Brain serotonin system disorder induced by in utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin in rat.
| Project/Area Number |
13833006
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
放射線・化学物質影響科学
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| Research Institution | Kagoshima University |
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Principal Investigator |
KUCHIIWA Satoshi Kagoshima University, Graduate School of Medical and Dental Sciences, associate professor, 大学院・医歯学総合研究所, 助教授 (90161637)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2003: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2002: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2001: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | dioxin toxicity / serotonin immunoreactivity / enkephalin / immunohistochemistry / nitric oxide / neurotransmitter disorder / endocrine disruptor / encephalopathy / 神経伝達物質 / 環境かく乱化学物質 / 行動異常 / 神経毒性 / 神経化学的影響 / 胎盤母乳暴露 / 内分泌かくらん化学物質 |
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| Research Abstract |
1.Female ddY mice were administered 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) by gavage. In the breast-fed offspring born to the TCDD-exposed mice at 42 days of age, a marked decrease in intensity of serotonin immunostaining occurred in all raphe nuclei compared with the control offspring. In utero and/or lactational TODD exposure causes a long-lasting change in the serotonergic system in the raphe nuclei of offspring.
2.After a single administration of TODD to the adult Long-Evans rat, a significantly large number of Fos-immunoreactive cells were found in the hypothalamus, amygdaloid nucleus and bed nucleus of the stria terminalis. It is suggested that these areas play an important role in TCDD-induced anorexia and progressive body weight loss.
3.After a single administration of TCDD to the rats, neuronal nitric oxide synthase (nNOS) Western blotting experiment indicated marked decrease in nNOS immunoreactivity in the brain. NADPH-diaphorase histochemistry showed a marked decrease in the number of positive cells in the hypothalamus. The results suggest that TODD down-regulates nitric oxide product in the hypothalamus, which may be partially responsible for TODD-induced feeding inhibition.
4.After TODD gastric administration to the rat, a marked increase in the density of methionine-enkephalin immunoreactive cell bodies, fibers and terminals was found in the forebrain. All these results suggest that some TODD toxicity may be induced by its direct action on the central nervous system.
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Report
(4 results)
Research Products
(17 results)
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[Publications] Kuchiiwa, S., Cheng.S-B., Nagatomo, I., Akasaki, Y., Uchida, M., Tominaga, M., Hashiguchi, W., Kuchiiwa, T.: "In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin decreases serotonin-immunoreactive neurons in raphe nuclei of male mouse offspring"Neuroscience Letters. 317. 73-76 (2002)
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[Publications] Cheng, S., Kuchiiwa, S., Nagatomo, I., Akasaki, Y., Uchida, M., Tominaga, M., Hashiguchi, W., Kuchiiwa, T., Nakagawa, S.: "2,3,7,8-Tetrachlorodibenzo-p-dioxin treatment induces c-fos expression in the forebrain of the Long-Evans rat"Brain Research. (In Press).
