title: Developmental neurotoxicity of 3,3',4,4'-tetrachloroazobenzene with thyroxine deficit: Sensitivity of glia and dentate granule neurons in the absence of behavioral changes.
abstract: Thyroid hormones (TH) regulate biological processes implicated in neurodevelopmental disorders and can be altered with environmental exposures. Developmental exposure to the dioxin-like compound, 3,3',4,4'-tetrachloroazobenzene (TCAB), induced a dose response deficit in serum T4 levels with no change in 3,5,3'- triiodothyronine or thyroid stimulating hormone. Female Sprague-Dawley rats were orally gavaged (corn oil, 0.1, 1.0, or 10 mg TCAB/kg/day) two weeks prior to cohabitation until post-partum day 3 and male offspring from post-natal day (PND)4-21. At PND21, the high dose showed a deficit in body weight gain. Conventional neuropathology detected no neuronal death, myelin disruption, or gliosis. Astrocytes displayed thinner and less complex processes at 1.0 and 10 mg/kg/day. At 10 mg/kg/day, microglia showed less complex processes, unbiased stereology detected fewer hippocampal CA1 pyramidal neurons and dentate granule neurons (GC) and Golgi staining of the cerebellum showed diminished Purkinje cell dendritic arbor. At PND150, normal maturation of GC number and Purkinje cell branching area was not observed in the 1.0 mg/kg/day dose group with a diminished number and branching suggestive of effects initiated during developmental exposure. No effects were observed on post-weaning behavioral assessments in control, 0.1 and 1.0mg/kg/day dose groups. The demonstrated sensitivity of hippocampal neurons and glial cells to TCAB and T4 deficit raises support for considering additional anatomical features of brain development in future DNT evaluations.
authors.affiliation: Neurotoxicology Group, National Toxicology Program Laboratory, NIEHS, RTP, NC.
authors.forename: G Jean
authors.initials: GJ
authors.lastname: Harry
authors.affiliation: Division of the National Toxicology Program, NIEHS, RTP, NC.
authors.forename: Michelle J
authors.initials: MJ
authors.lastname: Hooth
authors.affiliation: Division of the National Toxicology Program, NIEHS, RTP, NC.
authors.forename: Molly
authors.initials: M
authors.lastname: Vallant
authors.affiliation: Division of the National Toxicology Program, NIEHS, RTP, NC.
authors.forename: Mamta
authors.initials: M
authors.lastname: Behl
authors.affiliation: Division of the National Toxicology Program, NIEHS, RTP, NC.
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Travlos
authors.affiliation: Howard Associates, RTP, NC.
authors.forename: James L
authors.initials: JL
authors.lastname: Howard
authors.affiliation: RTI International, RTP, NC.
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Price
authors.affiliation: Social and Scientific Systems, Inc., Durham, NC.
authors.forename: Sandra
authors.initials: S
authors.lastname: McBride
authors.affiliation: NeuroStructural Research Labs, Inc, Tampa, FL.
authors.forename: Ron
authors.initials: R
authors.lastname: Mervis
authors.affiliation: Department of Pathology & Cell Biology, University of South Florida School of Medicine, Tampa, FL ; Stereology Resource Center, Tampa, FL.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Mouton
keywords: Golgi Purkinje cells; astrocytes; dentate granule cells; developmental neurotoxicology; dioxin; glial fibrillary acidic protein; hippocampus; microglia; thyroid hormone