@article{14a8cf46811d4f6faebf66d334903c70,
title = "Manganese-mediated acceleration of age-related hearing loss in mice",
abstract = "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.",
author = "Nobutaka Ohgami and Ichiro Yajima and Machiko Iida and Xiang Li and Reina Oshino and Kumasaka, {Mayuko Y.} and Masashi Kato",
note = "Funding Information: This study was supported in part by Grants-in-Aid for Scientific Research on Innovative Areas (24108001, 16H01639), Scientific Research (A) (15H01743 and 15H02588), (B) (16H02962) and (C) (25460178, 16K08343), Grant-in-Aid for Challenging Exploratory Research (26670525) and center of excellence (COE) Project for Private Universities (Nutritional Health Science Research Center; No. S1201007) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Matching Planner Program (MP27115658214) from the Japan Science and Technology Agency (JST), the Japan Health Foundation, the Mitsui & Co., Ltd. Environment Fund, Foundation from Center for Advanced Medical and Clinical Research Nagoya University Hospital, the Mitsubishi Foundation, and the Research Foundation for Health Sciences (The KENKO-KAGAKU Zaidan). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: {\textcopyright} The Author(s) 2016.",
year = "2016",
month = nov,
day = "8",
doi = "10.1038/srep36306",
language = "English",
volume = "6",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
}