This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sharlin, D. S. Articles by Zoeller, R. T. Search for Related Content PubMed PubMed Citation Articles by Sharlin, D. S. Articles by Zoeller, R. T.

Polychlorinated Biphenyls Exert Selective Effects on Cellular Composition of White Matter in a Manner Inconsistent with Thyroid Hormone Insufficiency

Molecular and Cellular Biology Program (D.S.S., R.T.Z.) and Department of Biology (R.B., R.T.Z.), University of Massachusetts-Amherst, Morrill Science Center, Amherst, Massachusetts 01003

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.

Developmental exposure to polychlorinated biphenyls (PCBs) is associated with a variety of cognitive deficits in humans, and recent evidence implicates white matter development as a potential target of PCBs. Because PCBs are suspected of interfering with thyroid hormone (TH) signaling in the developing brain, and because TH is important in oligodendrocyte development, we tested the hypothesis that PCB exposure affects the development of white matter tracts by disrupting TH signaling. Pregnant Sprague Dawley rats were exposed to the PCB mixture Aroclor 1254 (5 mg/kg), with or without cotreatment of goitrogens from gestational d 7 until postnatal d 15. Treatment effects on white matter development were determined by separately measuring the cellular density and proportion of myelin-associated glycoprotein (MAG)-positive, O4-positive, and glial fibrillary acidic protein (GFAP)-positive cells in the genu of the corpus callosum (CC) and in the anterior commissure (AC). Hypothyroidism decreased the total cell density of the CC and AC as measured by 4',6-diamidino-2-phenylindole dihydrochloride (DAPI) staining and produced a disproportionate decrease in MAG-positive oligodendrocyte density with a simultaneous increase in GFAP-positive astrocyte density. These data indicate that hypothyroidism reduces cellular density of CC and AC and fosters astrocyte development at the expense of oligodendrocyte density. In contrast, PCB exposure significantly reduced total cell density but did not disproportionately alter MAG-positive oligodendrocyte density or change the ratio of MAG-positive oligodendrocytes to GFAP-positive astrocytes. Thus, PCB exposure mimicked some, but not all, of the effects of hypothyroidism on white matter composition.

This article has been cited by other articles:

				R. Bansal and R. T. Zoeller Polychlorinated Biphenyls (Aroclor 1254) Do Not Uniformly Produce Agonist Actions on Thyroid Hormone Responses in the Developing Rat Brain Endocrinology, August 1, 2008; 149(8): 4001 - 4008. [Abstract] [Full Text] [PDF]

				D. L. Fox and D. J. Good Nescient Helix-Loop-Helix 2 Interacts with Signal Transducer and Activator of Transcription 3 to Regulate Transcription of Prohormone Convertase 1/3 Mol. Endocrinol., June 1, 2008; 22(6): 1438 - 1448. [Abstract] [Full Text] [PDF]

				D. S. Sharlin, D. Tighe, M. E. Gilbert, and R. T. Zoeller The Balance between Oligodendrocyte and Astrocyte Production in Major White Matter Tracts Is Linearly Related to Serum Total Thyroxine Endocrinology, May 1, 2008; 149(5): 2527 - 2536. [Abstract] [Full Text] [PDF]

				M. Boas, U. Feldt-Rasmussen, N. E Skakkebaek, and K. M Main Environmental chemicals and thyroid function. Eur. J. Endocrinol., May 1, 2006; 154(5): 599 - 611. [Abstract] [Full Text] [PDF]