Open AccessManganese-mediated acceleration of age-related hearing loss in mice
Author(s) -
Nobutaka Ohgami,
Ichiro Yajima,
Machiko Iida,
Xiang Li,
Reina Oshino,
Mayuko Kumasaka,
Masashi Kato
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep36306
Subject(s) - neurodegeneration , spiral ganglion , hearing loss , genetically modified mouse , endocrinology , transgene , medicine , lipofuscin , chemistry , biology , biochemistry , audiology , gene , disease
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.