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.

Nicotine increases serotonin release in the brain and symptoms of nicotine withdrawal may be modulated by diminished serotonergic neurotransmission. The promoter region of the serotonin transporter gene, solute carrier family neurotransmitter transporter member 4 (SLC6A4), contains a functional tandem repeat polymorphism. The long (L) variant is more actively transcribed than the short (S) variant and is associated with a higher serotonin uptake. To investigate the potential role of this polymorphism for smoking behavior, SLC6A4 genotypes were determined in two different studies, the SMOKING GENES case-control study (470 current smokers and 419 subjects who had never smoked) and the cross-sectional Ludwigshafen risk and cardiovascular health (LURIC) study (777 current smokers and 1178 subjects who had never smoked). In the SMOKING GENES case-control study, SLC6A4 genotype frequencies were not statistically different between smokers (LL: 30.9%; LS: 46.8%; SS: 16.4%) and non-smokers (LL: 36.3%; LS: 41.8%; SS: 14.3%; P ¼ 0.13). Similar results were obtained in the crosssectional LURIC study (smokers: LL, 36.5%, LS, 45.6%, SS, 17.9%; nonsmokers: LL, 33.6%, LS, 48.9%, SS, 17.6%; P ¼ 0.33). SLC6A4 genotypes were furthermore not associated with Fagerstrom Tolerance Questionnaire score, packyears, number of cigarettes smoked per day or previous attempts to quit smoking. We conclude that the SLC6A4 promoter polymorphism is not a major determinant of smoking behavior in Caucasian.

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Overall, LURIC data confirmed that there is no major cardiovascular risk associated with CYP2C8 and CYP2C9 variants in a cardiovascular risk population of patients having undergone coronary angiography.

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