THYROID-HORMONE RECEPTOR ISOFORMS ARE SEQUENTIALLY EXPRESSED IN OLIGODENDROCYTE LINEAGE CELLS DURING RAT CEREBRAL DEVELOPMENT

In the mammalian brain, thyroid hormones regulate myelination. Their a ctions are mediated by interactions with nuclear receptors that functi on as ligand-regulated transcription factors. Two genes, alpha and bet a, encode different isoforms, of which only the beta and alpha 1 isofo rms are authentic nuclear triiodothyronine (T3)receptors (NT3R), in ag reement with the important role of T3 on myelination and oligodendrocy te generation, the presence of NT3Rs has been reported in oligodendroc ytes and their precursors. We and others have shown that both progenit ors and oligodendrocytes in vitro express the alpha 1 and alpha 2 isof orms, but the expression of the beta 1 isoform is confined to differen tiated oligodendrocytes, suggesting that they have different functions . To establish if this is the case during development in vivo, we have studied NT3R isoform expression in glial cells isolated by density gr adient centrifugation from rat brains of various ages. We report the p resence of the alpha 1 NT3R and its variant alpha 2, but not that of t he beta 1 isoform, in newborn rat glial progenitors. The pattern of ex pression of beta 1, both at the level of mRNA and protein, parallels t he increase in the number of oligodendrocytes, We found a significant change in the kinetic parameters of [I-125],T3 binding to NT3Rs in the se cells during the first month of life, consisting of an increase in the binding capacity that peaks with myelination, and a significative decrease in Kd that coincides with the snitch from the alpha. to the b eta 1 isoform, Thus, the expression of NT3R isoforms in the rat oligod endrocyte Lineage changes radically from the alpha to the beta 1 isofo rm during the period when oligodendrocytes differentiate from progenit ors, (C) 1998 Wiley-Liss, Inc.