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Subacute administration of tributyltin chloride modulates neurotransmitters and their metabolites in discrete brain regions of maternal mice and their F1 offspring

Department of Preventive Medicine and Public Health, Kitasato University School of Medicine, Kitasato 1-15-1, Sagamihara, Kanagawa 228-8555, Japan, mtsunoda{at}med.kitasato-u.ac.jp

Yoshiharu Aizawa

Department of Preventive Medicine and Public Health, Kitasato University School of Medicine, Kitasato 1-15-1, Sagamihara, Kanagawa 228-8555, Japan

Nobuhiro Konno

Koriyama Women’s University and College, Koriyama, Fukushima, Japan

Kimiko Kimura

Department of Veterinary Medicine, Azabu University, Sagamihara, Kanagawa, Japan

Yoshiko Sugita-Konishi

Division of Microbiology, National Institute of Health Sciences, Tokyo, Japan

Tributyltin (TBT) compounds have been used as anti-fouling agents and the central nervous system is one of its target organs. TBT-induced modulations of neurotransmitters in the brains of adult mice have been reported. However, little is known about the developmental neurotoxicity of TBT. In this study, we evaluated the effects of TBT on neurotransmitters and their metabolites in discrete brain regions of female ICR mice and their offspring. Pregnant ICR mice were exposed to TBT chloride at concentrations of 0, 15 or 50 ppm in water or 125 ppm in food. Male offspring were sacrificed at one, two and three weeks after birth. The concentrations of norepinephrine, dopamine (DA), dihydoxyphenylacetic acid, homovanillic acid (HVA), serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) were determined in different brain regions by HPLC. All offspring from the 125 ppm group died immediately after birth. A significant decrease in the body weight of the TBT-treated F1 groups compared to the control group was observed in the first week. Significant increases compared to the controls were observed for the DA concentration in the striatum of the 50 ppm F1 group, and for the HVA concentration in the cerebrum and the 5-HT concentration in the medulla oblongata of the 15 and 50 ppm F1 groups in the third week. At three weeks of age, the neurotransmitters and their metabolites may be useful indexes for developmental neurotoxicity. For the dams, a significant decrease in the 5-HT concentration was observed in the cerebellum, medulla, midbrain and striatum of the 125 ppm group compared to the control group. A significant decrease in the 5-HIAA concentration was also observed in the cerebellum, midbrain and striatum of the dams in the 125 ppm group compared to the control. TBT may induce a decrease in the synthesis of 5-HT in the dams. The discrepancy between dams and offspring may be due to several factors such as age, dose, route, sex and pregnancy.

Key Words: dam • F1 mice • 5-HT • mouse • neurotoxicity • tributyltin

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