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

Seegal, Richard F.; Okoniewski, Richard; Brosch, Karl O.; Bemis, Jeffrey C.

doi:10.1289/ehp.021101113

Cited by 74 publications

(48 citation statements)

References 35 publications

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“…The mechanisms of PCB neurotoxicity most likely involve multiple modes of action, which largely depend upon the congener structure. The mechanisms include effects on thyroid hormone dependent neurodevelopment (Zoeller et al, 2002); binding to and activation of the aryl hydrocarbon receptor (AhR) by planar PCBs by a mechanism similar to that of dioxin (Collins et al, 2008;Powers et al, 2005); impairment of the function of glutamate-nitric oxide-cGMP pathway (Piedrafita et al, 14 2008); effects on brain cholinergic muscarinic receptors (Coccini et al, 2006); and damage to dopaminergic neurons (Seegal et al, 2002). In our study, CB-153 (a PCB congener with a non-planar structure) was the most abundant PCB congener in CSF and cerebellum GM.…”

Section: Pcb and Pcb Metabolitesmentioning

confidence: 99%

Organohalogen contaminants and metabolites in cerebrospinal fluid and cerebellum gray matter in short-beaked common dolphins and Atlantic white-sided dolphins from the western North Atlantic

Montie

Reddy

Gebbink

et al. 2009

Environmental Pollution

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Section: Pcb and Pcb Metabolitesmentioning

confidence: 99%

Organohalogen contaminants and metabolites in cerebrospinal fluid and cerebellum gray matter in short-beaked common dolphins and Atlantic white-sided dolphins from the western North Atlantic

Montie

Reddy

Gebbink

et al. 2009

Environmental Pollution

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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number of tyrosine hydroxylase positive (TH + ) DA neurons in the substantia nigra (SN) (Seegal, Chishti, and Brosch, unpublished observations).…”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: 98%

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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“…Previously, PCBs and their metabolites were shown to impact neurotransmitter and steroid hormone systems underlying reproductive function (Khan and Thomas, 2001;Ptak et al, 2005;Seegal et al, 1985;Seegal et al, 2002;Tsai et al, 1997). These changes in turn are likely to have profound effects on reproductive behaviors.…”

Section: Introductionmentioning

confidence: 99%

The effects of prenatal PCBs on adult female paced mating reproductive behaviors in rats

Steinberg

Juenger

Gore

2007

Hormones and Behavior

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Polychlorinated biphenyls (PCBs) are a family of toxicants that persist in measurable quantities in human and wildlife tissues, despite their ban in production in 1977. Some PCB mixtures can act as endocrine disrupting chemicals (EDCs) by mimicking or antagonizing the actions of hormones in the brain and periphery. When exposure to hormonally active substances such as PCBs occurs during vulnerable developmental periods, particularly prenatally or in early postnatal life, they can disrupt sex-specific patterning of the brain, inducing permanent changes that can later be manifested as improper sexual behaviors. Here, we investigated the effects of prenatal exposure to the PCB mixture Aroclor (A) 1221 on adult female reproductive behaviors in a dose-response model in the SpragueDawley rat. Using a paced mating paradigm that permits the female to set the timing of mating and control contact with the male during copulation, we were able to uncover significant differences in female-typical sexual activities in A1221-exposed females. Specifically, A1221 causes significant effects on mating trial pacing, vocalizations, ambulation and the female's likelihood to mate. The results further demonstrate that the intermediate treatment group has the greatest number of disrupted endpoints, suggestive of non-linear dose responses to A1221. These data demonstrate that the behavioral phenotype in adulthood is disrupted by low, ecologically relevant exposures to PCBs, and the results have implications for reproductive success and health in wildlife and women. KeywordsAroclor 1221; Paced mating; PCB; Female reproductive behavior; Endocrine disruption Polychlorinated biphenyls (PCBs) were used in industry as inflammable coolants and lubricants and as components of paints and plastics. Banned in 1977 in response to dawning public awareness of their estrogenic and potentially toxic effects on humans and wildlife, PCBs continue to leach into soil, air and groundwater via retired industrial equipment, and from old factories and buildings. PCBs may have variable degrees of impact depending on which congeners or congener mixtures are involved, the organism's age at exposure, the sex of the individual, the degree of exposure and the availability of compensatory diet or social buffering to counteract those effects. An accurate evaluation of ecologically relevant xenobiotic exposure (Battershill, 1994;Brouwer et al., 1999).The neuroendocrine system serves as an interface between the central nervous system and peripheral endocrine organs, and thus represents a prime target for endocrine disruption by PCBs (Patisaul et al., 2006). PCBs and their metabolites can act at multiple nodes of the neuroendocrine axis: they may serve as hormone mimics (Connor et al., 1997), alter circulating hormone levels (Desaulniers et al., 1999), change patterns of estrous cyclicity (Meerts et al., 2004;Buitenhuis et al., 2004), disrupt hormone metabolism Kester et al., 2000;Yamane et al., 1975), influence endocrine-related and hypothalamic gene expression ...

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

Cited by 74 publications

References 35 publications

Organohalogen contaminants and metabolites in cerebrospinal fluid and cerebellum gray matter in short-beaked common dolphins and Atlantic white-sided dolphins from the western North Atlantic

Organohalogen contaminants and metabolites in cerebrospinal fluid and cerebellum gray matter in short-beaked common dolphins and Atlantic white-sided dolphins from the western North Atlantic

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

The effects of prenatal PCBs on adult female paced mating reproductive behaviors in rats

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