Loss of sestrin 2 potentiates the early onset of age-related sensory cell degeneration in the cochlea. (11th October 2017)

• Record Type: Journal Article
• Authors: Zhang, Celia; Sun, Wei; Li, Ji; Xiong, Binbin; Frye, Mitchell D.; Ding, Dalian; Salvi, Richard; Kim, Mi-Jung; Someya, Shinichi; Hu, Bo Hua
• Is Part Of: Neuroscience. Volume 361(2017)
• Page Start: 179
• Page End: 191
• Publication Date: 2017-10-11
• Subjects: ABR auditory brainstem response -- ARHL age-related hearing loss -- DAPI 4′, 6-diamidino-2′-phenylindole, dihydrochloride -- GAPDH glyceraldehyde-3-phosphate dehydrogenase -- KO knockout -- OHC outer hair cell -- PBS phosphate-buffered saline -- ROS reactive oxygen species -- RT-qPCR quantitative reverse transcriptase-polymerase chain reaction -- Tlr Toll-like receptor; sestrin 2 (SESN2) -- age-related hearing loss -- cochlea -- outer hair cells -- macrophages -- inflammation; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2017.08.015
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: SESN2 is expressed in the mouse cochlear sensory epithelium. Cochlear SESN2 expression decreases with aging. Loss of SESN2 function potentiates age-related cochlear degeneration. SESN2 deficiency provokes proinflammatory responses. Abstract: Sestrin 2 (SESN2) is a stress-inducible protein that protects tissues from oxidative stress and delays the aging process. However, its role in maintaining the functional and structural integrity of the cochlea is largely unknown. Here, we report the expression of SESN2 protein in the sensory epithelium, particularly in hair cells. Using C57BL/6J mice, a mouse model of age-related cochlear degeneration, we observed a significant age-related reduction in SESN2 expression in cochlear tissues that was associated with early onset hearing loss and accelerated age-related sensory cell degeneration that progressed from the base toward the apex of the cochlea. Hair cell death occurred by caspase-8 mediated apoptosis. Compared to C57BL/6J control mice, Sesn2 KO mice displayed enhanced expression of proinflammatory genes and activation of basilar membrane macrophages, suggesting that loss of SESN2 function provokes the immune response. Together, these results suggest that Sesn2 plays an important role in cochlear homeostasis and immune responses to stress.