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

Abstract

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.

Actions of endocrine-disrupting chemicals on stem/progenitor cells during development and disease

“…Exposure to TCDD inhibited oligodendroglial lineage potential, resulting in a lower percentage of glial fibrillary acid protein-positive cells (Fernandez et al 2010). Furthermore, oligodendroglial maturation was inhibited as indicated by a decrease in CNPase-positive oligodendrocytes (Fernandez et al 2010).…”

“…Exposure to TCDD inhibited oligodendroglial lineage potential, resulting in a lower percentage of glial fibrillary acid protein-positive cells (Fernandez et al 2010). Furthermore, oligodendroglial maturation was inhibited as indicated by a decrease in CNPase-positive oligodendrocytes (Fernandez et al 2010). Exposure to the FR BDE-209 compromised adult NSC differentiation by inhibiting neurite outgrowth and neuron differentiation, but promoting glial cell differentiation (Zhang et al 2010).…”

The protective action of tocopherol and acetylsalicylic acid on the behavior of rats treated with dioxins

“…[2][3][4][5][6] Dioxin and related compounds are the cause of neurological disorders in humans and experimental animals as well as their offspring in the perinatal period after exposure to these compounds through the placenta and milk in prenatal and postnatal periods. [7][8][9] Dioxins significantly affect brain development in the prenatal and postnatal periods associated with the time of breastfeeding by mothers intoxicated with dioxins. [10][11][12][13] Changes caused by dioxins in the central nervous system (CNS) in pre-and postnatal periods lead to later changes in life.…”

“…Functional disorders of the brain structures, including the cerebellum and diencephalon, should also be associated with changes in thyroid hormone levels and estrogen receptors (ER) induced by dioxins. 9,[14][15][16][17] It was shown that dioxins lead to the underdevelopment of the bones and teeth in both humans and animals as a result of mineralization disorders. [18][19][20] It was found that after birth there is a significant concentration of dioxins in the breast milk, correlating negatively with a newborn head circumference.…”

Avaliação do desenvolvimento do sistema nervoso central de camundongos Balb/c expostos à fumaça do cigarro no início do período pós-natal

“…As primeiras células precursoras de oligodendrócitos, responsáveis pela produção da mielina no SNC, aparecem por volta da nona semana em humanos e são caracterizadas pela expressão de Olig 1, receptor alfa do fator de crescimento derivados de plaquetas (PDGFαR) e de NG2. A maturação dos oligodendrócitos é marcada pela expressão da proteína básica de mielina (PBM) e da proteína proteolipídeo (PLP) (FERNÁNDEZ et al, 2010). Em roedores, no primeiro dia de vida pós-natal os oligodendrócitos maduros já expressam marcadores como a PBM na medula espinhal (DORETTO et al, 2011).…”