Glial Cells and Their Function in the Adult Brain: A Journey through the History of Their Ablation.

Glial Cells and Their Function in the Adult Brain: A Journey through the History of Their Ablation.
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DOI:
10.3389/fncel.2017.00024
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发表时间:
2017
影响因子:
5.3
通讯作者:
Dimou L
Dimou L
中科院分区:
医学2区
文献类型:
--
作者:
Jäkel S;Dimou L

文献摘要

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以小胶质细胞、星形胶质细胞和少突胶质细胞系细胞为主要成分的神经胶质细胞构成了哺乳动物大脑的很大一部分。最初被认为是神经元的纯粹无功能胶,几十年的研究强调了胶质细胞的重要性及其进一步的功能。尽管这些细胞的许多方面现在已经被很好地表征,但在生理和病理条件下,大脑中不同胶质细胞群的功能仍然没有解决,至少在一定程度上没有解决。为了解决这些重要的问题,已经开发了广泛的消耗方法,其中小胶质细胞,星形胶质细胞或少突胶质细胞谱系细胞(即ng2胶质细胞和少突胶质细胞)从成人脑网络中特异性地切除,并随后分析其后果。由于不同的胶质细胞群具有很大的异质性,因此必须特异性地消融单个细胞群,而不是在所有胶质细胞中诱导细胞死亡。由于现代的基因操作方法,这种方法现在可以直接针对感兴趣的细胞类型,使消融比以前使用的一般细胞消融方法更具特异性。在这篇综述中,我们将详细总结不同的神经胶质消融研究,重点是成年小鼠中枢神经系统和功能读数。我们还将展望如何在未来进一步利用这些方法。
Glial cells, consisting of microglia, astrocytes, and oligodendrocyte lineage cells as their major components, constitute a large fraction of the mammalian brain. Originally considered as purely non-functional glue for neurons, decades of research have highlighted the importance as well as further functions of glial cells. Although many aspects of these cells are well characterized nowadays, the functions of the different glial populations in the brain under both physiological and pathological conditions remain, at least to a certain extent, unresolved. To tackle these important questions, a broad range of depletion approaches have been developed in which microglia, astrocytes, or oligodendrocyte lineage cells (i.e., NG2-glia and oligodendrocytes) are specifically ablated from the adult brain network with a subsequent analysis of the consequences. As the different glial populations are very heterogeneous, it is imperative to specifically ablate single cell populations instead of inducing cell death in all glial cells in general. Thanks to modern genetic manipulation methods, the approaches can now directly be targeted to the cell type of interest making the ablation more specific compared to general cell ablation approaches that have been used earlier on. In this review, we will give a detailed summary on different glial ablation studies, focusing on the adult mouse central nervous system and the functional readouts. We will also provide an outlook on how these approaches could be further exploited in the future.