Department of Physiology, College of Medicine, Hallym University, Hallymdaehak-gil 1, Chuncheon, 24252, Republic of Korea.
Department of Pharmacology, College of Medicine, Hallym University, Hallymdaehak-gil 1, Chuncheon, 24252, Republic of Korea.
Mol Neurobiol. 2022 May;59(5):3206-3217. doi: 10.1007/s12035-022-02785-8. Epub 2022 Mar 15.
Zinc is an essential micronutrient required for proper function during neuronal development because it can modulate neuronal function and structure. A fully functional description of zinc in axonal processing in the central nervous system remains elusive. Here, we define the role of intracellular zinc in axon formation and elongation, involving the mammalian target of rapamycin complex 1 (mTORC1). To investigate the involvement of zinc in axon growth, we performed an ex vivo culture of mouse hippocampal neurons and administrated ZnCl as a media supplement. At 2 days in vitro, the administration of zinc induced the formation of multiple and elongated axons in the ex vivo culture system. A similar outcome was witnessed in callosal projection neurons in a developing mouse brain. Treatment with extracellular zinc activated the mTORC1 signaling pathway in mouse hippocampal neuronal cultures. The zinc-dependent enhancement of neuronal processing was inhibited either by the deactivation of mTORC1 with RAPTOR shRNA or by mTOR-insensitive 4EBP1 mutants. Additionally, zinc-dependent mTORC1 activation enhanced the axonal translation of TC10 and Par3 may be responsible for axonal growth. We identified a promising role of zinc in controlling axonogenesis in the developing brain, which, in turn, may indicate a novel structural role of zinc in the cytoskeleton and developing neurons.
锌是神经元发育过程中必需的微量元素，因为它可以调节神经元的功能和结构。锌在中枢神经系统轴突加工中的完全功能描述仍然难以捉摸。在这里，我们定义了细胞内锌在轴突形成和伸长中的作用，涉及哺乳动物雷帕霉素靶蛋白复合物 1（mTORC1）。为了研究锌在轴突生长中的作用，我们进行了体外培养的小鼠海马神经元实验，并将 ZnCl 作为培养基补充物进行添加。在体外培养的第 2 天，锌的添加诱导了体外培养系统中多个轴突的形成和伸长。在发育中的小鼠大脑中的胼胝体投射神经元中也观察到了类似的结果。在体外培养的小鼠海马神经元中，细胞外锌的处理激活了 mTORC1 信号通路。用 RAPTOR shRNA 使 mTORC1 失活或用 mTOR 不敏感的 4EBP1 突变体抑制锌依赖性增强神经元处理。此外，锌依赖性 mTORC1 激活增强了 TC10 和 Par3 的轴突翻译，这可能是轴突生长的原因。我们确定了锌在控制发育中大脑轴突发生中的有前景的作用，这反过来又可能表明锌在细胞骨架和发育中的神经元中具有新的结构作用。
