Blocking Brain Development: How PCBs Disrupt Thyroid Hormone

Abstract

Vol. 113, No. 7 EnvironewsOpen AccessBlocking Brain Development: How PCBs Disrupt Thyroid Hormoneis accompanied byPolychlorinated Biphenyls Disturb Differentiation of Normal Human Neural Progenitor Cells: Clue for Involvement of Thyroid Hormone Receptors Valerie J. Brown Valerie J. Brown Search for more papers by this author Published:1 July 2005https://doi.org/10.1289/ehp.113-a472bAboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit Polychlorinated biphenyls (PCBs) have long been known to alter growth and development in animals and humans, and are suspected of interfering with the action of thyroid hormone (TH) in humans. Much less is known about which congeners of this large chemical family may have such action and how they interfere with TH. Now, in an in vitro study using human brain stem cells, a team of German and Californian researchers shows how a specific PCB congener, PCB-118, can interrupt normal TH function and cause the premature differentiation of one type of brain cell [EHP 113:871–876].Many animal studies, primarily in rats, suggest that PCBs can profoundly affect fetal brain development, which itself is highly dependent on the availability and amount of TH, principally from the mother. PCBs are known to lower circulating blood levels of TH by increasing TH metabolism and binding to TH transport proteins; the exact mechanisms and effects of TH disruption by PCBs are unclear, however. Some epidemiologic evidence suggests a link between PCB exposure during fetal development and subsequent cognitive problems in children, such as lowered overall IQ, attention and motor deficits, and impaired impulse control. The suspicion that these problems may be related to PCBs’ effects on the timing and type of brain cell differentiation led to the current study.Stem cells known as normal human neural progenitor (NHNP) cells develop into three types of brain cells: neurons, which receive and transmit electrical signals via axons and synapses; astrocytes, which manage neurons’ surrounding environment; and oligodendrocytes, which produce myelin, the fatty sheath that insulates axons. TH is known to control the timing of oligodendrocyte differentiation.The research team exposed NHNP cells to two PCB congeners—PCB-118 and PCB-126—and observed the effects on cell differentiation. They found that cells exposed to PCB-118 prematurely turned into oligodendrocytes. This finding suggests strongly that PCBs may facilitate the binding of coactivator proteins to cellular TH receptors; these proteins then mimic the action of TH. Paradoxically, a surplus of oligodendrocytes early in brain development may lead to a dearth later, because if there are proportionally fewer neurons, many oligodendrocytes cannot wrap an axon or reproduce. In that case, they undergo apoptosis, or programmed cell death. The end result would likely be a drop in the total number of brain cells.The current study is consistent with an earlier rat study published in the April 2004 issue of EHP, which found that PCBs interfered directly with fetal TH receptor signaling, as opposed to reducing circulating maternal TH levels. Like many other studies, that study used Aroclor 1254, a commercial mixture of several PCB congeners, and did not determine the effects of each congener. The current study compared two PCB congeners that differ somewhat in their toxic equivalence (TEQ). The results showed that the lower-TEQ congener (PCB-118) acted via the TH pathway while the higher-TEQ congener (PCB-126) did not. The apparent toxicity of a PCB congener with a low TEQ also suggests that the TEQ system may not be a reliable measure of all types of toxicity.FiguresReferencesRelatedDetailsRelated articlesPolychlorinated Biphenyls Disturb Differentiation of Normal Human Neural Progenitor Cells: Clue for Involvement of Thyroid Hormone Receptors18 April 2005Environmental Health Perspectives Vol. 113, No. 7 July 2005Metrics About Article Metrics Publication History Originally published1 July 2005Published in print1 July 2005 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.