Zinc transporter 3 modulates cell proliferation and neuronal differentiation in the adult hippocampus,STEM CELLS

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Zinc transporter 3 modulates cell proliferation and neuronal differentiation in the adult hippocampus
STEM CELLS ( IF 4.0 ) Pub Date : 2020-05-07 , DOI: 10.1002/stem.3194
Bo Young Choi ₁ , Dae Ki Hong ₁ , Jeong Hyun Jeong ₁ , Bo Eun Lee ₁ , Jae-Young Koh ₂ , Sang Won Suh ₁

Affiliation

The subgranular zone of the dentate gyrus is a subregion of the hippocampus that has two uniquely defining features; it is one of the most active sites of adult neurogenesis as well as the location where the highest concentrations of synaptic zinc are found, the mossy fiber terminals. Therefore, we sought to investigate the idea that vesicular zinc plays a role as a modulator of hippocampal adult neurogenesis. Here, we used ZnT3−/− mice, which are depleted of synaptic‐vesicle zinc, to test the effect of targeted deletion of this transporter on adult neurogenesis. We found that this manipulation reduced progenitor cell turnover as well as led to a marked defect in the maturation of newborn cells that survive in the DG toward a neuronal phenotype. We also investigated the effects of zinc (ZnCl2), n‐acetyl cysteine (NAC), and ZnCl2 plus 2NAC (ZN) supplement on adult hippocampal neurogenesis. Compared with ZnCl2 or NAC, administration of ZN resulted in an increase in proliferation of progenitor cells and neuroblast. ZN also rescued the ZnT3 loss‐associated reduction of neurogenesis via elevation of insulin‐like growth factor‐1 and ERK/CREB activation. Together, these findings reveal that ZnT3 plays a highly important role in maintaining adult hippocampal neurogenesis and supplementation by ZN has a beneficial effect on hippocampal neurogenesis, as well as providing a therapeutic target for enhanced neuroprotection and repair after injury as demonstrated by its ability to prevent aging‐dependent cognitive decline in ZnT3−/− mice. Therefore, the present study suggests that ZnT3 and vesicular zinc are essential for adult hippocampal neurogenesis.

中文翻译：

锌转运蛋白 3 调节成年海马中的细胞增殖和神经元分化

齿状回的颗粒下区是海马体的一个亚区，具有两个独特的特征：它是成人神经发生最活跃的部位之一，也是发现突触锌浓度最高的地方，苔藓纤维末端。因此，我们试图研究泡状锌作为海马成体神经发生调节剂的作用。在这里，我们使用耗尽突触小泡锌的 ZnT3-/- 小鼠来测试该转运蛋白的靶向缺失对成人神经发生的影响。我们发现这种操作减少了祖细胞的更新，并导致在 DG 中存活的新生细胞向神经元表型的成熟过程中出现明显缺陷。我们还研究了锌 (ZnCl2)、n-乙酰半胱氨酸 (NAC)、和 ZnCl2 加 2NAC (ZN) 对成人海马神经发生的补充。与 ZnCl2 或 NAC 相比，ZN 的施用导致祖细胞和成神经细胞的增殖增加。ZN 还通过升高胰岛素样生长因子-1 和 ERK/CREB 激活来挽救与 ZnT3 丢失相关的神经发生减少。总之，这些发现表明 ZnT3 在维持成年海马神经发生中起着非常重要的作用，补充 ZN 对海马神经发生有有益作用，并为增强神经保护和损伤后修复提供治疗靶点，正如其预防能力所证明的那样。 ZnT3-/- 小鼠的衰老依赖性认知能力下降。因此，本研究表明 ZnT3 和囊泡锌对于成人海马神经发生至关重要。

更新日期：2020-05-07

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