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Developmental Exposure to Polychlorinated Biphenyls Interferes with Experience-Dependent Dendritic Plasticity and Ryanodine Receptor Expression in Weanling Rats
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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
National Institute of Environmental Health Sciences
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2661913/ https://www.ncbi.nlm.nih.gov/pubmed/19337518 http://dx.doi.org/10.1289/ehp.11771 |
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author | 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. |
author_facet | 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. |
author_sort | Yang, Dongren |
collection | PubMed |
description | 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 [(3)H]-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. |
format | Text |
id | pubmed-2661913 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | National Institute of Environmental Health Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-26619132009-03-31 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. Environ Health Perspect Research 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 [(3)H]-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. National Institute of Environmental Health Sciences 2009-03 2008-09-12 /pmc/articles/PMC2661913/ /pubmed/19337518 http://dx.doi.org/10.1289/ehp.11771 Text en http://creativecommons.org/publicdomain/mark/1.0/ Publication of EHP lies in the public domain and is therefore without copyright. All text from EHP may be reprinted freely. Use of materials published in EHP should be acknowledged (for example, ?Reproduced with permission from Environmental Health Perspectives?); pertinent reference information should be provided for the article from which the material was reproduced. Articles from EHP, especially the News section, may contain photographs or illustrations copyrighted by other commercial organizations or individuals that may not be used without obtaining prior approval from the holder of the copyright. |
spellingShingle | Research 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 |
title | Developmental Exposure to Polychlorinated Biphenyls Interferes with Experience-Dependent Dendritic Plasticity and Ryanodine Receptor Expression in Weanling Rats |
title_full | Developmental Exposure to Polychlorinated Biphenyls Interferes with Experience-Dependent Dendritic Plasticity and Ryanodine Receptor Expression in Weanling Rats |
title_fullStr | Developmental Exposure to Polychlorinated Biphenyls Interferes with Experience-Dependent Dendritic Plasticity and Ryanodine Receptor Expression in Weanling Rats |
title_full_unstemmed | Developmental Exposure to Polychlorinated Biphenyls Interferes with Experience-Dependent Dendritic Plasticity and Ryanodine Receptor Expression in Weanling Rats |
title_short | Developmental Exposure to Polychlorinated Biphenyls Interferes with Experience-Dependent Dendritic Plasticity and Ryanodine Receptor Expression in Weanling Rats |
title_sort | developmental exposure to polychlorinated biphenyls interferes with experience-dependent dendritic plasticity and ryanodine receptor expression in weanling rats |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2661913/ https://www.ncbi.nlm.nih.gov/pubmed/19337518 http://dx.doi.org/10.1289/ehp.11771 |
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