Manganese-mediated acceleration of age-related hearing loss in mice.
Manganese-mediated acceleration of age-related hearing loss in mice.
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DOI：
10.1038/srep36306
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发表时间：
2016-11-08
影响因子：
4.6
通讯作者：
Kato M
中科院分区：
文献类型：
--
作者：
Ohgami N;Yajima I;Iida M;Li X;Oshino R;Kumasaka MY;Kato M
尽管锰（Mn）是一种与年龄相关疾病相关的神经毒性元素，但口服Mn对年龄相关听力损失的风险仍不清楚。在这项研究中，我们口服暴露于锰（锰暴露WT小鼠）在1.65和16.50 mg/L的野生型年轻成年小鼠4周。锰暴露的WT小鼠表现出与年龄相关的听力损失的加速。锰暴露WT小鼠螺旋神经节神经元（SGNs）的神经变性与脂褐质颗粒的数量增加。锰暴露的WT小鼠也有增加的缺氧诱导因子-1 α（HIF-1α）蛋白，脯氨酸564处的羟基化较少，SGN中的c-Ret蛋白减少。锰介导的加速年龄相关性听力损失，涉及神经变性的SGNs获救的RET转基因小鼠携带组成性激活RET。因此，口服暴露于Mn加速了患有视网膜介导的SGN神经变性的小鼠的年龄相关性听力损失。
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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影响因子：
5.3
作者：
Kujawa, SG;Liberman, MC
通讯作者：
Liberman, MC
影响因子：
5.3
作者：
Lang, HN;Schulte, BA;Schmiedt, RA
通讯作者：
Schmiedt, RA
影响因子：
6.6
作者：
Menardo, Julien;Tang, Yong;Wang, Jing
通讯作者：
Wang, Jing
影响因子：
10.4
作者：
Bouchard MF;Sauvé S;Barbeau B;Legrand M;Brodeur MÈ;Bouffard T;Limoges E;Bellinger DC;Mergler D
通讯作者：
Mergler D
影响因子：
168.9
作者：
Gates, GA;Mills, JH
通讯作者：
Mills, JH