The developmental neurotoxicity of legacy vs. contemporary polychlorinated biphenyls (PCBs): similarities and differences

  • Carolyn Klocke
  • Sunjay Sethi
  • Pamela J. LeinEmail author
Fifty Years of PCB Research: New Approaches and Discoveries and still so much more to learn


Although banned from production for decades, PCBs remain a significant risk to human health. A primary target of concern is the developing brain. Epidemiological studies link PCB exposures in utero or during infancy to increased risk of neuropsychiatric deficits in children. Nonclinical studies of legacy congeners found in PCB mixtures synthesized prior to the ban on PCB production suggest that non-dioxin-like (NDL) congeners are predominantly responsible for the developmental neurotoxicity associated with PCB exposures. Mechanistic studies suggest that NDL PCBs alter neurodevelopment via ryanodine receptor-dependent effects on dendritic arborization. Lightly chlorinated congeners, which were not present in the industrial mixtures synthesized prior to the ban on PCB production, have emerged as contemporary environmental contaminants, but there is a paucity of data regarding their potential developmental neurotoxicity. PCB 11, a prevalent contemporary congener, is found in the serum of children and their mothers, as well as in the serum of pregnant women at increased risk for having a child diagnosed with a neurodevelopmental disorder (NDD). Recent data demonstrates that PCB 11 modulates neuronal morphogenesis via mechanisms that are convergent with and divergent from those implicated in the developmental neurotoxicity of legacy NDL PCBs. This review summarizes these data and discusses their relevance to adverse neurodevelopmental outcomes in humans.


Axonal outgrowth Calcium signaling CREB Dendritic arborization Neuronal morphogenesis Neurodevelopmental disorders Persistent organic pollutants Ryanodine receptor 


Funding information

This work was supported by the United States National Institute of Environmental Health (grant numbers R01 ES014901, R01 ES014901-09S1 (ViCTER supplement), P30 ES023513, T32 ES007059).

Compliance with ethical standards

Conflict of interest

The authors have no conflicts of interest to disclose.


The sponsors were not involved in the writing of the paper or in the decision to submit the work for publication.


  1. Alaerts K, Swinnen SP, Wenderoth N (2016) Sex differences in autism: a resting-state fMRI investigation of functional brain connectivity in males and females. Soc Cogn Affect Neurosci 11:1002–1016. CrossRefGoogle Scholar
  2. Ampleman MD, Martinez A, DeWall J, Rawn DF, Hornbuckle KC, Thorne PS (2015) Inhalation and dietary exposure to PCBs in urban and rural cohorts via congener-specific measurements. Environ Sci Technol 49:1156–1164. CrossRefGoogle Scholar
  3. Antunes Fernandes EC, Hendriks HS, van Kleef RG, Reniers A, Andersson PL, van den Berg M, Westerink RH (2010a) Activation and potentiation of human GABAA receptors by non-dioxin-like PCBs depends on chlorination pattern. Toxicol Sci 118:183–190. CrossRefGoogle Scholar
  4. Antunes Fernandes EC, Hendriks HS, van Kleef RG, van den Berg M, Westerink RH (2010b) Potentiation of the human GABA(A) receptor as a novel mode of action of lower-chlorinated non-dioxin-like PCBs. Environ Sci Technol 44:2864–2869. CrossRefGoogle Scholar
  5. Bansal R, You SH, Herzig CT, Zoeller RT (2005) Maternal thyroid hormone increases HES expression in the fetal rat brain: an effect mimicked by exposure to a mixture of polychlorinated biphenyls (PCBs). Brain Res Dev Brain Res 156:13–22. CrossRefGoogle Scholar
