Effects ofin Uteroand Lactational Exposure of the Laboratory Rat to 2,4,2′,4′- and 3,4,3′,4′-Tetrachlorobiphenyl on Dopamine Function

Seegal, Richard F.; Brosch, Karl O.; Okoniewski, Richard

doi:10.1006/taap.1997.8226

Cited by 119 publications

(72 citation statements)

References 51 publications

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“…Animals were exposed on a daily basis to either Aroclor 1254 (PCB-exposed) or corn oil (control) for 3 days or 1, 2, or 8 weeks. We have used this procedure in the past (Seegal et al 1997) and have found that it is a nonstressful means of providing a known quantity of PCBs to the animal. This procedure was used for all animals, including those that underwent microdialysis and those sacrificed for determination of postmortem striatal tissue DA concentrations.…”

Section: Methodsmentioning

confidence: 99%

“…Polychlorinated biphenyls (PCBs) are widespread, persistent environmental toxicants that have been associated, particularly during development, with behavioral deficits in both humans and experimental animals (Jacobson and Jacobson 1996;Patandin et al 1999;Roegge et al 2000;Stewart et al 2000) and with changes in biochemical and neurochemical function (Eriksson 1998;Goldey et al 1995;Seegal et al 1997).…”

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confidence: 99%

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Polychlorinated biphenyls alter extraneuronal but not tissue dopamine concentrations in adult rat striatum: an in vivo microdialysis study.

Seegal

Okoniewski

Brosch

et al. 2002

Environ Health Perspect

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Polychlorinated biphenyls (PCBs) reduce tissue dopamine (DA) concentrations and increase media DA concentrations in both in vitro preparations of bovine adrenal chromaffin cells and adult rat striatal tissue. To determine whether these changes also occur in the intact animal, we used in vivo microdialysis to determine changes in concentrations of DA in striatal dialysates from freely moving adult male rats after exposure to 25 mg/kg/day Aroclor 1254 for varying periods of time. We also determined DA concentrations in striatal tissue obtained postmortem from similarly treated animals. The effects of PCBs on dialysate DA concentrations depended on the length of exposure; DA concentrations were significantly elevated after 3 days of exposure and were significantly reduced after exposure for periods of 1 week or longer. On the other hand, striatal tissue concentrations of DA, determined postmortem in rats exposed to PCBs for the same periods of time, were not significantly altered. We suggest that these time-dependent alterations in dialysate DA concentrations a) reflect PCB-induced alterations of both plasma membrane and vesicular DA transporter function; b) provide a more sensitive index of altered central DA function after exposure to PCBs than does measurement of postmortem tissue DA concentrations; and c) play an important role in mediating some PCB-mediated changes in behavior.

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Polychlorinated biphenyls alter extraneuronal but not tissue dopamine concentrations in adult rat striatum: an in vivo microdialysis study.

Seegal

Okoniewski

Brosch

et al. 2002

Environ Health Perspect

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“…Results from in vivo rat studies have shown that adult PCB exposure alters extra-neuronal DA concentrations (Seegal et al, 2002), and eventually reduces the levels of frontal cortical and striatal DA (Seegal et al, 1997). Other studies, in both adult non-human primates and rats exposed to PCBs for several weeks, revealed a reduction in the number of tyrosine hydroxylase positive (TH + ) DA neurons in the substantia nigra (SN) (Seegal, Chishti, and Brosch, unpublished observations).…”

Section: Introductionmentioning

confidence: 97%

Polychlorinated biphenyl-induced oxidative stress in organotypic co-cultures: Experimental dopamine depletion prevents reductions in GABA

