Department of Neurobiology, University of Pittsburgh School of Medicine, USA; Department of Otolaryngology, University of Pittsburgh School of Medicine, USA; Pittsburgh Hearing Research Center, University of Pittsburgh School of Medicine, USA; Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh School of Medicine, USA.
Department of Otolaryngology, University of Pittsburgh School of Medicine, USA; Pittsburgh Hearing Research Center, University of Pittsburgh School of Medicine, USA.
Neuroscience. 2021 Mar 1;457:235-258. doi: 10.1016/j.neuroscience.2021.01.010. Epub 2021 Jan 16.
Nearly sixty years ago Fredrich Timm developed a histochemical technique that revealed a rich reserve of free zinc in distinct regions of the brain. Subsequent electron microscopy studies in Timm- stained brain tissue found that this "labile" pool of cellular zinc was highly concentrated at synaptic boutons, hinting a possible role for the metal in synaptic transmission. Although evidence for activity-dependent synaptic release of zinc would not be reported for another twenty years, these initial findings spurred decades of research into zinc's role in neuronal function and revealed a diverse array of signaling cascades triggered or regulated by the metal. Here, we delve into our current understanding of the many roles zinc plays in the brain, from influencing neurotransmission and sensory processing, to activating both pro-survival and pro-death neuronal signaling pathways. Moreover, we detail the many mechanisms that tightly regulate cellular zinc levels, including metal binding proteins and a large array of zinc transporters.
大约六十年前，弗雷德里希·蒂姆（Fredrich Timm）开发了一种组织化学技术，该技术揭示了大脑中不同区域中丰富的游离锌储备。随后，在 Timm 染色脑组织的电子显微镜研究中发现，这种“不稳定”的细胞锌池高度集中在突触末梢，暗示金属可能在突触传递中起作用。尽管在接下来的二十年中才会报道与活动相关的突触锌释放的证据，但这些最初的发现激发了数十年的研究，以探讨锌在神经元功能中的作用，并揭示了金属触发或调节的多种信号级联反应。在这里，我们深入探讨了锌在大脑中的许多作用，包括影响神经传递和感觉处理，激活生存和死亡神经元信号通路。此外，我们详细介绍了许多严格调节细胞锌水平的机制，包括金属结合蛋白和大量锌转运蛋白。
