Developmental exposure to polychlorinated biphenyls interferes with experience-dependent dendritic plasticity and ryanodine receptor expression in weanling rats

Dongren Yang, Kyung Ho Kim, Andrew Phimister, Adam D. Bachstetter, Thomas R. Ward, Robert W. Stackman, Ronald F. Mervis, Amy B. Wisniewski, Sabra L Klein, Prasada Rao S Kodavanti, Kim A. Anderson, Gary Wayman, Isaac N. Pessah, Pamela J. Lein

Research output: Contribution to journalArticle

Abstract

Background: Neurodevelopmental disorders are associated with altered patterns of neuronal connectivity. A critical determinant of neuronal connectivity is the dendritic morphology of individual neurons, which is shaped by experience. The identification of environmental exposures that interfere with dendritic growth and plasticity may, therefore, provide insight into environmental risk factors for neurodevelopmental disorders. Objective: We tested the hypothesis that polychlorinated biphenyls (PCBs) alter dendritic growth and/or plasticity by promoting the activity of ryanodine receptors (RyRs). Methods and Results: The Morris water maze was used to induce experience-dependent neural plasticity in weanling rats exposed to either vehicle or Aroclor 1254 (A1254) in the maternal diet throughout gestation and lactation. Developmental A1254 exposure promoted dendritic growth in cerebellar Purkinje cells and neocortical pyramidal neurons among untrained animals but attenuated or reversed experience-dependent dendritic growth among maze-trained littermates. These structural changes coincided with subtle deficits in spatial learning and memory, increased [3H]-ryanodine binding sites and RyR expression in the cerebellum of untrained animals, and inhibition of training-induced RyR upregulation. A congener with potent RyR activity, PCB95, but not a congener with negligible RyR activity, PCB66, promoted dendritic growth in primary cortical neuron cultures and this effect was blocked by pharmacologic antagonism of RyR activity. Conclusions: Developmental exposure to PCBs interferes with normal patterns of dendritic growth and plasticity, and these effects may be linked to changes in RyR expression and function. These findings identify PCBs as candidate environmental risk factors for neurodevelopmental disorders, especially in children with heritable deficits in calcium signaling.

Original languageEnglish (US)
Pages (from-to)426-435
Number of pages10
JournalEnvironmental Health Perspectives
Volume117
Issue number3
DOIs
StatePublished - 2009

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Ryanodine Receptor Calcium Release Channel
Polychlorinated Biphenyls
Growth
Chlorodiphenyl (54% Chlorine)
Neurons
Ryanodine
Neuronal Plasticity
Calcium Signaling
Pyramidal Cells
Purkinje Cells
Environmental Exposure
Lactation
Cerebellum
Up-Regulation
Binding Sites
Mothers
Diet
Pregnancy
Water
Neurodevelopmental Disorders

Keywords

  • Dendrite
  • Developmental neurotoxicity
  • Neurodevelopmental disorders
  • PCBs
  • Plasticity
  • Tyanodine receptor

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Public Health, Environmental and Occupational Health

Cite this

Developmental exposure to polychlorinated biphenyls interferes with experience-dependent dendritic plasticity and ryanodine receptor expression in weanling rats. / Yang, Dongren; Kim, Kyung Ho; Phimister, Andrew; Bachstetter, Adam D.; Ward, Thomas R.; Stackman, Robert W.; Mervis, Ronald F.; Wisniewski, Amy B.; Klein, Sabra L; Kodavanti, Prasada Rao S; Anderson, Kim A.; Wayman, Gary; Pessah, Isaac N.; Lein, Pamela J.

In: Environmental Health Perspectives, Vol. 117, No. 3, 2009, p. 426-435.

Research output: Contribution to journalArticle

Yang, D, Kim, KH, Phimister, A, Bachstetter, AD, Ward, TR, Stackman, RW, Mervis, RF, Wisniewski, AB, Klein, SL, Kodavanti, PRS, Anderson, KA, Wayman, G, Pessah, IN & Lein, PJ 2009, 'Developmental exposure to polychlorinated biphenyls interferes with experience-dependent dendritic plasticity and ryanodine receptor expression in weanling rats', Environmental Health Perspectives, vol. 117, no. 3, pp. 426-435. https://doi.org/10.1289/ehp.11771
Yang, Dongren ; Kim, Kyung Ho ; Phimister, Andrew ; Bachstetter, Adam D. ; Ward, Thomas R. ; Stackman, Robert W. ; Mervis, Ronald F. ; Wisniewski, Amy B. ; Klein, Sabra L ; Kodavanti, Prasada Rao S ; Anderson, Kim A. ; Wayman, Gary ; Pessah, Isaac N. ; Lein, Pamela J. / Developmental exposure to polychlorinated biphenyls interferes with experience-dependent dendritic plasticity and ryanodine receptor expression in weanling rats. In: Environmental Health Perspectives. 2009 ; Vol. 117, No. 3. pp. 426-435.
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abstract = "Background: Neurodevelopmental disorders are associated with altered patterns of neuronal connectivity. A critical determinant of neuronal connectivity is the dendritic morphology of individual neurons, which is shaped by experience. The identification of environmental exposures that interfere with dendritic growth and plasticity may, therefore, provide insight into environmental risk factors for neurodevelopmental disorders. Objective: We tested the hypothesis that polychlorinated biphenyls (PCBs) alter dendritic growth and/or plasticity by promoting the activity of ryanodine receptors (RyRs). Methods and Results: The Morris water maze was used to induce experience-dependent neural plasticity in weanling rats exposed to either vehicle or Aroclor 1254 (A1254) in the maternal diet throughout gestation and lactation. Developmental A1254 exposure promoted dendritic growth in cerebellar Purkinje cells and neocortical pyramidal neurons among untrained animals but attenuated or reversed experience-dependent dendritic growth among maze-trained littermates. These structural changes coincided with subtle deficits in spatial learning and memory, increased [3H]-ryanodine binding sites and RyR expression in the cerebellum of untrained animals, and inhibition of training-induced RyR upregulation. A congener with potent RyR activity, PCB95, but not a congener with negligible RyR activity, PCB66, promoted dendritic growth in primary cortical neuron cultures and this effect was blocked by pharmacologic antagonism of RyR activity. Conclusions: Developmental exposure to PCBs interferes with normal patterns of dendritic growth and plasticity, and these effects may be linked to changes in RyR expression and function. These findings identify PCBs as candidate environmental risk factors for neurodevelopmental disorders, especially in children with heritable deficits in calcium signaling.",
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AU - Kim, Kyung Ho

AU - Phimister, Andrew

AU - Bachstetter, Adam D.

AU - Ward, Thomas R.

AU - Stackman, Robert W.

AU - Mervis, Ronald F.

AU - Wisniewski, Amy B.

AU - Klein, Sabra L

AU - Kodavanti, Prasada Rao S

AU - Anderson, Kim A.

AU - Wayman, Gary

AU - Pessah, Isaac N.

AU - Lein, Pamela J.

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