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Submitted on October 18, 2007
Accepted on February 1, 2008
Program in Molecular and Cellular Biology, University Of Massachusetts, Amherst, MA; Neurotoxicology Division, NHEERL, ORD, U.S. EPA, Research Triangle Park, NC; Biology Department, University of Massachusetts, Amherst, MA
* To whom correspondence should be addressed. E-mail: tzoeller{at}bio.umass.edu.
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 (PTU). PTU induced a dose-dependent decrease in serum T4 in postnatal day 15 pups, a dose-dependent decrease in the density of MAG-positive oligodendrocytes, and an equal increase in the density of GFAP-positive astrocytes in both the corpus callosum (CC) and in the anterior commissure (AC). 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 CC was more sensitive to changes in TH than in the AC, as indicated by the slope of the regressions. Furthermore, we measured an overall reduction in the cellular density that was independent of changes in MAG and GFAP 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.
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