  6. Berger-Sweeney J, Hohmann CF (1997) Behavioral consequences of abnormal cortical development: insights into developmental disabilities. Behav Brain Res 86:121–142CrossRefGoogle Scholar
  7. Berghuis SA, Bos AF, Sauer PJ, Roze E (2015) Developmental neurotoxicity of persistent organic pollutants: an update on childhood outcome. Arch Toxicol 89:687–709. CrossRefGoogle Scholar
  8. Bernhoft A, Nafstad I, Engen P, Skaare JU (1994) Effects of pre- and postnatal exposure to 3,3′,4,4′,5-pentachlorobiphenyl on physical development, neurobehavior and xenobiotic metabolizing enzymes in rats. Environ Toxicol Chem 13:1589–1597. CrossRefGoogle Scholar
  9. Berridge MJ (2006) Calcium microdomains: organization and function. Cell Calcium 40:405–412. CrossRefGoogle Scholar
  10. Boix J, Cauli O, Felipo V (2010) Developmental exposure to polychlorinated biphenyls 52, 138 or 180 affects differentially learning or motor coordination in adult rats. Mechanisms involved. Neuroscience 167:994–1003. CrossRefGoogle Scholar
  11. Brini M, Cali T, Ottolini D, Carafoli E (2014) Neuronal calcium signaling: function and dysfunction. Cell Mol Life Sci 71:2787–2814. CrossRefGoogle Scholar
  12. Bu Q et al (2017) CREB signaling is involved in rett syndrome pathogenesis. J Neurosci 37:3671–3685. CrossRefGoogle Scholar
  13. Bushnell PJ, Rice DC (1999) Behavioral assessments of learning and attention in rats exposed perinatally to 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126). Neurotoxicol Teratol 21:381–392CrossRefGoogle Scholar
  14. Carpenter DO (2006) Polychlorinated biphenyls (PCBs): routes of exposure and effects on human health. Rev Environ Health 21:1–23CrossRefGoogle Scholar
  15. Chandrasekaran V, Lea C, Sosa JC, Higgins D, Lein PJ (2015) Reactive oxygen species are involved in BMP-induced dendritic growth in cultured rat sympathetic neurons. Mol Cell Neurosci 67:116–125. CrossRefGoogle Scholar
  16. Chen X, Lin Y, Dang K, Puschner B (2017) Quantification of polychlorinated biphenyls and polybrominated diphenyl ethers in commercial cows’ milk from California by gas chromatography-triple quadruple mass spectrometry. PLoS One 12:e0170129. CrossRefGoogle Scholar
  17. Cheslack-Postava K et al (2013) Maternal serum persistent organic pollutants in the Finnish Prenatal Study of Autism: a pilot study. Neurotoxicol Teratol 38:1–5. CrossRefGoogle Scholar
  18. Consonni D, Sindaco R, Bertazzi PA (2012) Blood levels of dioxins, furans, dioxin-like PCBs, and TEQs in general populations: a review, 1989-2010. Environ Int 44:151–162. CrossRefGoogle Scholar
  19. Copf T (2016) Impairments in dendrite morphogenesis as etiology for neurodevelopmental disorders and implications for therapeutic treatments. Neurosci Biobehav Rev 68:946–978. CrossRefGoogle Scholar
  20. Curran CP et al (2012) Ahrd Cyp1a2(-/-) mice show increased susceptibility to PCB-induced developmental neurotoxicity. Neurotoxicology 33:1436–1442. CrossRefGoogle Scholar
  21. D’Andrea I et al (2015) Lack of kinase-independent activity of PI3Kgamma in locus coeruleus induces ADHD symptoms through increased CREB signaling. EMBO Mol Med 7:904–917. CrossRefGoogle Scholar
  22. Dewailly E, Mulvad G, Pedersen HS, Ayotte P, Demers A, Weber JP, Hansen JC (1999) Concentration of organochlorines in human brain, liver, and adipose tissue autopsy samples from Greenland. Environ Health Perspect 107:823–828. CrossRefGoogle Scholar
