title: Prenatal Exposure to Arsenic Impairs Behavioral Flexibility and Cortical Structure in Mice.
abstract: 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 (NaAsO2) suppresses neurite outgrowth of cortical neurons in vitro, it is largely unknown how developmental exposure to NaAsO2 impairs higher brain function and affects cortical histology. Here, we investigated the effect of prenatal NaAsO2 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 NaAsO2 (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 NaAsO2 displayed an impaired adaptation to repetitive reversal tasks. In morphometrical analyses of Nissl- or Golgi-stained tissue sections, we found that NaAsO2 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 NaAsO2 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 NaAsO2 leads to behavioral inflexibility in adulthood and cortical disarrangement in the PrL might contribute to this behavioral impairment.
authors.affiliation: Division of Life Science, Saitama UniversitySaitama, Japan; Department of Pharmacology, National Research Institute for Child Health and DevelopmentSetagaya, Japan.
authors.forename: Kyaw H
authors.initials: KH
authors.lastname: Aung
authors.affiliation: Division of Life Science, Saitama University Saitama, Japan.
authors.forename: Chaw
authors.initials: C
authors.lastname: Kyi-Tha-Thu
authors.affiliation: Molecular Toxicology Section, National Institute for Environmental Studies Tsukuba, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sano
authors.affiliation: Department of Pharmacology, National Research Institute for Child Health and Development Setagaya, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Department of Pharmacology, National Research Institute for Child Health and Development Setagaya, Japan.
authors.forename: Akito
authors.initials: A
authors.lastname: Tanoue
authors.affiliation: Molecular Toxicology Section, National Institute for Environmental Studies Tsukuba, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Nohara
authors.affiliation: Faculty of Human Sciences, Waseda University Tokorozawa, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Kakeyama
authors.affiliation: Faculty of Medicine, University of Tsukuba Tsukuba, Japan.
authors.forename: Chiharu
authors.initials: C
authors.lastname: Tohyama
authors.affiliation: Division of Life Science, Saitama University Saitama, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Tsukahara
authors.affiliation: Molecular Toxicology Section, National Institute for Environmental Studies Tsukuba, Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Maekawa
keywords: behavioral impairment; developmental neurotoxicity; neurite outgrowth; prelimbic cortex; sodium arsenite