Neurotoxicity of Polychlorinated Biphenyls (PCBs) by Disturbance of Thyroid Hormone‐Regulated Genes

Roelens, Simon; Beck, Veronika; Aerts, Goele; Clerens, Stefan; Bergh, Gösta; Arckens, Lutgarde; Darras, Veerle; Geyten, Serge Van der

doi:10.1196/annals.1327.088

Cited by 25 publications

(12 citation statements)

References 3 publications

(4 reference statements)

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“…A broad spectrum of neurotoxicants (e.g., environmental pollutants such as metals, pesticides, and PCBs) has been shown to cause LM deficits after sub-chronic exposure (Roelens et al, 2005;Lidsky and Schneider, 2003;Ishimine et al, 2003). However, from the behavioral effects, it is difficult to deduce information about underlying mechanisms.…”

Section: Discussionmentioning

confidence: 99%

New candidate proteins for Benzo(a)pyrene-induced spatial learning and memory deficits

et al. 2011

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-Spatial learning and memory (LM) is a property of central importance in the nervous system, yet many of the molecular mechanisms for benzo(a)pyrene[B(a)P]-induced LM deficits remain enshrouded in mystery. In this study, influence of exposure to B(a)P on LM deficits in adult male SpragueDawley rats was evaluated by Morris water maze. Then morphological changes in the ultramicrostructure of hippocampal neurons were observed by transmission electron microscopy. Furthermore, to better understand the molecular changes that occur in B(a)P induced LM deficits, antibody-based protein microarrays was used to analyze protein expression changes in rats submitted to sub-chronic oral gavage of B(a)P (2 mg/kg for 90 days). Results suggested that rats in the B(a)P-treated groups have significantly impaired Morris water maze performance when compared to controls. Meanwhile, the B(a)P-induced neuronal damage was also found in the hippocampus under transmission electron microscopy. Our results demonstrate that LM deficits associated protein expression signatures could be identified from tissue proteomes, as well as potential biomarkers such as retinoic acid receptor b (RARb), synaptotagmin iosfomrs 1 (Syt1) and Brain-derived neurotrophic factor (BDNF), previously not found. This study, therefore, identifies, for the first time, multiple novel proteins that are dysregulated by B(a)P, which both enhance our understanding of B(a)P induced LM deficits and represent targets of novel therapeutics.

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Section: Discussionmentioning

confidence: 99%

New candidate proteins for Benzo(a)pyrene-induced spatial learning and memory deficits

et al. 2011

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“…Thus, as PHAHs cause a disturbance in circulating levels of thyroid hormones, it could produce a negative effect on the HPT system leading to thyroid dysfunction (48). In vitro and in vivo studies showed that exposure to PHAHs at high concentrations causes a decreased T4 concentration and a hypothyroid state (49). Exposure to congener-specific PHAHs causes a decrease in circulating thyroid hormone levels that results in an increased secretion of pituitary thyroid stimulating hormone (TSH).…”

Section: Pbdes and Thyroid Functionmentioning

confidence: 99%

Do polybrominated diphenyl ethers (PBDE) increase the risk of thyroid cancer?

Zhang

Guo

Han

et al. 2008

Bioscience Hypotheses

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An increased incidence of thyroid cancer has been reported in many parts of the world including the United States during the past several decades. Recently emerging evidence has demonstrated that polyhalogenated aromatic hydrocarbons (PHAHs), particularly polybrominated diphenyl ethers (PBDEs), alter thyroid hormone homeostasis and cause thyroid dysfunction. However, few studies have been conducted to test whether exposure to PBDEs and other PHAHs increases the risk of thyroid cancer. Here, we hypothesize that elevated exposure to PHAHs, particularly PBDEs, increases the risk of thyroid cancer and may explain part of the increase in incidence of thyroid cancer during the past several decades. In addition, genetic and epigenetic variations in metabolic pathway genes may alter the expression and function of metabolic enzymes which are involved in the metabolism of endogenous thyroid hormones and the detoxification of PBDEs and other PHAHs. Such variation may result in different individual susceptibilities to PBDEs and other PHAHs and the subsequent development of thyroid cancer. The investigation of this hypothesis will lead to an improved understanding of the role of PBDEs and other PHAHs in thyroid tumorigenesis and may provide a real means to prevent this deadly disease.

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“…Increased gene expression in the fetal rat brain after maternal exposure to PCBs included neuroendocrine-specific protein A, neurogranin, myelin basic protein, and the transcription factors oct-1 and hairy enhancer of split (132)(133)(134), RC3/neurogranin and myelin basic protein in pups of PCB-treated dams (134). In a study of brain protein extracts from PCB-treated chicken embryos 17 of 109 differentially expressed proteins differed with PCB treatment (135). Malic enzyme (ME) gene expression is regulated mainly by THs and was increased by exposure to HCB, probably through still unidentified nuclear proteins that bind to the TRE of the ME promoter (136).…”

Section: Mechanisms Of Actionmentioning

confidence: 99%

Environmental chemicals and thyroid function

Boas¹,

Feldt‐Rasmussen

Skakkebæk³

et al. 2006

eur j endocrinol

457

290

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There is growing evidence that environmental chemicals can disrupt endocrine systems. Most evidence originates from studies on reproductive organs. However, there is also suspicion that thyroid homeostasis may be disrupted. Several groups of chemicals have potential for thyroid disruption. There is substantial evidence that polychlorinated biphenyls, dioxins and furans cause hypothyroidism in exposed animals and that environmentally occurring doses affect human thyroid homeostasis. Similarly, flame retardants reduce peripheral thyroid hormone (TH) levels in rodents, but human studies are scarce. Studies also indicate thyroid-disruptive properties of phthalates, but the effect of certain phthalates seems to be stimulative on TH production, contrary to most other groups of chemicals. Thyroid disruption may be caused by a variety of mechanisms, as different chemicals interfere with the hypothalamic -pituitary -thyroid axis at different levels. Mechanisms of action may involve the sodium-iodide symporter, thyroid peroxidase enzyme, receptors for THs or TSH, transport proteins or cellular uptake mechanisms. The peripheral metabolism of the THs can be affected through effects on iodothyronine deiodinases or hepatic enzymes. Even small changes in thyroid homeostasis may adversely affect human health, and especially fetal neurological development may be vulnerable. It is therefore urgent to clarify whether the animal data showing effects of chemicals on thyroid function can be extended to humans. European Journal of Endocrinology 154 599-611

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Neurotoxicity of Polychlorinated Biphenyls (PCBs) by Disturbance of Thyroid Hormone‐Regulated Genes

Cited by 25 publications

References 3 publications

New candidate proteins for Benzo(a)pyrene-induced spatial learning and memory deficits

New candidate proteins for Benzo(a)pyrene-induced spatial learning and memory deficits

Do polybrominated diphenyl ethers (PBDE) increase the risk of thyroid cancer?

Environmental chemicals and thyroid function

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