Occupational exposure to PCBs reduces striatal dopamine transporter densities only in women: A β-CIT imaging study

Seegal, Richard F.; Marek, Kenneth; Seibyl, John; Jennings, Danna; Molho, Eric; Higgins, Donald S.; Factor, Stewart A.; Fitzgerald, Edward F.; Hills, Elaine A.; Korrick, Susan A.; Wolff, Mary S.; Haase, Richard F.; Todd, Andrew C.; Parsons, Patrick J.; McCaffrey, Robert J.

doi:10.1016/j.nbd.2010.01.009

Cited by 49 publications

(29 citation statements)

References 40 publications

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“…Twenty-eight years after termination of occupational PCB exposure, an inverse relationship between DAT and PCB levels was demonstrated in human females but not in males, showing that the PCB-sensitivity of human DAT may be gender-specific (Seegal et al, 2010). The DAT, which may be importantly involved in the pathophysiology of, e.g., ADHD (Bowton et al, 2014;Mergy et al, 2014), is subject to complex trafficking and posttranslational modifications, some of which are substrate-dependent (Zahniser and Sorkin, 2009).…”

Section: Presynaptic Molecular Mechanismsmentioning

confidence: 99%

Gender-dependent and genotype-sensitive monoaminergic changes induced by polychlorinated biphenyl 153 in the rat brain

et al. 2015

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Polychlorinated biphenyls (PCBs) are present as ortho- and non-ortho-substituted PCBs, with most of the ortho-substituted congeners being neurotoxic. The present study examined effects of the ortho-substituted PCB 153 on dopamine, serotonin and amino acid neurotransmitters in the neostriatum of both male and female Wistar Kyoto (WKY) and spontaneously hypertensive rat (SHR) genotypes. PCB 153 exposure at p8, p14 and p20 had no effects on levels of these transmitters when examined at p55, but led to increased levels of both homovanillic acid and 5-hydroxyindoleacetic acid, the degradation products of dopamine and serotonin, respectively, in all groups except the female SHR. Immunoblotting showed that PCB exposure induced gender-specific decreases in dopaminergic synaptic proteins. These included a novel finding of decreased levels of the dopamine D5 receptor in both genders and genotypes, whereas male-specific changes included decreases in the postsynaptic density (PSD)-95 protein in the WKY and SHRs and a decrease in the presynaptic dopamine transporter in both the WKY and, less clearly in the male SHR. A female-specific tendency of increased vesicular monoamine transporter-2 was observed in the SHRs after PCB exposure. No changes were seen in tyrosine hydroxylase, the cytoskeletal neurotubulin or the plasma membrane marker Na(+)/K(+)-ATPase in any strain. Hence, PCB-exposure led to increases in monoamine transmitter turnover in both male and female animals, whereas decreases in both pre- and postsynaptic dopaminergic proteins were predominantly seen in male animals. PCB 153 may therefore induce neostriatal toxicity through both presynaptic and postsynaptic mechanisms in both genotypes and genders, including effects on the aspiny interneurons, which employ the D5 receptor to mediate dopamine effects on interneurons in the basal ganglia.

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Section: Presynaptic Molecular Mechanismsmentioning

confidence: 99%

Gender-dependent and genotype-sensitive monoaminergic changes induced by polychlorinated biphenyl 153 in the rat brain

et al. 2015

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“…These findings are reported in Neurobiology of Disease 38, [219][220][221][222][223][224][225]2010 and are supported by epidemiological data demonstrating increased Parkinson's disease mortality, again only in women (Steenland et al, Epidemiology 17, 8-13, 2006).…”

Section: Introductionmentioning

confidence: 60%

“…223 R.F. Seegal et al / Neurobiology of Disease 38 (2010) [219][220][221][222][223][224][225] aromatase activity in the aging male may result in the loss of a neurorisk factor (i.e., central estrogen). For this hypothesis to provide a viable explanation for the sex differences in the effects of occupational exposure to PCBs on caudate and putamen β-CIT SPECT binding, it is necessary to posit that, if we had conducted the imaging study in younger, reproductively competent workers, we would have found that men would be more affected by PCB exposure than women.…”

