Open Access

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

  • Authors:
    • Jie Yuan
    • Xueyan Zhao
    • Yujuan Hu
    • Haiying Sun
    • Guoqing Gong
    • Xiang Huang
    • Xubo Chen
    • Mingyu Xia
    • Chen Sun
    • Qilin Huang
    • Yu Sun
    • Wen Kong
    • Weijia Kong
  • View Affiliations

  • Published online on: January 17, 2018     https://doi.org/10.3892/ijmm.2018.3393
  • Pages: 2086-2098
  • Copyright: © Yuan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.
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April-2018
Volume 41 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Copy and paste a formatted citation
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Spandidos Publications style
Yuan J, Zhao X, Hu Y, Sun H, Gong G, Huang X, Chen X, Xia M, Sun C, Huang Q, Huang Q, et al: Autophagy regulates the degeneration of the auditory cortex through the AMPK-mTOR-ULK1 signaling pathway. Int J Mol Med 41: 2086-2098, 2018
APA
Yuan, J., Zhao, X., Hu, Y., Sun, H., Gong, G., Huang, X. ... Kong, W. (2018). Autophagy regulates the degeneration of the auditory cortex through the AMPK-mTOR-ULK1 signaling pathway. International Journal of Molecular Medicine, 41, 2086-2098. https://doi.org/10.3892/ijmm.2018.3393
MLA
Yuan, J., Zhao, X., Hu, Y., Sun, H., Gong, G., Huang, X., Chen, X., Xia, M., Sun, C., Huang, Q., Sun, Y., Kong, W., Kong, W."Autophagy regulates the degeneration of the auditory cortex through the AMPK-mTOR-ULK1 signaling pathway". International Journal of Molecular Medicine 41.4 (2018): 2086-2098.
Chicago
Yuan, J., Zhao, X., Hu, Y., Sun, H., Gong, G., Huang, X., Chen, X., Xia, M., Sun, C., Huang, Q., Sun, Y., Kong, W., Kong, W."Autophagy regulates the degeneration of the auditory cortex through the AMPK-mTOR-ULK1 signaling pathway". International Journal of Molecular Medicine 41, no. 4 (2018): 2086-2098. https://doi.org/10.3892/ijmm.2018.3393