  23. Do Y, Lee DK (2012) Effects of polychlorinated biphenyls on the development of neuronal cells in growth period; structure-activity relationship. Exp Neurobiol 21:30–36. CrossRefGoogle Scholar
  24. Engle EC (2010) Human genetic disorders of axon guidance. Cold Spring Harb Perspect Biol 2:a001784. CrossRefGoogle Scholar
  25. Eubig PA, Aguiar A, Schantz SL (2010) Lead and PCBs as risk factors for attention deficit/hyperactivity disorder. Environ Health Perspect 118:1654–1667. CrossRefGoogle Scholar
  26. Feng W et al (2017) Enantioselectivity of 2,2′,3,5′,6-pentachlorobiphenyl (PCB 95) atropisomers toward ryanodine receptors (RyRs) and their influences on hippocampal neuronal networks. Environ Sci Technol 51:14406–14416. CrossRefGoogle Scholar
  27. Frame GM, Cochran JW, Bowadt SS (1996) Complete PCB congener distributions for 17 aroclor mixtures determined by 3 HRGC systems optimized for comprehensive, quantitative, congener-specific analysis. J High Resolut Chromatogr 19:657–668CrossRefGoogle Scholar
  28. Fritsch EB, Pessah IN (2013) Structure-activity relationship of non-coplanar polychlorinated biphenyls toward skeletal muscle ryanodine receptors in rainbow trout (Oncorhynchus mykiss). Aquat Toxicol 140-141:204–212. CrossRefGoogle Scholar
  29. Gauger KJ, Kato Y, Haraguchi K, Lehmler HJ, Robertson LW, Bansal R, Zoeller RT (2004) Polychlorinated biphenyls (PCBs) exert thyroid hormone-like effects in the fetal rat brain but do not bind to thyroid hormone receptors. Environ Health Perspect 112:516–523. CrossRefGoogle Scholar
  30. Giera S, Bansal R, Ortiz-Toro TM, Taub DG, Zoeller RT (2011) Individual polychlorinated biphenyl (PCB) congeners produce tissue- and gene-specific effects on thyroid hormone signaling during development. Endocrinology 152:2909–2919. CrossRefGoogle Scholar
  31. Goldey ES, Crofton KM (1998) Thyroxine replacement attenuates hypothyroxinemia, hearing loss, and motor deficits following developmental exposure to Aroclor 1254 in rats. Toxicol Sci 45:94–105. CrossRefGoogle Scholar
  32. Granillo L et al (2019) Polychlorinated biphenyls influence on autism spectrum disorder risk in the MARBLES cohort. Environ Res 171:177–184. CrossRefGoogle Scholar
  33. Gregory P (2000) Industrial applications of phthalocyanines. J Porphyrins Phthalocyanines 04:432–437.<432::Aid-jpp254>3.0.Co;2-n CrossRefGoogle Scholar
  34. Grimm FA, He X, Teesch LM, Lehmler HJ, Robertson LW, Duffel MW (2015) Tissue distribution, metabolism, and excretion of 3,3′-dichloro-4′-sulfooxy-biphenyl in the rat. Environ Sci Technol 49:8087–8095. CrossRefGoogle Scholar
  35. Grimm FA et al (2017) Identification of a sulfate metabolite of PCB 11 in human serum. Environ Int 98:120–128. CrossRefGoogle Scholar
  36. Guo J, Capozzi SL, Kraeutler TM, Rodenburg LA (2014) Global distribution and local impacts of inadvertently generated polychlorinated biphenyls in pigments. Environ Sci Technol 48:8573–8580. CrossRefGoogle Scholar
  37. Hagmar L (2003) Polychlorinated biphenyls and thyroid status in humans: a review. Thyroid 13:1021–1028. CrossRefGoogle Scholar
  38. Hendriks HS, Antunes Fernandes EC, Bergman A, van den Berg M, Westerink RH (2010) PCB-47, PBDE-47, and 6-OH-PBDE-47 differentially modulate human GABAA and alpha4beta2 nicotinic acetylcholine receptors. Toxicol Sci 118:635–642. CrossRefGoogle Scholar