Section: Discussionmentioning

confidence: 99%

“…221 R.F. Seegal et al / Neurobiology of Disease 38 (2010) [219][220][221][222][223][224][225] levels and total serum lipids (expressed as gm/l). When these variables were included as potential confounders in a univariate analysis of variance, the relationship between log total lipid-adjusted serum PCBs for women was still significant (F = 5.37, p = 0.02) while the relationship between log total serum PCBs for men was not (F = 0.36, p = 0.55).…”

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confidence: 99%

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PCBs Alter Dopamine Mediated Function in Aging Workers

Seegal¹

2011

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATE (DD-MM-YYYY)2. REPORT TYPE 3. DATES COVERED (From -To) 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER E-Mail:5f. WORK UNIT NUMBER seegal@wadsworth.org PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBER SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENT ABSTRACTWe hypothesized that occupational exposure to polychlorinated biphenyls (PCBs) reduces dopamine (DA) terminal densities in the basal ganglia. We found, using -CIT imaging, a significant negative relationship between current serum PCB concentrations and the density of -CIT binding only in women. We also determined that bone lead, measured using XRF fluorescent techniques, is associated with greater decrements in memory, executive function and motor function in women compared to similarly aged men with similar bone lead levels. These latter findings are the first to demonstrate a sexual dimorphism in these behaviors associated with low to moderate bone lead concentrations. We are writing a manuscript describing changes in these behaviors with bone lead and have previously published two manuscripts describing: (i) the effects of PCB exposure on -CIT and (ii) the half lives of PCB congeners over a 28 year interval. DAMD17-02-1-0173 Final Report -April 2011 PCBs Alter Dopamine Mediated Function in Aging WorkersSeegal, Richard F.3 INTRODUCTIONAging former capacitor workers, previously employed at capacitor manufacturing facilities located approximately fifty miles north of Albany, NY underwent neuropsychological and neurological exams; completed a comprehensive occupational, residential and dietary questionnaire; had blood drawn to measure serum thyroid hormone and PCB concentrations and underwent a non-invasive test to determine bone lead concentrations in Albany, NY. Finally, approximately 40% of the subjects participated in a second...

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“…Similarly, a mixture of Aroclors caused increased striatal dopamine autoreceptor (D2) sensitivity in male but not female adult rats [98]. Importantly, effects of PCBs on striatal DAT in human populations have also been found [99]. …”

Section: Effects Of Developmental Pcb Exposure On Social Behavior Andmentioning

confidence: 99%

Endocrine-disrupting actions of PCBs on brain development and social and reproductive behaviors

Bell

2014

Current Opinion in Pharmacology

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Polychlorinated biphenyls are among the most well-studied endocrine-disrupting chemicals (EDCs) for their neurobehavioral effects, especially neurodevelopment and cognitive performance. In addition, past research has demonstrated effects of PCBs on circulating hormones and associated changes in reproductive behaviors. This article will focus on recent advances that have been made in characterizing developmental PCB effects on reproductive function, broader social and affective behaviors, and the neuroendocrine mechanisms behind such changes. In general, PCBs seem to inhibit reproductive function by suppressing multiple aspects of the associated hypothalamic circuitry. Additionally, PCBs may also reduce motivation for social behaviors and induce depressive-like symptoms via overall reductions in dopaminergic and glutamatergic functions in the limbic system. However, more work with human-relevant exposure paradigms is needed to fully support these conclusions.

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Occupational exposure to PCBs reduces striatal dopamine transporter densities only in women: A β-CIT imaging study

Cited by 49 publications

References 40 publications

Gender-dependent and genotype-sensitive monoaminergic changes induced by polychlorinated biphenyl 153 in the rat brain

Gender-dependent and genotype-sensitive monoaminergic changes induced by polychlorinated biphenyl 153 in the rat brain

PCBs Alter Dopamine Mediated Function in Aging Workers

Endocrine-disrupting actions of PCBs on brain development and social and reproductive behaviors

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