Manganese-mediated acceleration of age-related hearing loss in mice

Nobutaka Ohgami, Ichiro Yajima, Machiko Iida, Xiang Li, Reina Oshino, Mayuko Y. Kumasaka, Masashi Kato

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Despite the fact that manganese (Mn) is known to be a neurotoxic element relevant to age-related disorders, the risk of oral exposure to Mn for age-related hearing loss remains unclear. In this study, we orally exposed wild-type young adult mice to Mn (Mn-exposed WT-mice) at 1.65 and 16.50 mg/L for 4 weeks. Mn-exposed WT-mice showed acceleration of age-related hearing loss. Mn-exposed WT-mice had neurodegeneration of spiral ganglion neurons (SGNs) with increased number of lipofuscin granules. Mn-exposed WT-mice also had increased hypoxia-inducible factor-1 alpha (Hif-1α) protein with less hydroxylation at proline 564 and decreased c-Ret protein in SGNs. Mn-mediated acceleration of age-related hearing loss involving neurodegeneration of SGNs was rescued in RET-transgenic mice carrying constitutively activated RET. Thus, oral exposure to Mn accelerates age-related hearing loss in mice with Ret-mediated neurodegeneration of SGNs.

Original languageEnglish
Article number36306
JournalScientific Reports
Publication statusPublished - 2016 Nov 8
Externally publishedYes


ASJC Scopus subject areas

  • General

Cite this

Ohgami, N., Yajima, I., Iida, M., Li, X., Oshino, R., Kumasaka, M. Y., & Kato, M. (2016). Manganese-mediated acceleration of age-related hearing loss in mice. Scientific Reports, 6, [36306].