single prenatal exposure to the endocrine disruptor 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin alters developmental myelination and remyelination potential in the rat brain

J. Neurochem. (2010) 115, 897-909. ABSTRACT: Polychlorinated dibenzo‐dioxins, furans and dioxin‐like polychlorinated biphenyls are ubiquitous in foodstuffs of animal origin and accumulate in the fatty tissues of animals and humans. The most toxic congener is 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD...

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Published in:	Journal of neurochemistry 2010-11, Vol.115 (4), p.897-909
Main Authors:	Fernández, M, Paradisi, M, D'Intino, G, Del Vecchio, G, Sivilia, S, Giardino, L, Calzà, L
Format:	Article
Language:	eng
Subjects:	2,3,7,8‐tetrachlorodibenzo‐p‐dioxin Adipose tissue Animals Animals, Newborn Biochemistry and metabolism Biological and medical sciences Biomarkers Brain Brain - drug effects Brain - growth & development Brain - pathology Cell Proliferation - drug effects Cells, Cultured Central nervous system Cerebellum Congeners Dams Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Developmental biology Diencephalon Dioxins Endocrine disruptors Endocrine Disruptors - administration & dosage Endocrine Disruptors - toxicity Female Food Fundamental and applied biological sciences. Psychology Furans Gene expression Growth Inhibitors - administration & dosage Growth Inhibitors - toxicity Lipophilic Male Medical sciences Medulla oblongata Metabolism Milk Myelin basic protein Myelination Nerve Fibers, Myelinated - drug effects Nerve Fibers, Myelinated - pathology neural stem cells Neurochemistry Neurology neurospheres oligodendrocyte precursor cells Oligodendrocytes Oligodendroglia - drug effects Oligodendroglia - pathology PCB Placenta Platelet-derived growth factor polychlorinated biphenyls Polychlorinated Dibenzodioxins - administration & dosage Polychlorinated Dibenzodioxins - toxicity Pregnancy Prenatal care Prenatal experience Prenatal Exposure Delayed Effects - chemically induced Prenatal Exposure Delayed Effects - pathology Progeny Rats TCDD Thyroid hormones Vertebrates: nervous system and sense organs
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Summary:	J. Neurochem. (2010) 115, 897-909. ABSTRACT: Polychlorinated dibenzo‐dioxins, furans and dioxin‐like polychlorinated biphenyls are ubiquitous in foodstuffs of animal origin and accumulate in the fatty tissues of animals and humans. The most toxic congener is 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD), a lipophilic endocrine‐disrupting molecule that accumulates in adipose tissue, placenta and milk. polychlorinated biphenyls and TCDD are known to interfere with thyroid hormone metabolism and signaling in the developing brain. As thyroid hormone is critical in the myelination process during development, we investigated the effect of a single dose of TCDD prenatal exposure (gestational day 18) on the myelination process. A semi‐quantitative analysis of oligodendrocyte markers at different stages of maturation was performed in the offspring's medulla oblongata, cerebellum, diencephalon and telenchephalon at different postnatal days (2/3, 14, 30 and 135). The most significant alterations observed were: (i) cerebellum and medulla oblongata: altered expression of oligodendroglial lineage and platelet‐derived growth factor alpha receptor, myelin basic protein (MBP) mRNAs (P2/3, P135) and MBP protein (P135); (ii) diencephalon: increase in platelet‐ derived growth factor alpha receptor mRNA level (P2/3); (iii) telenchephalon: decrease in MBP mRNA expression. The oligodendroglial generation capability of adult neural stem/precursor cells obtained ex vivo from TCDD and vehicle‐treated dams was then explored. TCDD impairs neurosphere proliferation and retards CNPase‐positive cell generation from adult neurospheres.
ISSN:	0022-3042 1471-4159