OLIGODENDROCYTE MATURATION AND PROGENITOR-CELL PROLIFERATION ARE INDEPENDENTLY REGULATED BY THYROID-HORMONE

The development of oligodendrocyte progenitor cells is regulated by ep igenetic factors which control their proliferation and differentiation . When oligodendrocyte progenitor cells, purified on a Percoll centrif ugation gradient from neonate rat brain, are cultured in serum-free me dium in the presence of platelet-derived-growth factor (PDGF), they di vide and their differentiation is delayed. Triiodothyronine (T3) treat ment of progenitor cells blocks their proliferation and induces their differentiation into oligodendrocytes. T3 also induces morphological d ifferentiation of oligodendrocytes as indicated by the marked increase in the length of oligodendrocyte processes. To determine whether the effects of T3 on progenitor cell proliferation and oligodendrocyte mat uration are causally related, or instead, are independent, we examined the influence of T3 on secondary cultures of postmitotic oligodendroc ytes. We show that T3 increases morphological and functional maturatio n of postmitotic oligodendrocytes as indicated by a well developed net work of branched processes and by the expression of myelin/ oligodendr ocyte glycoprotein (MOG) and glutamine synthetase (GS). T3 increases g lutamine synthetase activity and its message level after a lag period of 24-48 h, and these levels increase through a posttranscriptional ev ent. In contrast, no effect of T3 was observed on myelin basic protein (MBP) gene expression as determined by Northern blot analysis. Our re sults indicate that thyroid hormones participate in the control of the progenitor cell proliferation and differentiation as well as in oligo dendrocyte maturation and that these two TS-regulated events are indep endent. (C) 1997 Wiley-Liss, Inc.