  39. Hertz-Picciotto I et al (2018) A prospective study of environmental exposures and early biomarkers in autism spectrum disorder: design, protocols, and preliminary data from the MARBLES Study. Environ Health Perspect 126:117004. CrossRefGoogle Scholar
  40. Holland EB, Feng W, Zheng J, Dong Y, Li X, Lehmler HJ, Pessah IN (2017) An extended structure-activity relationship of nondioxin-like PCBs evaluates and supports modeling predictions and identifies picomolar potency of PCB 202 towards ryanodine receptors. Toxicol Sci 155:170–181. CrossRefGoogle Scholar
  41. Hopf NB, Ruder AM, Succop P (2009) Background levels of polychlorinated biphenyls in the U.S. population. Sci Total Environ 407:6109–6119. CrossRefGoogle Scholar
  42. Hornbuckle K, Robertson L (2010) Polychlorinated biphenyls (PCBs): sources, exposures, toxicities. Environ Sci Technol 44:2749–2751. CrossRefGoogle Scholar
  43. Hsu ST, Ma CI, Hsu SK, Wu SS, Hsu NH, Yeh CC, Wu SB (1985) Discovery and epidemiology of PCB poisoning in Taiwan: a four-year followup. Environ Health Perspect 59:5–10. CrossRefGoogle Scholar
  44. Hu D, Hornbuckle KC (2010) Inadvertent polychlorinated biphenyls in commercial paint pigments. Environ Sci Technol 44:2822–2827. CrossRefGoogle Scholar
  45. Hu D, Martinez A, Hornbuckle KC (2008) Discovery of non-aroclor PCB (3,3′-dichlorobiphenyl) in Chicago air. Environ Sci Technol 42:7873–7877CrossRefGoogle Scholar
  46. Inglefield JR, Shafer TJ (2000) Polychlorinated biphenyl-stimulation of Ca(2+) oscillations in developing neocortical cells: a role for excitatory transmitters and L-type voltage-sensitive Ca(2+) channels. J Pharmacol Exp Ther 295:105–113Google Scholar
  47. Inglefield JR, Mundy WR, Shafer TJ (2001) Inositol 1,4,5-triphosphate receptor-sensitive Ca(2+) release, store-operated Ca(2+) entry, and cAMP responsive element binding protein phosphorylation in developing cortical cells following exposure to polychlorinated biphenyls. J Pharmacol Exp Ther 297:762–773Google Scholar
  48. Itoh S et al (2018) Association of maternal serum concentration of hydroxylated polychlorinated biphenyls with maternal and neonatal thyroid hormones: The Hokkaido birth cohort study. Environ Res 167:583–590. CrossRefGoogle Scholar
  49. Iwasaki T, Miyazaki W, Takeshita A, Kuroda Y, Koibuchi N (2002) Polychlorinated biphenyls suppress thyroid hormone-induced transactivation. Biochem Biophys Res Commun 299:384–388. CrossRefGoogle Scholar
  50. Jensen S (1972) The PCB Story. Ambio 1:123–131Google Scholar
  51. Keil KP, Sethi S, Lein PJ (2019) Sex-dependent effects of 2,2′,3,5′,6-pentachlorobiphenyl on dendritic arborization of primary mouse neurons. Toxicol Sci 168:95–109. CrossRefGoogle Scholar
  52. Klinefelter K et al (2018) Genetic differences in the aryl hydrocarbon receptor and CYP1A2 affect sensitivity to developmental polychlorinated biphenyl exposure in mice: relevance to studies of human neurological disorders. Mamm Genome 29:112–127. CrossRefGoogle Scholar
  53. Kodavanti PR, Tilson HA (2000) Neurochemical effects of environmental chemicals: in vitro and in vivo correlations on second messenger pathways. Ann N Y Acad Sci 919:97–105CrossRefGoogle Scholar
  54. Koh WX, Hornbuckle KC, Thorne PS (2015) Human serum from urban and rural adolescents and their mothers shows exposure to polychlorinated biphenyls not found in commercial mixtures. Environ Sci Technol 49:8105–8112. CrossRefGoogle Scholar
  55. Koh WX, Hornbuckle KC, Marek RF, Wang K, Thorne PS (2016) Hydroxylated polychlorinated biphenyls in human sera from adolescents and their mothers living in two U.S. Midwestern communities. Chemosphere 147:389–395. CrossRefGoogle Scholar
