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11 08, 2016;6 36306.

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
Author Information
  1. Nobutaka Ohgami: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya, Japan.
  2. Ichiro Yajima: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya, Japan.
  3. Machiko Iida: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya, Japan.
  4. Xiang Li: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya, Japan.
  5. Reina Oshino: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya, Japan.
  6. Mayuko Y Kumasaka: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya, Japan.
  7. Masashi Kato: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya, Japan.
PMID: 27824154 DOI: 10.1038/srep36306

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.

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MeSH Term

Aging
Animals
Disease Models, Animal
Hearing Loss
Hydroxylation
Hypoxia-Inducible Factor 1, alpha Subunit
Manganese
Mice
Mice, Transgenic
Nerve Degeneration
Phosphorylation
Proline
Proto-Oncogene Proteins c-ret
Spiral Ganglion
Up-Regulation

Chemicals

Hif1a protein, mouse
Hypoxia-Inducible Factor 1, alpha Subunit
Manganese
Proline
Proto-Oncogene Proteins c-ret
Ret protein, mouse
Journal Article Research Support, Non-U.S. Gov't

Word Cloud

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