Lysolecithin induces demyelination in vitro in a cerebellar slice culture system.
Demyelination is a hallmark of several human diseases, including multiple sclerosis. To understand better the process of demyelination and remyelination, we explored the use of an in vitro organotypic cerebellar slice culture system. Parasagittal slices of postnatal Day 10 (P10) rat cerebella cultured in vitro demonstrated significant myelination after 1 week in culture. Treatment of the cultures at 7 days in vitro (DIV) with the bioactive lipid lysolecithin (lysophosphatidylcholine) for 15-17 hr in vitro produced marked demyelination. This demyelination was observed by immunostaining for the myelin components myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG), and 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNPase). After a transient demyelinating insult with lysolecithin in vitro, the cultures recovered with oligodendrocyte differentiation recapitulating a normal time course; there was initially re-expression of CNPase and MBP during this recovery, and this was followed by MOG. In addition, there seemed to be some limited remyelination during the recovery phase. Lysolecithin thus induces demyelination in an in vitro organotypic cerebellar slice culture system, providing a model system for studying myelination, demyelination, and remyelination in vitro.
Birgbauer
Eric
E
Department of Neurobiology, Merck Research Laboratories, San Diego, California, USA. ericbirg@scripps.edu
Rao
Tadimeti S
TS
Webb
Michael
M
D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; D000818:Animals; D064026:Calbindins; D002531:Cerebellum / Q000187:drug effects / Q000502:physiology; D046508:Culture Techniques; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000503:physiopathology*; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D004676:Myelin Basic Protein / Q000378:metabolism; D009185:Myelin Proteins; D009186:Myelin Sheath / Q000187:drug effects / Q000502:physiology*; D018992:Myelin-Associated Glycoprotein / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000502:physiology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000502:physiology; D064030:S100 Calcium Binding Protein G / Q000378:metabolism
D064026:Calbindins; D008244:Lysophosphatidylcholines; C571326:MOG protein, human; C571328:Mog protein, rat; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D064030:S100 Calcium Binding Protein G; C051774:neurofilament protein H; D010727:Phosphoric Diester Hydrolases; D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; C571337:CNP protein, human; C571339:Cnp protein, rat