title: Modulation of central nervous system-specific microRNA-124a alters the inflammatory response in the formalin test in mice.
abstract: microRNAs (miRNAs) are small noncoding RNAs that have been linked to a number of disease-related signal transduction pathways. Several studies indicate that they are also involved in nociception. It is not clear, however, which miRNAs are important and which genes are modulated by miRNA-associated mechanisms. This study focuses on the regulation and function of the central nervous system (CNS)-specific miRNA-124a in the spinal cord of mice in a formalin model of inflammatory nociception. miRNA-124a is constitutively expressed in the spinal cord of mice, particularly in neurons of the dorsal horn. Peripheral noxious stimulation with formalin led to significant down-regulation of its expression. Knock-down of miRNA-124a by intravenous administration of a specific miRNA-124a inhibitor further increased the nociceptive behavior associated with an upregulation of the pain-relevant miRNA-124a target MeCP2 and proinflammatory marker genes. In contrast, administration of a miRNA-124a mimic counteracted these effects and decreased nociception by down-regulation of the target gene. In conclusion, our results indicate that miRNA-124a is involved in inflammatory nociception by regulation of relevant target proteins and might therefore constitute a novel target for anti-inflammatory therapy.
authors: pharmazentrum frankfurt/ZAFES, Institut für Klinische Pharmakologie, Klinikum der Goethe-Universität Frankfurt, Frankfurt am Main, Germany.
authors: Katharina L
authors: KL
authors: Kynast
authors: Otto Quintus
authors: OQ
authors: Russe
authors: Christine V
authors: CV
authors: Möser
authors: Gerd
authors: G
authors: Geisslinger
authors: Ellen
authors: E
authors: Niederberger
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics; D005557:Formaldehyde / Q000633:toxicity; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D058990:Molecular Targeted Therapy; D009843:Oligoribonucleotides / Q000494:pharmacology; D010146:Pain / Q000209:etiology / Q000517:prevention & control; D058748:Pain Perception / Q000187:drug effects / Q000502:physiology*; D020671:Posterior Horn Cells / Q000378:metabolism; D012330:RNA, Double-Stranded / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D016037:Single-Blind Method; D013116:Spinal Cord / Q000378:metabolism* / Q000503:physiopathology; D014162:Transfection
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D035683:MicroRNAs; C540079:Mirn124 microRNA, mouse; D009843:Oligoribonucleotides; D012330:RNA, Double-Stranded; D005557:Formaldehyde