Program of Biomedical Science, Graduate School of Integrated Sciences for Life, Hiroshima University, Hiroshima, 739-8521, Japan.
Center for Health and the Environment, University of California, Davis, CA, 95616, USA.
Sci Rep. 2019 Sep 25;9(1):13899. doi: 10.1038/s41598-019-50377-9.
Methylmercury (MeHg) is well known to induce auditory disorders such as dysarthria. When we performed a global analysis on the brains of mice exposed to MeHg by magnetic resonance imaging, an increase in the T1 signal in the inferior colliculus (IC), which is localized in the auditory pathway, was observed. Therefore, the purpose of this study is to examine the pathophysiology and auditory dysfunction induced by MeHg, focusing on the IC. Measurement of the auditory brainstem response revealed increases in latency and decreases in threshold in the IC of mice exposed to MeHg for 4 weeks compared with vehicle mice. Incoordination in MeHg-exposed mice was noted after 6 weeks of exposure, indicating that IC dysfunction occurs earlier than incoordination. There was no change in the number of neurons or microglial activity, while the expression of glial fibrillary acidic protein, a marker for astrocytic activity, was elevated in the IC of MeHg-exposed mice after 4 weeks of exposure, indicating that astrogliosis occurs in the IC. Suppression of astrogliosis by treatment with fluorocitrate exacerbated the latency and threshold in the IC evaluated by the auditory brainstem response. Therefore, astrocytes in the IC are considered to play a protective role in the auditory pathway. Astrocytes exposed to MeHg increased the expression of brain-derived neurotrophic factor in the IC, suggesting that astrocytic brain-derived neurotrophic factor is a potent protectant in the IC. This study showed that astrogliosis in the IC could be an adaptive response to MeHg toxicity. The overall toxicity of MeHg might be determined on the basis of the balance between MeHg-mediated injury to neurons and protective responses from astrocytes.
甲基汞（MeHg）众所周知可诱发构音障碍等听觉障碍。我们通过磁共振成像对暴露于 MeHg 的小鼠大脑进行了全面分析，观察到位于听觉通路上的下丘（IC）中的 T1 信号增加。因此，本研究的目的是研究 MeHg 诱导的病理生理学和听觉功能障碍，重点研究 IC。与载体小鼠相比，暴露于 MeHg 4 周的小鼠的听觉脑干反应测量显示 IC 潜伏期延长，阈值降低。暴露于 MeHg 的小鼠在 6 周后出现协调障碍，表明 IC 功能障碍早于协调障碍。神经元数量或小胶质细胞活性没有变化，而暴露于 MeHg 的小鼠的 IC 中胶质纤维酸性蛋白（星形胶质细胞活性的标志物）的表达升高，表明 IC 中存在星形胶质细胞增生。用氟柠檬酸抑制星形胶质细胞增生可加重听觉脑干反应评估的 IC 潜伏期和阈值。因此，IC 中的星形胶质细胞被认为在听觉通路上起保护作用。暴露于 MeHg 的星形胶质细胞增加了 IC 中的脑源性神经营养因子的表达，表明 IC 中的星形胶质细胞脑源性神经营养因子是一种有效的保护剂。本研究表明，IC 中的星形胶质细胞增生可能是对 MeHg 毒性的适应性反应。MeHg 的总体毒性可能取决于神经元中 MeHg 介导的损伤与星形胶质细胞的保护反应之间的平衡。
