title: Acrolein induces myelin damage in mammalian spinal cord.
abstract: Myelin damage can lead to the loss of axonal conduction and paralysis in multiple sclerosis and spinal cord injury. Here, we show that acrolein, a lipid peroxidation product, can cause significant myelin damage in isolated guinea pig spinal cord segments. Acrolein-mediated myelin damage is particularly conspicuous in the paranodal region in both a calcium dependent (nodal lengthening) and a calcium-independent manner (paranodal myelin splitting). In addition, paranodal protein complexes can dissociate with acrolein incubation. Degraded myelin basic protein is also detected at the paranodal region. Acrolein-induced exposure and redistribution of paranodal potassium channels and the resulting axonal conduction failure can be partially reversed by 4-AP, a potassium channel blocker. From this data, it is clear that acrolein is capable of inflicting myelin damage as well as axonal degeneration, and may represent an important factor in the pathogenesis in multiple sclerosis and spinal cord injury.
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana 47907, USA. riyi@purdue.edu
authors.forename: Yunzhou
authors.initials: Y
authors.lastname: Shi
authors.forename: Wenjing
authors.initials: W
authors.lastname: Sun
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: McBride
authors.forename: Ji-Xin
authors.initials: JX
authors.lastname: Cheng
authors.forename: Riyi
authors.initials: R
authors.lastname: Shi
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000171:Acrolein / Q000633:toxicity*; D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D004676:Myelin Basic Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009431:Neural Conduction / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism; D011901:Ranvier's Nodes / Q000187:drug effects; D013059:Spectrum Analysis, Raman; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects*
chemical_list: D015815:Cell Adhesion Molecules; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D000171:Acrolein; D015761:4-Aminopyridine; D002118:Calcium