Lyng

Seegal

2008

NeuroToxicology

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Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants that have been demonstrated to be toxic to the dopamine (DA) systems of the central nervous system. One proposed mechanism for PCB-induced DA neurotoxicity is inhibition of the vesicular monoamine transporter (VMAT); such inhibition results in increased levels of unsequestered DA and DA metabolism leading to oxidative stress. We have used an organotypic co-culture system of developing rat striatum and ventral mesencephalon (VM) to determine whether alterations in the vesicular storage of DA, resulting from PCB exposure and consequent induction of oxidative stress, leads to GABA and DA neuronal dysfunction. 24 hr exposure to an environmentally relevant mixture of PCBs reduced tissue DA and GABA concentrations, increased medium levels of DA and measures of oxidative stress in both the striatum and VM. Alterations in neurochemistry and increases in measures of oxidative stress were blocked in the presence of n-acetylcysteine (NAC). Although NAC treatment did not alter PCB-induced changes in DA neurochemistry, it did protect against reductions in GABA concentration. To determine whether alterations in the vesicular storage of DA were responsible for PCB-induced oxidative stress and consequent reductions in GABA levels, we depleted DA from the co-cultures using α-methyl-p-tyrosine (AMPT). AMPT reduced striatal and VM DA levels by 90% and 70%, respectively. PCB exposure, following DA depletion, neither increased levels of oxidative stress nor resulted in GABA depletion. These results suggest that PCB-induced alterations in the vesicular storage of DA, resulting in increased levels of unsequestered DA, leads to increased oxidative stress, depletion of tissue glutathione, and consequent reductions in tissue GABA concentrations.

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“…There is a lack of sufficient knowledge of the biologic mechanism for the observed effect of PCBs and organocholrine pesticides on ADHD and attention in humans [25]. PCBs can dis rupt dopaminergic functions, as reflected in alterations in dopamine levels in the cell culture and in the brains of laboratory animals [26,27]; this is one possible mechanism whereby PCBs may affect attention-related behaviors, since decreases in cellular dopamine have been correlated with attention disorders such as ADHD [28]. A number of epidemiological studies, which assess the neuropsychological consequences of exposure to PCBs, have been performed over the last 11 years [29][30][31][32][33][34][35] ( Table 2).…”

Section: Criteria Of the Selection Of Studies To The Reviewmentioning

confidence: 99%

Review of current evidence on the impact of pesticides, polychlorinated biphenyls and selected metals on attention deficit / hyperactivity disorder in children

Polańska¹,

Jurewicz²,

Hanke³

2013

International Journal of Occupational Medicine and Environmental Health

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The aim of this review was to investigate the association between attention deficit / hyperactivity disorder (ADHD) or AD HD-related symptoms and industrial chemicals, such as organophosphates and organochlorine pesticides, polychlorinated biphenyls (PCBs), lead, mercury and manganese. Medline, PubMed and EBSCO searches were performed to identify the studies that analyzed the association of prenatal and postnatal child exposure to such toxicants and ADHD or ADHD-re lated symptoms. The review is restricted to human studies published in English in peer-reviewed journals since 2000. Most of the presented studies focused on pesticides, PCB and lead. The impact of mercury and manganese was investigated less frequently. The findings indicate that children's exposure to organophosphate pesticides may cause symptoms consistent with pervasive developmental disorder, ADHD or attention problems. Exposures to organochlorine pesticides and PCBs were associated with ADHD-like behaviors such as alertness, quality of alert response, and cost of attention. The studies provided evidence that blood lead level below 10 μg/dl was associated with ADHD or ADHD-related symptoms. Informa tion on the association between exposure to mercury and neurotoxicity is limited, and requires further confirmation in future research. Two studies indicated that exposure to manganese is related to ADHD; such exposure and its impact on children neurodevelopment need to be further investigated. Future studies should use a prospective design with multiple biological samples collected over time for better assessment of exposure and its critical windows. Additionally, inclusion of potential confounding factors and co-exposures is crucial.

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Effects ofin Uteroand Lactational Exposure of the Laboratory Rat to 2,4,2′,4′- and 3,4,3′,4′-Tetrachlorobiphenyl on Dopamine Function

Cited by 119 publications

References 51 publications

Polychlorinated biphenyls alter extraneuronal but not tissue dopamine concentrations in adult rat striatum: an in vivo microdialysis study.

Polychlorinated biphenyls alter extraneuronal but not tissue dopamine concentrations in adult rat striatum: an in vivo microdialysis study.

Polychlorinated biphenyl-induced oxidative stress in organotypic co-cultures: Experimental dopamine depletion prevents reductions in GABA

Review of current evidence on the impact of pesticides, polychlorinated biphenyls and selected metals on attention deficit / hyperactivity disorder in children

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