Neuroprotective activation of astrocytes by methylmercury exposure in the inferior colliculus
Neuroprotective activation of astrocytes by methylmercury exposure in the inferior colliculus
复制标题
DOI：
10.1038/s41598-019-50377-9
复制
发表时间：
2019-09-25
影响因子：
4.6
通讯作者：
Yamazaki, Takeshi
中科院分区：
文献类型：
--
作者：
Ishihara, Yasuhiro;Itoh, Kouichi;Yamazaki, Takeshi
众所周知，甲基汞（MeHg）会引起听觉障碍，如构音障碍。当我们通过磁共振成像对暴露于甲基汞的小鼠大脑进行全面分析时，观察到位于听觉通路中的下丘（IC）的T1信号增加。因此，本研究的目的是探讨病理生理和听觉功能障碍的甲基汞引起的，重点是IC。听觉脑干反应的测量结果显示，与溶剂组小鼠相比，暴露于甲基汞4周的小鼠IC的潜伏期增加，阈值降低。暴露于甲基汞的小鼠在暴露6周后注意到不协调，这表明IC功能障碍比不协调更早发生。有神经元或小胶质细胞的活动的数量没有变化，而胶质细胞酸性蛋白，星形胶质细胞活性的标志物的表达，升高在IC的甲基汞暴露小鼠暴露4周后，表明星形胶质细胞增生发生在IC。用氟柠檬酸治疗抑制星形胶质细胞增生加重了听性脑干反应评估的IC的潜伏期和阈值。因此，IC中的星形胶质细胞被认为在听觉通路中起保护作用。星形胶质细胞暴露于甲基汞增加脑源性神经营养因子在IC的表达，表明星形胶质细胞脑源性神经营养因子是一种有效的保护剂在IC。这项研究表明，星形胶质细胞增生的IC可能是一种适应性反应，甲基汞毒性。甲基汞的总体毒性可以根据甲基汞介导的神经元损伤和星形胶质细胞保护反应之间的平衡来确定。
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.