A single prenatal exposure to the endocrine disruptor 2,3,7,8-tetrachlorodibenzo-p-dioxin alters developmental myelination and remyelination potential in the rat brain.
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.
Fernández
M
M
BioPharmaNet-DIMORFIPA, University of Bologna, Ozzano Emilia, Bologna, Italy. mercedes.fernandez@unibo.it
Paradisi
M
M
D'Intino
G
G
Del Vecchio
G
G
Sivilia
S
S
Giardino
L
L
Calzà
L
L
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000254:growth & development* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D052244:Endocrine Disruptors / Q000008:administration & dosage* / Q000633:toxicity; D005260:Female; D006131:Growth Inhibitors / Q000008:administration & dosage* / Q000633:toxicity; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000187:drug effects* / Q000473:pathology; D009836:Oligodendroglia / Q000187:drug effects / Q000473:pathology; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage* / Q000633:toxicity; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000473:pathology; D051381:Rats
D052244:Endocrine Disruptors; D006131:Growth Inhibitors; D000072317:Polychlorinated Dibenzodioxins