Increased expression of aquaporin-4 with methylmercury exposure in the brain of the common marmoset
Increased expression of aquaporin-4 with methylmercury exposure in the brain of the common marmoset
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DOI：
10.2131/jts.37.749
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发表时间：
2012-08-01
影响因子：
2
通讯作者：
Eto, Komyo
中科院分区：
文献类型：
--
作者：
Yamamoto, Megumi;Takeya, Motohiro;Eto, Komyo
目前尚不清楚甲基汞（MeHg）暴露与大脑中水通道蛋白（AQP）表达之间的关系。为了研究这一点，我们使用急性甲基汞暴露的常见狨猴模型来检查 AQP1、AQP4 和 AQP11 基因表达。给三只狨猴注射甲基汞（1.5 毫克汞/千克/天）14 天，然后 14 天不注射甲基汞。所有接受治疗的狨猴在处死前均表现出轻微的运动不能。在额叶、枕叶和小脑中，甲基汞施用后的总汞浓度分别为26.7、31.4和22.6μg/g。在枕叶中观察到轻微的细胞凋亡。免疫组织化学显示胶质纤维酸性蛋白、其 mRNA 和 Ibal 与 MeHg 的表达增加，表明神经元损伤激活了星形胶质细胞和小胶质细胞。对照组和MeHg给药组的额叶、枕叶或小脑中的AQP1蛋白或AQP11 mRNA没有显着差异。注射 MeHg 的狨猴中 AQP4 mRNA 表达与对照 (n = 3) 中平均 AQR4 表达的比率分别为 1.3、1.5 和 1.2、1.7、1.9 和 1.5，以及额叶、枕叶和小脑的 1.5、1.6 和 1.2。蛋白质印迹显示，MeHg 给药后枕叶和小脑中的 AQP4 蛋白显着增加，但额叶中没有明显上调。双染色免疫荧光分析显示，MeHg 给药组反应性星形胶质细胞细胞体中 AQP4 表达较低。这些结果表明，枕叶和小脑星形胶质细胞中的 MeHg 暴露可能会刺激 AQP4 的表达，这表明 AQP4 通过星形胶质细胞功能障碍在 MeHg 神经毒性中发挥作用。
The relationship between methylmercury (MeHg) exposure and aquaporin (AQP) expression in the brain is currently unknown. To investigate this, we used a common marmoset model of acute MeHg exposure to examine AQP1, AQP4 and AQP11 gene expression. MeHg (1.5 mg Hg/kg/day p.o.) was given to three marmosets for 14 days, followed by 14 days without. All treated marmosets showed slight akinesia before sacrifice. In the frontal lobe, occipital lobe and cerebellum, total mercury concentrations following MeHg administration were 26.7, 31.4, and 22.6 mu g/g, respectively. Slight apoptosis was observed in the occipital lobe. Immunohistochemistry showed increased expression of glial fibrillary acidic protein, its mRNA and Ibal with MeHg, indicating that neuronal injury activated astrocytes and microglia. There was no significant difference between control and MeHg-administered groups in AQP1 protein or AQP11 mRNA in the frontal lobe, occipital lobe or cerebellum. The ratio of AQP4 mRNA expression in MeHg-administered marmosets to the mean AQR4 expression in the controls (n = 3) were 1.3, 1.5 and 1.2, 1.7, 1.9 and 1.5, and 1.5, 1.6 and 1.2 for the frontal lobe, occipital lobe and cerebellum, respectively. Western blotting showed significantly increased AQP4 protein in the occipital lobe and cerebellum with MeHg administration, but no obvious up-regulation in the frontal lobe. Immunofluorescence analysis with double staining revealed low AQP4 expression in the cell body of reactive astrocytes in the MeHg-administered group. These results indicate that AQP4 expression might be stimulated by MeHg exposure in astrocytes in the occipital lobe and cerebellum, suggesting a role for AQP4 in MeHg neurotoxicity via astrocyte dysfunction.