title: Alterations of neurotransmitter norepinephrine and gamma-aminobutyric acid correlate with murine behavioral perturbations related to bisphenol A exposure.
abstract: OBJECTIVE
  Humans are commonly exposed to endocrine-disrupting chemical bisphenol A (BPA), giving rise to concern over the psychobehavioral effects of BPA. The aim of this study was to investigate the effects of prenatal and lactational BPA exposure on neurotransmitters, including norepinephrine (NE), gamma-aminobutyric acid (GABA) and glutamate (Glu), and to assess the association with behavioral phenotypes.
  
  
  METHODS
  C57BL/6J mice were orally administered with BPA (500 μg/bwkg/day) or vehicle daily from embryonic day 0 to postnatal week 3 (P3W), through their dams. The IntelliCage behavioral experiments were conducted from P11W to P15W. At around P14-16W, NE, GABA and Glu levels in nine brain regions were measured by high performance liquid chromatography. Furthermore, the associations between the neurotransmitter levels and the behavioral indices were statistically analyzed.
  
  
  RESULTS
  In females exposed to BPA, the GABA and Glu levels in almost all regions, and the NE levels in the cortex, hypothalamus and thalamus were higher than those in the controls. In males exposed to BPA, the GABA levels in the amygdala and hippocampus showed lower values, while Glu levels were higher in some regions, compared with the controls. In regard to the associations, the number of "diurnal corner visits without drinking" was correlated with the NE levels in the cortex and thalamus in females. The "nocturnal corner visit duration without drinking" was correlated with the GABA level in the hippocampus in males.
  
  
  CONCLUSIONS
  These results suggest that prenatal and lactational exposure to low doses of BPA might modulate the NE, GABA and Glu systems, resulting in behavioral alterations.
authors.affiliation: Department of Pathology and Applied Neurobiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ogi
authors.affiliation: Department of Pathology and Applied Neurobiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. Electronic address: kxi14@koto.kpu-m.ac.jp.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Itoh
authors.affiliation: Department of Forensic Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ikegaya
authors.affiliation: Department of Pathology and Applied Neurobiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Fushiki
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001559:Benzhydryl Compounds / Q000633:toxicity*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D007774:Lactation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009638:Norepinephrine / Q000378:metabolism*; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D018698:Glutamic Acid; D009638:Norepinephrine; D010636:Phenols; D005680:gamma-Aminobutyric Acid; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Behavior; Bisphenol A; Development; IntelliCage; Neurotransmitter