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Repeated injuries dramatically affect cells of the oligodendrocyte lineage: Effects of PDGF and NT‐3 in vitro
Author(s) -
Fressinaud Catherine
Publication year - 2005
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.20136
Subject(s) - remyelination , oligodendrocyte , multiple sclerosis , platelet derived growth factor receptor , myelin , biology , platelet derived growth factor , progenitor cell , myelin basic protein , growth factor , neuroscience , microbiology and biotechnology , immunology , central nervous system , stem cell , receptor , biochemistry
In multiple sclerosis, relapses occur and remyelination is incomplete, whereas one demyelinating lesion induced by lysophosphatidyl choline (LPC) in rats is completely remyelinated; this process is accelerated by platelet‐derived growth factor (PDGF) (Allamargot et al.: Brain Res 918:28–39,2001) and neurotrophin‐3 (NT‐3) (Jean et al.: Brain Res 972:110–118,2003). Similarly, oligodendrocyte (OL) progenitors might not be depleted by two to three episodes of toxic demyelination (Penderis et al.: Brain 126:1382–1391,2003); nevertheless this does not allow conclusions about the fate of resident cells (mature OL). As myelinated fibers per OL are constantly decreased in chronic MS plaques (Fressinaud and Jean: J Neurochem 85(suppl):100,2003), this suggests that OL decreased capability to synthesize new myelin membranes could result from successive relapses, impairing thereby remyelination. Thus, we have determined the consequences of multiple versus unique (Fressinaud and Vallat: J Neurosci Res 38:202–213,1994) LPC treatments on newborn rat brain pure OL cultures, as well as the putative pro‐remyelinating effects of PDGF and of NT‐3 in these conditions. Split (0.5 · 10 −5 M, 6 h × 4) and multiple (2 · 10 −5 M, 24 h × 2) LPC doses induced more cell loss than a unique treatment (2 × 10 −5 M, 24 h) and there was no recovery. OL progenitors (A2B5+ cells) and differentiated (CNP+) OL were drastically decreased. Moreover, mature (MBP+) OL disappeared from these cultures, indicating that mature OL are also vulnerable to multiple insults. PDGF, as well as NT‐3, induced at least partial recovery, and enhanced OL progenitor proliferation. In cultures treated with either of these growth factors, mature OL represented one‐fourth of cells and extended numerous ramified processes and putative myelin balls. © 2004 Wiley‐Liss, Inc.