title: LPA-mediated demyelination in ex vivo culture of dorsal root.
abstract: Lysophosphatidic acid (LPA) causes neuropathic pain with demyelination in sensory fibers. In dorsal root (DR) ex vivo culture, the addition of 0.1 microM LPA caused a characteristic demyelination at 24h in scanning and transmission electron microscopy analyses. Moreover, direct contact between C-fibers due to loss of partition by Schwann cell in Remak bundles was observed. LPA-induced demyelination of DR was concentration-dependent in the range between 0.01 and 1M, and was abolished by BoNT/C3 and Y-27632, a RhoA and Rho kinase inhibitor, respectively. The demyelination was equivalent between the preparations with and without dorsal root ganglion. LPA also caused a down-regulation of myelin proteins, such as myelin basic protein (MBP) and myelin protein zero (MPZ) to approximately 70% of control. All these findings suggest that the demyelination observed in the neuropathic pain due to nerve injury occurs through a direct action of LPA on Schwann cells.
authors.affiliation: Division of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.
authors.forename: Ryousuke
authors.initials: R
authors.lastname: Fujita
authors.forename: Norikazu
authors.initials: N
authors.lastname: Kiguchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ueda
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D003711:Demyelinating Diseases / Q000473:pathology*; D006930:Hyperalgesia / Q000473:pathology; D008246:Lysophospholipids / Q000494:pharmacology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D004676:Myelin Basic Protein / Q000378:metabolism; D018993:Myelin P0 Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000187:drug effects*; D009412:Nerve Fibers / Q000187:drug effects; D010146:Pain / Q000503:physiopathology; D049368:Receptors, Lysophosphatidic Acid / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D012583:Schwann Cells / Q000187:drug effects; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013126:Spinal Nerve Roots / Q000166:cytology*; D014048:Tolonium Chloride
chemical_list: D008246:Lysophospholipids; D004676:Myelin Basic Protein; D018993:Myelin P0 Protein; D049368:Receptors, Lysophosphatidic Acid; D014048:Tolonium Chloride; C032881:lysophosphatidic acid