LPA-mediated demyelination in ex vivo culture of dorsal root.
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.
Fujita
Ryousuke
R
Division of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.
Kiguchi
Norikazu
N
Ueda
Hiroshi
H
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
D008246:Lysophospholipids; D004676:Myelin Basic Protein; D018993:Myelin P0 Protein; D049368:Receptors, Lysophosphatidic Acid; D014048:Tolonium Chloride; C032881:lysophosphatidic acid