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The Balance between Oligodendrocyte and Astrocyte Production in Major White Matter Tracts Is Linearly Related to Serum Total Thyroxine

Program in Molecular and Cellular Biology (D.S.S., D.T., R.T.Z.) and Department of Biology (R.T.Z.), University of Massachusetts, Amherst, Massachusetts 01003; and Division of Neurotoxicology (M.E.G.), NHEERL, ORD, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711

Address all correspondence and requests for reprints to: R. Thomas Zoeller, Biology Department, Morrill Science Center, University of Massachusetts-Amherst, Amherst, Massachusetts 01003. E-mail: tzoeller{at}bio.umass.edu (http://www.bio.umass.edu/biology/zoeller).

Thyroid hormone (TH) may control the ratio of oligodendrocytes to astrocytes in white matter by acting on a common precursor of these two cell types. If so, then TH should produce an equal but opposite effect on the density of these two cells types across all TH levels. To test this, we induced graded TH insufficiency by treating pregnant rats with increasing doses of propylthiouracil. Propylthiouracil induced a dose-dependent decrease in serum T₄ in postnatal d 15 pups, a dose-dependent decrease in the density of MAG-positive oligodendrocytes, and an equal increase in the density of glial fibrillary acidic protein-positive astrocytes in both the corpus callosum and anterior commissure. Linear regression analyses demonstrated a strong correlation between glial densities and serum T₄; this correlation was positive for astrocytes and negative for oligodendrocytes. Surprisingly, oligodendrocyte density in the corpus callosum was more sensitive to changes in TH than in the anterior commissure, as indicated by the slope of the regressions. Furthermore, we measured an overall reduction in the cellular density that was independent of changes in myelin-associated glycoprotein and glial fibrillary acidic protein-positive cells. These data strongly support the interpretation that TH controls the balance of production of oligodendrocytes and astrocytes in major white matter tracts of the developing brain by acting on a common precursor of these cell types. Moreover, these findings indicate that major white matter tracts may differ in their sensitivity to TH insufficiency.