  56. Kouidhi S, Clerget-Froidevaux MS (2018) Integrating Thyroid hormone signaling in hypothalamic control of metabolism: crosstalk between nuclear receptors. Int J Mol Sci:19. CrossRefGoogle Scholar
  57. Lehmann GM, Christensen K, Maddaloni M, Phillips LJ (2015) Evaluating health risks from inhaled polychlorinated biphenyls: research needs for addressing uncertainty. Environ Health Perspect 123:109–113. CrossRefGoogle Scholar
  58. Lesiak A, Zhu M, Chen H, Appleyard SM, Impey S, Lein PJ, Wayman GA (2014) The environmental neurotoxicant PCB 95 promotes synaptogenesis via ryanodine receptor-dependent miR132 upregulation. J Neurosci 34:717–725. CrossRefGoogle Scholar
  59. Li ZM et al (2018) Association of in utero persistent organic pollutant exposure with placental thyroid hormones. Endocrinology 159:3473–3481. CrossRefGoogle Scholar
  60. Libersat F, Duch C (2004) Mechanisms of dendritic maturation. Mol Neurobiol 29:303–320. CrossRefGoogle Scholar
  61. Llansola M, Piedrafita B, Rodrigo R, Montoliu C, Felipo V (2009) Polychlorinated biphenyls PCB 153 and PCB 126 impair the glutamate-nitric oxide-cGMP pathway in cerebellar neurons in culture by different mechanisms. Neurotox Res 16:97–105. CrossRefGoogle Scholar
  62. Llansola M, Montoliu C, Boix J, Felipo V (2010) Polychlorinated biphenyls PCB 52, PCB 180, and PCB 138 impair the glutamate-nitric oxide-cGMP pathway in cerebellar neurons in culture by different mechanisms. Chem Res Toxicol 23:813–820. CrossRefGoogle Scholar
  63. Londono M, Shimokawa N, Miyazaki W, Iwasaki T, Koibuchi N (2010) Hydroxylated PCB induces Ca2+ oscillations and alterations of membrane potential in cultured cortical cells. J Appl Toxicol 30:334–342. CrossRefGoogle Scholar
  64. Longnecker MP et al (2003) Comparison of polychlorinated biphenyl levels across studies of human neurodevelopment. Environ Health Perspect 111:65–70. CrossRefGoogle Scholar
  65. Lyall K, Croen LA, Sjodin A, Yoshida CK, Zerbo O, Kharrazi M, Windham GC (2017) Polychlorinated biphenyl and organochlorine pesticide concentrations in maternal mid-pregnancy serum samples: association with autism spectrum disorder and intellectual disability. Environ Health Perspect 125:474–480. CrossRefGoogle Scholar
  66. Marek RF, Thorne PS, Wang K, Dewall J, Hornbuckle KC (2013) PCBs and OH-PCBs in serum from children and mothers in urban and rural U.S. communities. Environ Sci Technol 47:3353–3361. CrossRefGoogle Scholar
  67. Martin L, Klaassen CD (2010) Differential effects of polychlorinated biphenyl congeners on serum thyroid hormone levels in rats. Toxicol Sci 117:36–44. CrossRefGoogle Scholar
  68. McIntyre JK, Beauchamp DA (2007) Age and trophic position dominate bioaccumulation of mercury and organochlorines in the food web of Lake Washington. Sci Total Environ 372:571–584. CrossRefGoogle Scholar
  69. Mitchell MM, Woods R, Chi LH, Schmidt RJ, Pessah IN, Kostyniak PJ, LaSalle JM (2012) Levels of select PCB and PBDE congeners in human postmortem brain reveal possible environmental involvement in 15q11-q13 duplication autism spectrum disorder. Environ Mol Mutagen 53:589–598. CrossRefGoogle Scholar
  70. Mitoma C et al (2015) Yusho and its latest findings-A review in studies conducted by the Yusho Group. Environ Int 82:41–48. CrossRefGoogle Scholar
