS group, the D‑gal group demonstrated significantly increased levels of the autophagy‑related proteins, LC3 and Beclin 1 (BECN1) and the anti‑apoptotic proteins B‑cell lymphoma (BCL)2 and BCL‑extra large (BCL‑xL) at 3 months, with no obvious changes in cell apoptosis level and neuron ultrastructural morphology. However, LC3, BECN1, BCL2 and BCL‑xL were decreased at 15 months in the D-gal group, with cell apoptosis significantly increased and substantial neuron degeneration. Additionally, 5' AMP‑activated protein kinase (AMPK) activity was enhanced, and mechanistic target of rapamycin (mTOR) and ULK1 phosphorylation (Ser 757) activities were inhibited at 3 months compared with those of the NS group, while the opposite was observed at 9 and 15 months. The present results suggested that autophagy increases from young to adult and decreases at old age in the physiological processes of the auditory cortex, and has anti‑apoptotic as well as anti‑aging functions in the degeneration of the auditory cortex. Additionally, autophagy was regulated through AMPK activation and mTOR suppression, and impairment of autophagy may serve a key role in the degeneration of the auditory cortex, even in the pathogenesis of central presbycusis.

PMID:
29344647
PMCID:
PMC5810242
DOI:
10.3892/ijmm.2018.3393
[Indexed for MEDLINE]
Free PMC Article

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