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Persistent autism-relevant behavioral phenotype and social neuropeptide alterations in female mice offspring induced by maternal transfer of PBDE congeners in the commercial mixture DE-71
Polybrominated diphenyl ethers (PBDEs) are ubiquitous persistent organic pollutants (POPs) that are known neuroendocrine disrupting chemicals with adverse neurodevelopmental effects. PBDEs may act as risk factors for autism spectrum disorders (ASD), characterized by abnormal psychosocial functioning...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8536480/ https://www.ncbi.nlm.nih.gov/pubmed/34687351 http://dx.doi.org/10.1007/s00204-021-03163-4 |
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author | Kozlova, Elena V. Valdez, Matthew C. Denys, Maximillian E. Bishay, Anthony E. Krum, Julia M. Rabbani, Kayhon M. Carrillo, Valeria Gonzalez, Gwendolyn M. Lampel, Gregory Tran, Jasmin D. Vazquez, Brigitte M. Anchondo, Laura M. Uddin, Syed A. Huffman, Nicole M. Monarrez, Eduardo Olomi, Duraan S. Chinthirla, Bhuvaneswari D. Hartman, Richard E. Kodavanti, Prasada Rao S. Chompre, Gladys Phillips, Allison L. Stapleton, Heather M. Henkelmann, Bernhard Schramm, Karl-Werner Curras-Collazo, Margarita C. |
author_facet | Kozlova, Elena V. Valdez, Matthew C. Denys, Maximillian E. Bishay, Anthony E. Krum, Julia M. Rabbani, Kayhon M. Carrillo, Valeria Gonzalez, Gwendolyn M. Lampel, Gregory Tran, Jasmin D. Vazquez, Brigitte M. Anchondo, Laura M. Uddin, Syed A. Huffman, Nicole M. Monarrez, Eduardo Olomi, Duraan S. Chinthirla, Bhuvaneswari D. Hartman, Richard E. Kodavanti, Prasada Rao S. Chompre, Gladys Phillips, Allison L. Stapleton, Heather M. Henkelmann, Bernhard Schramm, Karl-Werner Curras-Collazo, Margarita C. |
author_sort | Kozlova, Elena V. |
collection | PubMed |
description | Polybrominated diphenyl ethers (PBDEs) are ubiquitous persistent organic pollutants (POPs) that are known neuroendocrine disrupting chemicals with adverse neurodevelopmental effects. PBDEs may act as risk factors for autism spectrum disorders (ASD), characterized by abnormal psychosocial functioning, although direct evidence is currently lacking. Using a translational exposure model, we tested the hypothesis that maternal transfer of a commercial mixture of PBDEs, DE-71, produces ASD-relevant behavioral and neurochemical deficits in female offspring. C57Bl6/N mouse dams (F0) were exposed to DE-71 via oral administration of 0 (VEH/CON), 0.1 (L-DE-71) or 0.4 (H-DE-71) mg/kg bw/d from 3 wk prior to gestation through end of lactation. Mass spectrometry analysis indicated in utero and lactational transfer of PBDEs (in ppb) to F1 female offspring brain tissue at postnatal day (PND) 15 which was reduced by PND 110. Neurobehavioral testing of social novelty preference (SNP) and social recognition memory (SRM) revealed that adult L-DE-71 F1 offspring display deficient short- and long-term SRM, in the absence of reduced sociability, and increased repetitive behavior. These effects were concomitant with reduced olfactory discrimination of social odors. Additionally, L-DE-71 exposure also altered short-term novel object recognition memory but not anxiety or depressive-like behavior. Moreover, F1 L-DE-71 displayed downregulated mRNA transcripts for oxytocin (Oxt) in the bed nucleus of the stria terminalis (BNST) and supraoptic nucleus, and vasopressin (Avp) in the BNST and upregulated Avp1ar in BNST, and Oxtr in the paraventricular nucleus. Our work demonstrates that developmental PBDE exposure produces ASD-relevant neurochemical, olfactory processing and behavioral phenotypes that may result from early neurodevelopmental reprogramming within central social and memory networks. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00204-021-03163-4. |
format | Online Article Text |
