title: Polychlorinated biphenyls exert selective effects on cellular composition of white matter in a manner inconsistent with thyroid hormone insufficiency.
abstract: 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.
authors.affiliation: Molecular and Cellular Biology Program, University of Massachusetts-Amherst, Morrill Science Center, 01003, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Sharlin
authors.forename: Ruby
authors.initials: R
authors.lastname: Bansal
authors.forename: R Thomas
authors.initials: RT
authors.lastname: Zoeller
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D013956:Antithyroid Agents; D020111:Chlorodiphenyl (54% Chlorine); D003337:Corpus Callosum / Q000166:cytology / Q000187:drug effects* / Q000196:embryology* / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D007037:Hypothyroidism / Q000139:chemically induced / Q000196:embryology* / Q000378:metabolism; D009186:Myelin Sheath / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018992:Myelin-Associated Glycoprotein / Q000187:drug effects / Q000378:metabolism; D009413:Nerve Fibers, Myelinated / Q000187:drug effects* / Q000378:metabolism; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012686:Septal Nuclei / Q000166:cytology / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D013963:Thyroid Hormones / Q000172:deficiency / Q000378:metabolism
chemical_list: D013956:Antithyroid Agents; D004785:Environmental Pollutants; D018992:Myelin-Associated Glycoprotein; D013963:Thyroid Hormones; D020111:Chlorodiphenyl (54% Chlorine); D011078:Polychlorinated Biphenyls