  71. Miyazaki W, Iwasaki T, Takeshita A, Tohyama C, Koibuchi N (2008) Identification of the functional domain of thyroid hormone receptor responsible for polychlorinated biphenyl-mediated suppression of its action in vitro. Environ Health Perspect 116:1231–1236. CrossRefGoogle Scholar
  72. Mundy WR, Shafer TJ, Tilson HA, Kodavanti PR (1999) Extracellular calcium is required for the polychlorinated biphenyl-induced increase of intracellular free calcium levels in cerebellar granule cell culture. Toxicology 136:27–39CrossRefGoogle Scholar
  73. Nave KA, Werner HB (2014) Myelination of the nervous system: mechanisms and functions. Annu Rev Cell Dev Biol 30:503–533. CrossRefGoogle Scholar
  74. Naveau E, Pinson A, Gérard A, Nguyen L, Charlier C, Thomé JP, Zoeller RT, Bourguignon JP, Parent AS (2014) Alteration of rat fetal cerebral cortex development after prenatal exposure to polychlorinated biphenyls. PLoS One 9:e91903. CrossRefGoogle Scholar
  75. Ngounou Wetie AG, Wormwood KL, Charette L, Ryan JP, Woods AG, Darie CC (2015) Comparative two-dimensional polyacrylamide gel electrophoresis of the salivary proteome of children with autism spectrum disorder. J Cell Mol Med 19:2664–2678. CrossRefGoogle Scholar
  76. Parent AS et al (2016) Early exposure to Aroclor 1254 in vivo disrupts the functional synaptic development of newborn hippocampal granule cells. Eur J Neurosci 44:3001–3010. CrossRefGoogle Scholar
  77. Pencikova K et al (2018) In vitro profiling of toxic effects of prominent environmental lower-chlorinated PCB congeners linked with endocrine disruption and tumor promotion. Environ Pollut 237:473–486. CrossRefGoogle Scholar
  78. Penzes P, Cahill ME, Jones KA, VanLeeuwen JE, Woolfrey KM (2011) Dendritic spine pathology in neuropsychiatric disorders. Nat Neurosci 14:285–293. CrossRefGoogle Scholar
  79. Pessah IN, Lehmler HJ, Robertson LW, Perez CF, Cabrales E, Bose DD, Feng W (2009) Enantiomeric specificity of (-)-2,2′,3,3′,6,6′-hexachlorobiphenyl toward ryanodine receptor types 1 and 2. Chem Res Toxicol 22:201–207. CrossRefGoogle Scholar
  80. Pessah IN, Cherednichenko G, Lein PJ (2010) Minding the calcium store: ryanodine receptor activation as a convergent mechanism of PCB toxicity. Pharmacol Ther 125:260–285. CrossRefGoogle Scholar
  81. Pessah IN, Lein PJ, Seegal RF, Sagiv SK (2019) Neurotoxicity of polychlorinated biphenyls and related organohalogens. Acta Neuropathol. CrossRefGoogle Scholar
  82. Pinson A, Bourguignon JP, Parent AS (2016) Exposure to endocrine disrupting chemicals and neurodevelopmental alterations. Andrology 4:706–722. CrossRefGoogle Scholar
  83. Pittenger C, Kandel ER (2003) In search of general mechanisms for long-lasting plasticity: aplysia and the hippocampus. Philos Trans R Soc Lond Ser B Biol Sci 358:757–763. CrossRefGoogle Scholar
  84. Redmond L, Kashani AH, Ghosh A (2002) Calcium regulation of dendritic growth via CaM kinase IV and CREB-mediated transcription. Neuron 34:999–1010CrossRefGoogle Scholar
  85. Rosenquist AH et al (2017) Prenatal and postnatal PCB-153 and p,p′-DDE exposures and behavior scores at 5-9 years of age among children in Greenland and Ukraine. Environ Health Perspect 125:107002. CrossRefGoogle Scholar
  86. Rovet JF (2014) The role of thyroid hormones for brain development and cognitive function. Endocr Dev 26:26–43. CrossRefGoogle Scholar
  87. Royland JE, Kodavanti PR (2008) Gene expression profiles following exposure to a developmental neurotoxicant, Aroclor 1254: pathway analysis for possible mode(s) of action. Toxicol Appl Pharmacol 231:179–196. CrossRefGoogle Scholar
