Journal
FEBS OPEN BIO
Volume 7, Issue 6, Pages 759-776Publisher
WILEY
DOI: 10.1002/2211-5463.12220
Keywords
aging; auditory cortex; Bmil; presbycusis; Wnt/beta-catenin signaling
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Funding
- National Natural Science Foundation of China [81230021]
- Major State Basic Research Development Program of China (973 program) [2011CB504504]
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Degeneration of the central auditory system, which is characterized by reduced understanding of speech and source localization of sounds, is an important cause of age-related hearing loss (presbycusis). Accumulating evidence has demonstrated that Wnt/beta-catenin signaling plays an essential role in the development of the auditory system but its potential role in presbycusis remains unclear. In this study, we used a rat model of aging, created by chronic systemic exposure to D-galactose (D-gal), and explored changes in Wnt/beta-catenin signaling in the auditory cortex. A decrease in Wnt/beta-catenin signaling in the auditory cortex was found in both naturally aging and D-gal-mimetic aging rats, as indicated by increased GSK3 beta activity and decreased beta-catenin activity. Moreover, lithium chloride (Licl), an activator of Wnt signaling pathway, was administered long term to 15-month-old D-gal-treated rats. Activation of Wnt/beta-catenin signaling by Licl attenuated D-gal-induced auditory cortex apoptosis and neurodegeneration. Bmil, a transcription factor implicated in antiaging and resistance to apoptosis, can be modulated by beta-catenin activity. Here, we showed that the expression of Bmil was reduced and the expression of its downstream genes, p16(INK4a), p19(Arf), and p53 were increased in the auditory cortex both of naturally aging and D-gal-mimetic aging rats. In addition, Licl significantly increased Bmil expression and reduced p16(INK4a), p19(Arf), and p53 expression. Our results indicated that decreased Wnt/beta-catenin signaling might participate in the pathogenesis of central presbycusis through modulating the expression of Bmil. Wnt/beta-catenin signaling might be used as a potential therapeutic target against presbycusis.
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