3alpha,5alpha-Tetrahydroprogesterone (allopregnanolone) and gamma-aminobutyric acid: autocrine/paracrine interactions in the control of neonatal PSA-NCAM+ progenitor proliferation.

The earliest identified neonatal neural progenitors are cells that express the polysialylated form of the neural cell adhesion molecule (PSA-NCAM). One of these progenitors is the early PSA-NCAM+ progenitor (ePSA-NCAM+ progenitor; Gago et al. [2003] Mol Cell Neurosci 22:162-178), which corresponds to a multipotential cell with a default differentiation through glial lineages.

Osteopontin is upregulated during in vivo demyelination and remyelination and enhances myelin formation in vitro.

We have used in vitro oligodendrocyte differentiation and the in vivo remyelination model, the cuprizone model, to identify genes regulating oligodendrocyte function and remyelination. One of the genes we identified, osteopontin (opn), is a secreted glycoprotein with cytokine-like, chemotactic, and anti-apoptotic properties that contains an Arg-Gly-Asp (RGD) cell adhesion motif-mediating interactions with several integrins. Both microglia and astrocytes in demyelinating brain regions of cuprizone-fed mice expressed OPN protein.

Inducible expression of FGF2 by a rat oligodendrocyte precursor cell line promotes CNS myelination in vitro.

Transplantation of glial cells into the central nervous system (CNS) may be a promising approach for the treatment of myelin disorders such as multiple sclerosis (MS). Myelination by transplantation of oligodendrocyte precursors has been obtained in different animal models of demyelination. A strategy to favor CNS remyelination is to enrich the lesioned areas in growth factors to stimulate the quiescent population of oligodendrocyte precursors.

Control of cell survival and proliferation of postnatal PSA-NCAM(+) progenitors.

In the present work, we studied the effects of several growth factors on survival and proliferation of freshly isolated neural progenitors expressing the polysialylated form of neural cell adhesion molecule (PSA-NCAM). Cells were obtained from postnatal day 2 rat forebrain, using isolation method. We found that (1) insulin-like growth factor 1 (IGF-1) exerts a powerful survival effect by inhibiting apoptotic cell death, (2) epidermal growth factor (EGF) strongly increases cell proliferation, (3) the combination of IGF-1 plus EGF promotes cellular expansion, (4) basic fibroblast growth factor displays only a weak mitogenic effect, and (5) platelet-derived growth factor-AA (PDGF-AA) has no effect on cell survival and proliferation.

CNS integrins switch growth factor signalling to promote target-dependent survival.

Depending on the stage of development, a growth factor can mediate cell proliferation, survival or differentiation. The interaction of cell-surface integrins with extracellular matrix ligands can regulate growth factor responses and thus may influence the effect mediated by the growth factor. Here we show, by using mice lacking the alpha(6) integrin receptor for laminins, that myelin-forming oligodendrocytes activate an integrin-regulated switch in survival signalling when they contact axonal laminins.