  88. Sable HJK, Schantz SL (2006) Executive function following developmental exposure to polychlorinated biphenyls (PCBs): what animal models have told us. In: Levin ED, Buccafusco JJ (eds) Animal Models of Cognitive Impairment. Frontiers in Neuroscience, Boca RatonGoogle Scholar
  89. Sagiv SK, Thurston SW, Bellinger DC, Tolbert PE, Altshul LM, Korrick SA (2010) Prenatal organochlorine exposure and behaviors associated with attention deficit hyperactivity disorder in school-aged children. Am J Epidemiol 171:593–601. CrossRefGoogle Scholar
  90. Samso M, Feng W, Pessah IN, Allen PD (2009) Coordinated movement of cytoplasmic and transmembrane domains of RyR1 upon gating. PLoS Biol 7:e85. CrossRefGoogle Scholar
  91. Schantz SL, Seo BW, Moshtaghian J, Peterson RE, Moore RW (1996) Effects of gestational and lactational exposure to TCDD or coplanar PCBs on spatial learning. Neurotoxicol Teratol 18:305–313CrossRefGoogle Scholar
  92. Schantz SL, Widholm JJ, Rice DC (2003) Effects of PCB exposure on neuropsychological function in children. Environ Health Perspect 111:357–576. CrossRefGoogle Scholar
  93. Scott EK, Luo L (2001) How do dendrites take their shape? Nat Neurosci 4:359–365. CrossRefGoogle Scholar
  94. Sethi S et al (2017a) Detection of 3,3′-dichlorobiphenyl in human maternal plasma and its effects on axonal and dendritic growth in primary rat neurons. Toxicol Sci 158:401–411. CrossRefGoogle Scholar
  95. Sethi S, Keil KP, Lein PJ (2017b) Species and sex differences in the morphogenic response of primary rodent neurons to 3,3′-dichlorobiphenyl (PCB 11). Toxics 6.
  96. Sethi S, Keil KP, Lein PJ (2018) 3,3′-Dichlorobiphenyl (PCB 11) promotes dendritic arborization in primary rat cortical neurons via a CREB-dependent mechanism. Arch Toxicol 92:3337–3345. CrossRefGoogle Scholar
  97. Sethi S et al (2019) Comparative analyses of the 12 most abundant PCB congeners detected in human maternal serum for activity at the thyroid hormone receptor and ryanodine receptor. Environ Sci Technol 53:3948–3958. CrossRefGoogle Scholar
  98. Shang H, Li Y, Wang T, Wang P, Zhang H, Zhang Q, Jiang G (2014) The presence of polychlorinated biphenyls in yellow pigment products in China with emphasis on 3,3′-dichlorobiphenyl (PCB 11). Chemosphere 98:44–50. CrossRefGoogle Scholar
  99. Stamou M, Streifel KM, Goines PE, Lein PJ (2013) Neuronal connectivity as a convergent target of gene x environment interactions that confer risk for autism spectrum disorders. Neurotoxicol Teratol 36:3–16. CrossRefGoogle Scholar
  100. Stolz A (2001) Basic and applied aspects in the microbial degradation of azo dyes. Appl Microbiol Biotechnol 56:69–80. CrossRefGoogle Scholar
  101. Supekar K et al (2013) Brain hyperconnectivity in children with autism and its links to social deficits. Cell Rep 5:738–747. CrossRefGoogle Scholar
  102. Takeuchi S, Anezaki K, Kojima H (2017) Effects of unintentional PCBs in pigments and chemical products on transcriptional activity via aryl hydrocarbon and nuclear hormone receptors. Environ Pollut 227:306–313. CrossRefGoogle Scholar
  103. Thomas K, Xue J, Williams R, Jones P, Whitaker D (2012) Polychlorinated biphenyls (PCBs) in school buildings: sources, environmental levels, and exposures. United States Environmental Protection AgencyGoogle Scholar
  104. Todd PK, Mack KJ (2001) Phosphorylation, CREB, and mental retardation. Pediatr Res 50:672. CrossRefGoogle Scholar
