A fluoro-Nissl dye identifies pericytes as distinct vascular mural cells during in vivo brain imaging.

A fluoro-Nissl dye identifies pericytes as distinct vascular mural cells during in vivo brain imaging.
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DOI:
10.1038/nn.4564
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发表时间:
2017-07
影响因子:
25
通讯作者:
Grutzendler J
Grutzendler J
中科院分区:
医学1区
文献类型:
--
作者:
Damisah EC;Hill RA;Tong L;Murray KN;Grutzendler J

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周细胞和平滑肌细胞是大脑微血管系统的组成部分。然而,不存在明确识别这些细胞类型的技术,极大地限制了它们的体内研究。在这里,我们展示了荧光尼氏染料 (NeuroTrace 500/525) 以精确的特异性标记大脑周细胞,从而可以在活体小鼠中进行高分辨率光学成像。我们证明毛细血管周细胞是一群具有独特形态、分子和功能特征的壁细胞,与毛细血管前或小动脉平滑肌肌动蛋白表达细胞不重叠。染料摄取的显着特异性表明周细胞具有其他脑细胞中不存在的分子运输机制。我们证明了在微血管发育和衰老过程中以及在脑缺血和阿尔茨海默病模型中进行纵向周细胞成像的可行性。在任何小鼠模型中轻松标记周细胞的能力开启了对血管发育、神经血管耦合和神经病理学中壁细胞进行广泛研究的可能性。
Pericytes and smooth muscle cells are integral components of the brain microvasculature. However, no techniques exist to unambiguously identify these cell types, greatly limiting their investigation in vivo. Here we show that a fluorescent Nissl dye (NeuroTrace 500/525) labels brain pericytes with exquisite specificity allowing high-resolution optical imaging in the live mouse. We demonstrate that capillary pericytes are a population of mural cells with distinct morphological, molecular, and functional features that do not overlap with pre-capillary or arteriolar smooth-muscle actin-expressing cells. The remarkable specificity for dye uptake suggests that pericytes have molecular transport mechanisms not present in other brain cells. We demonstrate feasibility for longitudinal pericyte imaging during microvascular development and aging and in models of brain ischemia and Alzheimer’s disease. The ability to easily label pericytes in any mouse model opens the possibility of a broad range of investigations of mural cells in vascular development, neurovascular coupling and neuropathology.
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