Geneeskundige Stichting Koningin Elisabeth ... - GSKE - FMRE

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A2B5, O4 and galactocerebroside immunophenotypes during in vitro oligodendrocyte maturation.We
show that glycine induces a specific dose-dependent mitogenic effect on A2B5-positive
OPCs which is suppressed by nifedipine, a L-type VGCC blocker. Although not completely
inhibiting this process at any stage, glycine also significantly decreases the rate of oligodendrocyte
differentiation. Without interfering with the in vitro survival of oligodendroglial cells, this
work supports our hypothesis that glycine can regulate oligodendrocyte development by a
mechanism involving a modulation of intracellular calcium homeostasis. Thus, glycine released
by neurons, as other neurotransmitters, might serve as a physiological signal between neurons
and OPCs during oligodendrogliogenesis. Pharmacological manipulations of this system might
also provide new pathways for remyelination strategies.
Since cyclin-dependent kinases (Cdks) and their endogenous inhibitors (CKIs) play an essential
role as regulators of cell cycle withdrawal and onset of differentiation within oligodendroglial
cells, we assessed here the effects of exogenous chemical CKIs on the proliferation , differentiation
and survival of cultured rat cortical oligodendrocyte progenitor cells (OPCs). We
demonstrated here that purine derivatives and especially roscovitine strongly inhibit PDGF-induced
OPCs proliferation. Roscovitine alone did not affect oligodendrocyte maturation wheras in
the presence of mitogenic signals and thyroid hormone, roscovitine increases the generation of
fully mature oligodendrocyte probably by triggering the appearance of cell cycle arrested-OPCs
that are then available to undergo the committing influence of thyroid hormone. Finally, we provided
evidence that antimitotic concentrations of roscovitine prevent from oligodendroglial
apoptosis induced by growth factor deprivation while concentrations much higher than the IC 50
value of its antiproliferative effect enhance apoptosis in PDGF-stimulated OPCs. We thus here
demonstrate by in vitro experiments that small molecular weight chemical CKIs, which are about
being tested in clinical trials for their chemotherapeutic properties, have important effects on oligodendroglial
development. This opens prospects for the potential use of these well tolerated
agents in remyelination strategies.
Study of developmental Neuronal Migration
Chanas-Sacré, G. 1 , Rogister, B. 1 , Nguyen, L. 1 , Thiry, M. 2 , Moonen, G. 1 and Leprince, P. 1
1 Centre de Neurobiologie Cellulaire et Moléculaire, Université de Liège, Belgique
2 Service de Biologie Cellulaire, Université de Liège, Belgique
Study of Radialin as an IFAP.
We have investigated the distribution of Radialin, the radial glia protein recognized by the
RC2 antibody in mouse embryos and have found that it is present outside of the CNS in forming
skeletal muscles (Leprince et al., 1999b). Radialin in muscle cells is also a 300 kDa protein
that, unlike the Radialin form in radial glia, is a soluble protein, allowing its characterization
and immunoprecipitation. We have compared the properties of Radialin with those of
other large MW IFAPS known to be expressed by glial cells during development (Leprince et
al., 2000). Of these, IFAP-300, Transitin, Plectin and Synemin differ from Radialin in either their
distribution, time of expression or immunoreactivity. Only Nestin, an intermediate filament pro-