Developmental Neurotoxicity of 3,3',4,4'-Tetrachloroazobenzene with Thyroxine Deficit: Sensitivity of Glia and Dentate Granule Neurons in the Absence of Behavioral Changes
1
Neurotoxicology Group, National Toxicology Program Laboratory, National Institute of Environmental Health Science (NIEHS), Research Triangle Park (RTP), NC 27709, USA
2
Division of the National Toxicology Program, NIEHS, Research Triangle Park (RTP), NC 27709, USA
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Howard Associates, Research Triangle Park (RTP), NC 27709, USA
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RTI International, Research Triangle Park (RTP), NC 27709, USA
5
Social and Scientific Systems, Incorporated, Durham, NC 27709, USA
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NeuroStructural Research Labs, Incorporated, Tampa, FL 33613, USA
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Department of Pathology & Cell Biology, University of South Florida School of Medicine, Tampa, FL 33613, USA
8
Stereology Resource Center, Tampa, FL 33741, USA
*
Author to whom correspondence should be addressed.
Toxics 2014, 2(3), 496-532; https://doi.org/10.3390/toxics2030496
Received: 1 August 2014 / Revised: 2 September 2014 / Accepted: 4 September 2014 / Published: 24 September 2014
(This article belongs to the Special Issue Developmental Neurotoxicology)
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 1.0 mg/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. View Full-TextKeywords:
astrocytes; thyroid hormone; developmental neurotoxicology; microglia; Golgi Purkinje cells; dentate granule cells; dioxin; hippocampus; glial fibrillary acidic protein
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Harry, G.J.; Hooth, M.J.; Vallant, M.; Behl, M.; Travlos, G.S.; Howard, J.L.; Price, C.J.; McBride, S.; Mervis, R.; Mouton, P.R. Developmental Neurotoxicity of 3,3',4,4'-Tetrachloroazobenzene with Thyroxine Deficit: Sensitivity of Glia and Dentate Granule Neurons in the Absence of Behavioral Changes. Toxics 2014, 2, 496-532.