Platelet-derived growth factor partly prevents chemically induced oligodendrocyte death and improves myelin-like membranes repair in vitro.
We have previously shown that pure oligodendrocyte (OL) secondary cultures derived from newborn rat brain, in which cells form myelin-like membranes, can be used as a model to investigate the putative role of growth factors in myelin repair. After disruption of these membranes by lysophosphatidylcholine (LPC), a 3 day treatment with 10 ng/ml basic fibroblast growth factor (bFGF) induced reconstruction of myelin figures, albeit less compacted than in untreated controls. Here we show that in LPC treated cultures: 1) bFGF can not prevent OL from LPC-induced cell death; 2) platelet-derived growth factor (PDGF) pretreatment although preventing some cell death does not improve recovery compared to delayed treatment; 3) PDGF is as potent as bFGF in terms of O-2A progenitor proliferation; 4) PDGF is far more effective than bFGF, inducing the reappearance of more myelin-like structures with a better compaction; 5) there is no potentiation between these growth factors; and 6) after withdrawal of bFGF the compaction of myelin figures partly increases. These results indicate that PDGF, probably by inducing O-2A progenitors to proliferate and then allowing them to differentiate into mature myelinating OL, is a better candidate than bFGF to participate in myelin repair mechanisms in the central nervous system.
Fressinaud
C
C
Neurology Department, University Hospital, Angers, France.
Vallat
J M
JM
Pouplard-Barthelaix
A
A
D000818:Animals; D000831:Animals, Newborn; D000963:Antimetabolites / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D007150:Immunohistochemistry; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D008566:Membranes / Q000187:drug effects / Q000648:ultrastructure; D008854:Microscopy, Electron; D009186:Myelin Sheath / Q000187:drug effects* / Q000648:ultrastructure; D009836:Oligodendroglia / Q000187:drug effects* / Q000648:ultrastructure; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D051381:Rats; D013234:Stem Cells / Q000187:drug effects / Q000648:ultrastructure
D000963:Antimetabolites; D008244:Lysophosphatidylcholines; D010982:Platelet-Derived Growth Factor; D016222:Fibroblast Growth Factor 2; D001973:Bromodeoxyuridine