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Effects of neonatal exposure to tributyltin on the rat brain myelination.

新生儿接触三丁基锡对大鼠脑髓鞘形成的影响。

基本信息

批准号：
16510043
负责人：
KOJIMA Hisako
金额：
$ 2.11万
依托单位：
Kitasato University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

项目摘要

Tributyltin (TBT) is recognized as an endocrine-disrupting chemical, because of suppressing the aromatase for conversion of androgen to estrogen. The purpose of this study was to evaluate the effect of TBT on development of rat neuronal tissues.A: Prenatal exposure to TBT(1) Pregnant rats were exposed TBT on days 7 or 14 of pregnancy. The offspring brains were collected on the 21st day after birth. Steroid contents, P450 activity in microsome fractions, and the activities of oligodendrocyte enzyme CNP (2', 3'-cyclic nucleotide 3'-phosphodiesterase) in the TBT exposed rats were not significantly different from those in the control rats. Results showed that prenatal exposure to TBT did not affect the brain development of offspring. The fetuses are probably defended from TBT by the placenta.B: Neonatal exposure to TBT(1) Neonatal rats were exposed TBT on the day of birth. Brains of offspring were collected on 21, 35, and 49 days of age. The CNP activities of myelin in all neonatal TBT exposed groups were significantly decreased compared with those of the control groups even in the relatively low level exposure. Western blot analysis of CNP showed the similar results as enzyme activities at each developmental stage. (2) The mRNA levels of major brain myelin proteins of TBT-exposed rats were selectively affected compared with the levels of control rats. (3) The mRNA levels of glycolipid synthesis glycosyltransferases in the brains of TBT-exposed rats were almost same as the levels of control rats. However, the levels of GlcCer synthase and CSE synthase (sulfatide synthase) of TBT-exposed rat brain at 7 weeks of age were remarkably decreased compared with the levels of control rats. (4) TLC profiles of sphingoglycolipids and phospholipids in the brains of TBT-exposed and control rats were examined. (289 words)

三丁基锡（TBT）被认为是一种内分泌干扰化学物质，因为它可以抑制雄激素向雌激素转化的芳香化酶。本研究旨在探讨TBT对大鼠神经组织发育的影响。A：产前暴露于TBT(1)怀孕大鼠在怀孕第7天或第14天暴露于TBT。在出生后第21天采集子代脑。TBT暴露大鼠体内类固醇含量、微粒体P450活性和少突胶质细胞酶CNP（2′，3′-环核苷酸3′-磷酸二酯酶）活性与对照组无显著差异。结果表明，产前接触TBT对后代的大脑发育没有影响。胎盘可能保护胎儿免受TBT的侵害。B：新生大鼠暴露于TBT(1)新生大鼠在出生当天暴露于TBT。分别于21日龄、35日龄和49日龄采集子代脑。所有新生儿TBT暴露组的髓磷脂CNP活性均显著低于对照组，即使暴露水平相对较低。Western blot分析结果显示，CNP在各发育阶段的酶活性相似。(2)与对照组相比，tbt暴露大鼠脑髓磷脂主要蛋白mRNA水平受到选择性影响。(3) tbt暴露大鼠脑内糖脂合成糖基转移酶mRNA水平与对照组基本相同。然而，与对照组相比，tbt暴露大鼠7周龄脑glcer合成酶和CSE合成酶（硫脂合成酶）水平显著降低。(4)检测了tbt暴露大鼠和对照组大鼠脑内鞘糖脂和磷脂的TLC谱。(289字)