id | pubmed-8536480 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-85364802021-10-25 Persistent autism-relevant behavioral phenotype and social neuropeptide alterations in female mice offspring induced by maternal transfer of PBDE congeners in the commercial mixture DE-71 Kozlova, Elena V. Valdez, Matthew C. Denys, Maximillian E. Bishay, Anthony E. Krum, Julia M. Rabbani, Kayhon M. Carrillo, Valeria Gonzalez, Gwendolyn M. Lampel, Gregory Tran, Jasmin D. Vazquez, Brigitte M. Anchondo, Laura M. Uddin, Syed A. Huffman, Nicole M. Monarrez, Eduardo Olomi, Duraan S. Chinthirla, Bhuvaneswari D. Hartman, Richard E. Kodavanti, Prasada Rao S. Chompre, Gladys Phillips, Allison L. Stapleton, Heather M. Henkelmann, Bernhard Schramm, Karl-Werner Curras-Collazo, Margarita C. Arch Toxicol Developmental Toxicology Polybrominated diphenyl ethers (PBDEs) are ubiquitous persistent organic pollutants (POPs) that are known neuroendocrine disrupting chemicals with adverse neurodevelopmental effects. PBDEs may act as risk factors for autism spectrum disorders (ASD), characterized by abnormal psychosocial functioning, although direct evidence is currently lacking. Using a translational exposure model, we tested the hypothesis that maternal transfer of a commercial mixture of PBDEs, DE-71, produces ASD-relevant behavioral and neurochemical deficits in female offspring. C57Bl6/N mouse dams (F0) were exposed to DE-71 via oral administration of 0 (VEH/CON), 0.1 (L-DE-71) or 0.4 (H-DE-71) mg/kg bw/d from 3 wk prior to gestation through end of lactation. Mass spectrometry analysis indicated in utero and lactational transfer of PBDEs (in ppb) to F1 female offspring brain tissue at postnatal day (PND) 15 which was reduced by PND 110. Neurobehavioral testing of social novelty preference (SNP) and social recognition memory (SRM) revealed that adult L-DE-71 F1 offspring display deficient short- and long-term SRM, in the absence of reduced sociability, and increased repetitive behavior. These effects were concomitant with reduced olfactory discrimination of social odors. Additionally, L-DE-71 exposure also altered short-term novel object recognition memory but not anxiety or depressive-like behavior. Moreover, F1 L-DE-71 displayed downregulated mRNA transcripts for oxytocin (Oxt) in the bed nucleus of the stria terminalis (BNST) and supraoptic nucleus, and vasopressin (Avp) in the BNST and upregulated Avp1ar in BNST, and Oxtr in the paraventricular nucleus. Our work demonstrates that developmental PBDE exposure produces ASD-relevant neurochemical, olfactory processing and behavioral phenotypes that may result from early neurodevelopmental reprogramming within central social and memory networks. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00204-021-03163-4. Springer Berlin Heidelberg 2021-10-23 2022 /pmc/articles/PMC8536480/ /pubmed/34687351 http://dx.doi.org/10.1007/s00204-021-03163-4 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Developmental Toxicology Kozlova, Elena V. Valdez, Matthew C. Denys, Maximillian E. Bishay, Anthony E. Krum, Julia M. Rabbani, Kayhon M. Carrillo, Valeria Gonzalez, Gwendolyn M. Lampel, Gregory Tran, Jasmin D. Vazquez, Brigitte M. Anchondo, Laura M. Uddin, Syed A. Huffman, Nicole M. Monarrez, Eduardo Olomi, Duraan S. Chinthirla, Bhuvaneswari D. Hartman, Richard E. Kodavanti, Prasada Rao S. Chompre, Gladys Phillips, Allison L. Stapleton, Heather M. Henkelmann, Bernhard Schramm, Karl-Werner Curras-Collazo, Margarita C. Persistent autism-relevant behavioral phenotype and social neuropeptide alterations in female mice offspring induced by maternal transfer of PBDE congeners in the commercial mixture DE-71 |
title | Persistent autism-relevant behavioral phenotype and social neuropeptide alterations in female mice offspring induced by maternal transfer of PBDE congeners in the commercial mixture DE-71 |
title_full | Persistent autism-relevant behavioral phenotype and social neuropeptide alterations in female mice offspring induced by maternal transfer of PBDE congeners in the commercial mixture DE-71 |
title_fullStr | Persistent autism-relevant behavioral phenotype and social neuropeptide alterations in female mice offspring induced by maternal transfer of PBDE congeners in the commercial mixture DE-71 |
title_full_unstemmed | Persistent autism-relevant behavioral phenotype and social neuropeptide alterations in female mice offspring induced by maternal transfer of PBDE congeners in the commercial mixture DE-71 |
title_short | Persistent autism-relevant behavioral phenotype and social neuropeptide alterations in female mice offspring induced by maternal transfer of PBDE congeners in the commercial mixture DE-71 |
title_sort | persistent autism-relevant behavioral phenotype and social neuropeptide alterations in female mice offspring induced by maternal transfer of pbde congeners in the commercial mixture de-71 |
topic | Developmental Toxicology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8536480/ https://www.ncbi.nlm.nih.gov/pubmed/34687351 http://dx.doi.org/10.1007/s00204-021-03163-4 |
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