Elevated zinc transporter ZnT3 in the dentate gyrus of mast cell‐deficient mice
Elevated zinc transporter ZnT3 in the dentate gyrus of mast cell‐deficient mice
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DOI：
10.1111/ejn.14575
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发表时间：
2020-03
影响因子：
3.4
通讯作者：
Amen Wiqas;J. LeSauter;A. Taub;R. Austin;R. Silver
中科院分区：
文献类型：
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作者：
Amen Wiqas;J. LeSauter;A. Taub;R. Austin;R. Silver
锌在神经发生中很重要，但过量会导致细胞凋亡和其他导致认知障碍的病变。肥大细胞存在于许多大脑区域，包括海马体，这是一个富含囊泡锌的区域。肥大细胞含有富锌颗粒和完善的锌离子摄取机制；这两个特征都表明锌在体内平衡中发挥作用的潜力。之前使用蒂姆染色的研究支持了这一假设，因为与野生型小鼠相比，在肥大细胞缺陷小鼠的海马体中检测到不稳定的锌增加，而两种基因型在整个大脑或其他组织中的总锌没有发现差异。本报告通过探索锌转运蛋白 ZnT3（将不稳定的锌转运至突触小泡），进一步研究了野生型和肥大细胞缺陷小鼠之间锌稳态的差异。第一项研究使用免疫细胞化学将 ZnT3 定位在海马体的苔藓纤维层内，以确定野生型小鼠与肥大细胞缺陷型小鼠中 ZnT3 的表达是否存在差异。第二项研究使用电感耦合等离子体质谱（ICP-MS）来测定两种基因型的整个齿状回中的总锌含量。免疫细胞化学结果表明，肥大细胞缺陷小鼠齿状回苔藓纤维层中的 ZnT3 水平高于野生型小鼠。 ICP-MS 数据显示整个齿状回的总锌含量没有差异。结果与肥大细胞在突触小泡水平参与锌稳态的假设一致。
Zinc is important in neurogenesis, but excessive levels can cause apoptosis and other pathologies leading to cognitive impairments. Mast cells are present in many brain regions including the hippocampus, an area rich in vesicular zinc. Mast cells contain zinc‐rich granules and a well‐developed mechanism for uptake of zinc ions; both features point to the potential for a role in zinc homeostasis. Prior work using the Timm stain supported this hypothesis, as increased labile zinc was detected in the hippocampus of mast cell‐deficient mice compared to wild‐type mice while no differences in total zinc were found between the two genotypes in the whole brain or other tissues. The current report further examines differences in zinc homeostasis between wild‐type and mast cell‐deficient mice by exploring the zinc transporter ZnT3, which transports labile zinc into synaptic vesicles. The first study used immunocytochemistry to localize ZnT3 within the mossy fibre layer of the hippocampus to determine whether there was differential expression of ZnT3 in wild‐type versus mast cell‐deficient mice. The second study used inductively coupled plasma mass spectrometry (ICP‐MS) to determine total zinc content in the whole dentate gyrus of the two genotypes. The immunocytochemical results indicate that there are higher levels of ZnT3 localized to the mossy fibre layer of the dentate gyrus of mast cell‐deficient mice than in wild‐type mice. The ICP‐MS data reveal no differences in total zinc in dentate gyrus as a whole. The results are consistent with the hypothesis that mast cells participate in zinc homeostasis at the level of synaptic vesicles.