  105. Wadzinski TL, Geromini K, McKinley Brewer J, Bansal R, Abdelouahab N, Langlois MF, Takser L, Zoeller RT (2014) Endocrine disruption in human placenta: expression of the dioxin-inducible enzyme, CYP1A1, is correlated with that of thyroid hormone-regulated genes. J Clin Endocrinol Metab 99:E2735–E2743CrossRefGoogle Scholar
  106. Wayman GA, Impey S, Marks D, Saneyoshi T, Grant WF, Derkach V, Soderling TR (2006) Activity-dependent dendritic arborization mediated by CaM-kinase I activation and enhanced CREB-dependent transcription of Wnt-2. Neuron 50:897–909. CrossRefGoogle Scholar
  107. Wayman GA et al (2008) An activity-regulated microRNA controls dendritic plasticity by down-regulating p250GAP. Proc Natl Acad Sci U S A 105:9093–9098. CrossRefGoogle Scholar
  108. Wayman GA et al (2012a) PCB-95 modulates the calcium-dependent signaling pathway responsible for activity-dependent dendritic growth. Environ Health Perspect 120:1003–1009. CrossRefGoogle Scholar
  109. Wayman GA et al (2012b) PCB-95 promotes dendritic growth via ryanodine receptor-dependent mechanisms. Environ Health Perspect 120:997–1002. CrossRefGoogle Scholar
  110. White SS, Birnbaum LS (2009) An overview of the effects of dioxins and dioxin-like compounds on vertebrates, as documented in human and ecological epidemiology. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 27:197–211. CrossRefGoogle Scholar
  111. Winneke G (2011) Developmental aspects of environmental neurotoxicology: lessons from lead and polychlorinated biphenyls. J Neurol Sci 308:9–15. CrossRefGoogle Scholar
  112. Wong PW, Joy RM, Albertson TE, Schantz SL, Pessah IN (1997) Ortho-substituted 2,2′,3,5′,6-pentachlorobiphenyl (PCB 95) alters rat hippocampal ryanodine receptors and neuroplasticity in vitro: evidence for altered hippocampal function. Neurotoxicology 18:443–456Google Scholar
  113. Yang JH, Kodavanti PR (2001) Possible molecular targets of halogenated aromatic hydrocarbons in neuronal cells. Biochem Biophys Res Commun 280:1372–1377. CrossRefGoogle Scholar
  114. Yang D et al (2009) Developmental exposure to polychlorinated biphenyls interferes with experience-dependent dendritic plasticity and ryanodine receptor expression in weanling rats. Environ Health Perspect 117:426–435. CrossRefGoogle Scholar
  115. Yang D et al (2014) PCB 136 atropselectively alters morphometric and functional parameters of neuronal connectivity in cultured rat hippocampal neurons via ryanodine receptor-dependent mechanisms. Toxicol Sci 138:379–392. CrossRefGoogle Scholar
  116. Zahalka EA, Ellis DH, Goldey ES, Stanton ME, Lau C (2001) Perinatal exposure to polychlorinated biphenyls Aroclor 1016 or 1254 did not alter brain catecholamines nor delayed alternation performance in Long-Evans rats. Brain Res Bull 55:487–500CrossRefGoogle Scholar
  117. Zimmer KE, Gutleb AC, Lyche JL, Dahl E, Oskam IC, Krogenaes A, Skaare JU, Ropstad E (2009) Altered stress-induced cortisol levels in goats exposed to polychlorinated biphenyls (PCB 126 and PCB 153) during fetal and postnatal development. J Toxicol Environ Health A 72:164–172. CrossRefGoogle Scholar
  118. Zoeller RT (2007) Environmental chemicals impacting the thyroid: targets and consequences. Thyroid 17:811–817. CrossRefGoogle Scholar
  119. Zoeller TR, Dowling AL, Herzig CT, Iannacone EA, Gauger KJ, Bansal R (2002) Thyroid hormone, brain development, and the environment. Environ Health Perspect 110(Suppl 3):355–361. CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Molecular BiosciencesUniversity of California, Davis School of Veterinary MedicineDavisUSA

Personalised recommendations