Executive Function Deficits and Social-Behavioral Abnormality in Mice Exposed to a Low Dose of Dioxin In Utero and via Lactation

Toshihiro Endo, Masaki Kakeyama, Yukari Uemura, Asahi Haijima, Hiroyuki Okuno, Haruhiko Bito, Chiharu Tohyama

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

An increasing prevalence of mental health problems has been partly ascribed to abnormal brain development that is induced upon exposure to environmental chemicals. However, it has been extremely difficult to detect and assess such causality particularly at low exposure levels. To address this question, we here investigated higher brain function in mice exposed to dioxin in utero and via lactation by using our recently developed automated behavioral flexibility test and immunohistochemistry of neuronal activation markers Arc, at the 14 brain areas. Pregnant C57BL/6 mice were given orally a low dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at a dose of either 0, 0.6 or 3.0 μg/kg on gestation day 12.5. When the pups reached adulthood, they were group-housed in IntelliCage to assess their behavior. As a result, the offspring born to dams exposed to 0.6 μg TCDD/kg were shown to have behavioral inflexibility, compulsive repetitive behavior, and dramatically lowered competitive dominance. In these mice, immunohistochemistry of Arc exhibited the signs of hypoactivation of the medial prefrontal cortex (mPFC) and hyperactivation of the amygdala. Intriguingly, mice exposed to 3.0 μg/kg were hardly affected in both the behavioral and neuronal activation indices, indicating that the robust, non-monotonic dose-response relationship. In conclusion, this study showed for the first time that perinatal exposure to a low dose of TCDD in mice develops executive function deficits and social behavioral abnormality accompanied with the signs of imbalanced mPFC-amygdala activation.

Original languageEnglish
Article numbere50741
JournalPLoS One
Volume7
Issue number12
DOIs
Publication statusPublished - 2012 Dec 12
Externally publishedYes

Fingerprint

Dioxins
dioxins
Executive Function
Lactation
Brain
tetrachlorodibenzo-p-dioxin
lactation
Chemical activation
mice
dosage
Amygdala
Prefrontal Cortex
amygdala
brain
Immunohistochemistry
immunohistochemistry
Compulsive Behavior
Medical problems
Dams
Environmental Exposure

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Executive Function Deficits and Social-Behavioral Abnormality in Mice Exposed to a Low Dose of Dioxin In Utero and via Lactation. / Endo, Toshihiro; Kakeyama, Masaki; Uemura, Yukari; Haijima, Asahi; Okuno, Hiroyuki; Bito, Haruhiko; Tohyama, Chiharu.

In: PLoS One, Vol. 7, No. 12, e50741, 12.12.2012.

Research output: Contribution to journalArticle

Endo, Toshihiro ; Kakeyama, Masaki ; Uemura, Yukari ; Haijima, Asahi ; Okuno, Hiroyuki ; Bito, Haruhiko ; Tohyama, Chiharu. / Executive Function Deficits and Social-Behavioral Abnormality in Mice Exposed to a Low Dose of Dioxin In Utero and via Lactation. In: PLoS One. 2012 ; Vol. 7, No. 12.
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