More than cell dust: microparticles isolated from cerebrospinal fluid of brain injured patients are messengers carrying mRNAs, miRNAs, and proteins.
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.
Research Unit for Experimental Neurotraumatology, Department of Neurosurgery, Medical University of Graz, Graz, Austria.
Silke
S
Patz
Christa
C
Trattnig
Gerda
G
Grünbacher
Birgit
B
Ebner
Christian
C
Gülly
Alexandra
A
Novak
Beate
B
Rinner
Gerd
G
Leitinger
Markus
M
Absenger
Oana A
OA
Tomescu
Gerhard G
GG
Thallinger
Ulrike
U
Fasching
Sonja
S
Wissa
Juan
J
Archelos-Garcia
Ute
U
Schäfer
D000328:Adult; D000368:Aged; D015153:Blotting, Western; D001930:Brain Injuries / Q000134:cerebrospinal fluid* / Q000378:metabolism*; D002460:Cell Line; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D019295:Computational Biology; D005260:Female; D005434:Flow Cytometry; D020868:Gene Silencing; D015600:Glasgow Coma Scale; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008854:Microscopy, Electron; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism*
D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger