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Accumulating evidence has demonstrated that Wnt\/\u03b2\u2010catenin 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 <jats:sc>d<\/jats:sc>\u2010galactose (<jats:sc>d<\/jats:sc>\u2010gal), and explored changes in Wnt\/\u03b2\u2010catenin signaling in the auditory cortex. A decrease in Wnt\/\u03b2\u2010catenin signaling in the auditory cortex was found in both naturally aging and <jats:sc>d<\/jats:sc>\u2010gal\u2010mimetic aging rats, as indicated by increased <jats:styled-content style=\"fixed-case\">GSK<\/jats:styled-content>3\u03b2 activity and decreased \u03b2\u2010catenin activity. Moreover, lithium chloride (Licl), an activator of Wnt signaling pathway, was administered long term to 15\u2010month\u2010old <jats:sc>d<\/jats:sc>\u2010gal\u2010treated rats. Activation of Wnt\/\u03b2\u2010catenin signaling by Licl attenuated <jats:sc>d<\/jats:sc>\u2010gal\u2010induced auditory cortex apoptosis and neurodegeneration. Bmi1, a transcription factor implicated in antiaging and resistance to apoptosis, can be modulated by \u03b2\u2010catenin activity. Here, we showed that the expression of Bmi1 was reduced and the expression of its downstream genes, <jats:italic>p16<\/jats:italic><jats:styled-content style=\"fixed-case\"><jats:sup><jats:italic>INK<\/jats:italic><\/jats:sup><\/jats:styled-content><jats:sup><jats:italic>4a<\/jats:italic><\/jats:sup>, <jats:italic>p19<\/jats:italic><jats:sup><jats:italic>Arf<\/jats:italic><\/jats:sup>, and <jats:italic>p53<\/jats:italic> were increased in the auditory cortex both of naturally aging and <jats:sc>d<\/jats:sc>\u2010gal\u2010mimetic aging rats. In addition, Licl significantly increased Bmi1 expression and reduced p16<jats:styled-content style=\"fixed-case\"><jats:sup>INK<\/jats:sup><\/jats:styled-content><jats:sup>4a<\/jats:sup>, p19<jats:sup>Arf<\/jats:sup>, and p53 expression. Our results indicated that decreased Wnt\/\u03b2\u2010catenin signaling might participate in the pathogenesis of central presbycusis through modulating the expression of Bmi1. Wnt\/\u03b2\u2010catenin signaling might be used as a potential therapeutic target against presbycusis.<\/jats:p>","DOI":"10.1002\/2211-5463.12220","type":"journal-article","created":{"date-parts":[[2017,3,23]],"date-time":"2017-03-23T06:24:59Z","timestamp":1490250299000},"page":"759-776","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Activation of Wnt\/\u03b2\u2010catenin signaling by lithium chloride attenuates <scp>d<\/scp>\u2010galactose\u2010induced neurodegeneration in the auditory cortex of a rat model of aging"],"prefix":"10.1002","volume":"7","author":[{"given":"Ming\u2010Yu","family":"Xia","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 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