Research Unit for Experimental Neurotraumatology, Department of Neurosurgery, Medical University of Graz, Graz, Austria.
J Neurotrauma. 2013 Jul 15;30(14):1232-42. doi: 10.1089/neu.2012.2596.
Microparticles are cell-derived, membrane-sheathed structures that are believed to shuttle proteins, mRNA, and miRNA to specific local or remote target cells. To date best described in blood, we now show that cerebrospinal fluid (CSF) contains similar structures that can deliver RNAs and proteins to target cells. These are, in particular, molecules associated with neuronal RNA granules and miRNAs known to regulate neuronal processes. Small RNA molecules constituted 50% of the shuttled ribonucleic acid. Using microarray analysis, we identified 81 mature miRNA molecules in CSF microparticles. Microparticles from brain injured patients were more abundant than in non-injured subjects and contained distinct genetic information suggesting that they play a role in the adaptive response to injury. Notably, miR-9 and miR-451 were differentially packed into CSF microparticles derived from patients versus non-injured subjects. We confirmed the transfer of genetic material from CSF microparticles to adult neuronal stem cells in vitro and a subsequent microRNA-specific repression of distinct genes. This first indication of a regulated transport of functional genetic material in human CSF may facilitate the diagnosis and analysis of cerebral modulation in an otherwise inaccessible organ.
微粒体是细胞衍生的、膜包裹的结构，被认为可以将蛋白质、mRNA 和 miRNA 转运到特定的局部或远程靶细胞。迄今为止，微粒体在血液中被描述得最为详细，我们现在表明，脑脊液（CSF）中也含有类似的结构，可以将 RNA 和蛋白质递送到靶细胞。这些结构特别与神经元 RNA 颗粒相关，并且已知 miRNA 可以调节神经元过程。小 RNA 分子构成了 50%的转运 RNA。通过微阵列分析，我们在 CSF 微粒体中鉴定出 81 种成熟的 miRNA 分子。来自脑损伤患者的微粒体比非损伤组更丰富，并且含有不同的遗传信息，表明它们在对损伤的适应性反应中发挥作用。值得注意的是，miR-9 和 miR-451 在源自患者和非损伤患者的 CSF 微粒体中被差异包装。我们在体外证实了遗传物质从 CSF 微粒体向成年神经元干细胞的转移，以及随后特定基因的 microRNA 特异性抑制。这首次表明在人 CSF 中存在功能遗传物质的调节转运，这可能有助于诊断和分析在其他情况下无法进入的器官的大脑调节。
