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Prenatal Exposure to Arsenic Impairs Behavioral Flexibility and Cortical Structure in Mice

Exposure to arsenic from well water in developing countries is suspected to cause developmental neurotoxicity. Although, it has been demonstrated that exposure to sodium arsenite (NaAsO(2)) suppresses neurite outgrowth of cortical neurons in vitro, it is largely unknown how developmental exposure to...

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Autores principales: Aung, Kyaw H., Kyi-Tha-Thu, Chaw, Sano, Kazuhiro, Nakamura, Kazuaki, Tanoue, Akito, Nohara, Keiko, Kakeyama, Masaki, Tohyama, Chiharu, Tsukahara, Shinji, Maekawa, Fumihiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2016
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4814721/
https://www.ncbi.nlm.nih.gov/pubmed/27064386
http://dx.doi.org/10.3389/fnins.2016.00137
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author Aung, Kyaw H.
Kyi-Tha-Thu, Chaw
Sano, Kazuhiro
Nakamura, Kazuaki
Tanoue, Akito
Nohara, Keiko
Kakeyama, Masaki
Tohyama, Chiharu
Tsukahara, Shinji
Maekawa, Fumihiko
author_facet Aung, Kyaw H.
Kyi-Tha-Thu, Chaw
Sano, Kazuhiro
Nakamura, Kazuaki
Tanoue, Akito
Nohara, Keiko
Kakeyama, Masaki
Tohyama, Chiharu
Tsukahara, Shinji
Maekawa, Fumihiko
author_sort Aung, Kyaw H.
collection PubMed
description Exposure to arsenic from well water in developing countries is suspected to cause developmental neurotoxicity. Although, it has been demonstrated that exposure to sodium arsenite (NaAsO(2)) suppresses neurite outgrowth of cortical neurons in vitro, it is largely unknown how developmental exposure to NaAsO(2) impairs higher brain function and affects cortical histology. Here, we investigated the effect of prenatal NaAsO(2) exposure on the behavior of mice in adulthood, and evaluated histological changes in the prelimbic cortex (PrL), which is a part of the medial prefrontal cortex that is critically involved in cognition. Drinking water with or without NaAsO(2) (85 ppm) was provided to pregnant C3H mice from gestational days 8 to 18, and offspring of both sexes were subjected to cognitive behavioral analyses at 60 weeks of age. The brains of female offspring were subsequently harvested and used for morphometrical analyses. We found that both male and female mice prenatally exposed to NaAsO(2) displayed an impaired adaptation to repetitive reversal tasks. In morphometrical analyses of Nissl- or Golgi-stained tissue sections, we found that NaAsO(2) exposure was associated with a significant increase in the number of pyramidal neurons in layers V and VI of the PrL, but not other layers of the PrL. More strikingly, prenatal NaAsO(2) exposure was associated with a significant decrease in neurite length but not dendrite spine density in all layers of the PrL. Taken together, our results indicate that prenatal exposure to NaAsO(2) leads to behavioral inflexibility in adulthood and cortical disarrangement in the PrL might contribute to this behavioral impairment.
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spelling pubmed-48147212016-04-08 Prenatal Exposure to Arsenic Impairs Behavioral Flexibility and Cortical Structure in Mice Aung, Kyaw H. Kyi-Tha-Thu, Chaw Sano, Kazuhiro Nakamura, Kazuaki Tanoue, Akito Nohara, Keiko Kakeyama, Masaki Tohyama, Chiharu Tsukahara, Shinji Maekawa, Fumihiko Front Neurosci Endocrinology Exposure to arsenic from well water in developing countries is suspected to cause developmental neurotoxicity. Although, it has been demonstrated that exposure to sodium arsenite (NaAsO(2)) suppresses neurite outgrowth of cortical neurons in vitro, it is largely unknown how developmental exposure to NaAsO(2) impairs higher brain function and affects cortical histology. Here, we investigated the effect of prenatal NaAsO(2) exposure on the behavior of mice in adulthood, and evaluated histological changes in the prelimbic cortex (PrL), which is a part of the medial prefrontal cortex that is critically involved in cognition. Drinking water with or without NaAsO(2) (85 ppm) was provided to pregnant C3H mice from gestational days 8 to 18, and offspring of both sexes were subjected to cognitive behavioral analyses at 60 weeks of age. The brains of female offspring were subsequently harvested and used for morphometrical analyses. We found that both male and female mice prenatally exposed to NaAsO(2) displayed an impaired adaptation to repetitive reversal tasks. In morphometrical analyses of Nissl- or Golgi-stained tissue sections, we found that NaAsO(2) exposure was associated with a significant increase in the number of pyramidal neurons in layers V and VI of the PrL, but not other layers of the PrL. More strikingly, prenatal NaAsO(2) exposure was associated with a significant decrease in neurite length but not dendrite spine density in all layers of the PrL. Taken together, our results indicate that prenatal exposure to NaAsO(2) leads to behavioral inflexibility in adulthood and cortical disarrangement in the PrL might contribute to this behavioral impairment. Frontiers Media S.A. 2016-03-31 /pmc/articles/PMC4814721/ /pubmed/27064386 http://dx.doi.org/10.3389/fnins.2016.00137 Text en Copyright © 2016 Aung, Kyi-Tha-Thu, Sano, Nakamura, Tanoue, Nohara, Kakeyama, Tohyama, Tsukahara and Maekawa. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Aung, Kyaw H.
Kyi-Tha-Thu, Chaw
Sano, Kazuhiro
Nakamura, Kazuaki
Tanoue, Akito
Nohara, Keiko
Kakeyama, Masaki
Tohyama, Chiharu
Tsukahara, Shinji
Maekawa, Fumihiko
Prenatal Exposure to Arsenic Impairs Behavioral Flexibility and Cortical Structure in Mice
title Prenatal Exposure to Arsenic Impairs Behavioral Flexibility and Cortical Structure in Mice
title_full Prenatal Exposure to Arsenic Impairs Behavioral Flexibility and Cortical Structure in Mice
title_fullStr Prenatal Exposure to Arsenic Impairs Behavioral Flexibility and Cortical Structure in Mice
title_full_unstemmed Prenatal Exposure to Arsenic Impairs Behavioral Flexibility and Cortical Structure in Mice
title_short Prenatal Exposure to Arsenic Impairs Behavioral Flexibility and Cortical Structure in Mice
title_sort prenatal exposure to arsenic impairs behavioral flexibility and cortical structure in mice
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4814721/
https://www.ncbi.nlm.nih.gov/pubmed/27064386
http://dx.doi.org/10.3389/fnins.2016.00137
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