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Brain slice techniques as neurotoxicity tests for 1-bromopropane

脑切片技术作为 1-溴丙烷的神经毒性测试

基本信息

批准号：
12680556
负责人：
FUETA Yukiko
金额：
$ 2.18万
依托单位：
University of Occupational and Environmental Health
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12680556/
关键词：
1-bromopropane neurotoxitity brain slice GABAergic inhibition LTP immunohistochemistry signal transduction 神経毒性

项目摘要

We studied hippocampal toxicity before behavioral manifestations induced by 1-bromopropane (1-BP). Wistar male rats were exposed to 1-BP by inhalation (1500ppm 6 hrs/day, 5 days/w, 3 weeks ; 700ppm, 6 hrs/day, 5 days/w, 12 weeks).After the end of the 3-week exposure, we analysed paired-pulse ratios of field potential and LTP induced by theta-burst-stimulation (IBS) in hippocampal slices. Biochemical analysis of CaMK II α, β, MARK and synapsin I, and immunohistochemical examinations were performed on the hippocampus. They were compared to those of control rats exposed to room air We found that 1) the paired-pulse inhibition was reduced, 2) IBS-induced LTP was suppressed 3) decrease in activity of CaMKII β in CA1, 4) increase in synapsin I, activity of CaMK II α and β in CA3, and 5) there was no change in cell morphology either principal or non-principal GABAergic) neurones stained by calbindin, GAD67, GAD65 and GAT-1.In 700ppm inhalation, we also observed disinihbition in both CA1 and DG from 4 week-inhalation. Changes in signal transduction at 12 week was similar to those obtained at 1500ppm. These changes were recovered at 4 week clearance after 12week inhalation There was no difference in TBS-induced LTP between control ande1-BP rats. As a metabolic product we found grycidol in urin of 1-BP rats. Since grycidol is known to be neurotoxic the effects might result from action of grycidol.It is concluded that subchronic and chronic exposure to 1-BP caused hyperexcitability of hippocampus and impairment of synaptic plasticity, suggesting functional changes in the hippocampus.The effects at lower concentration of 200 and 400ppm should be studied in future.

我们研究了1-溴丙烷（1-BP）诱导的行为表现之前的海马毒性。雄性Wistar大鼠吸入1-BP（1500 ppm，6 h/d，5d/w，3周; 700 ppm，6 h/d，5d/w，12周），3周后观察海马脑片场电位的双脉冲比值和θ-爆发刺激（IBS）诱发的LTP。对海马进行CaMK II α、β、MARK和突触蛋白I的生化分析和免疫组织化学检查。结果发现：1）双脉冲抑制减少，2）IBS诱导的LTP被抑制，3）CA 1区CaMK Ⅱ β活性降低，4）CA 3区突触蛋白I、CaMK Ⅱ α和β活性增加，5）钙结合蛋白、GAD 67、GAD-65和GAT-1。吸入700 ppm，从4周开始，我们也观察到CA_1和DG的消除。12周时信号转导的变化与1500 ppm相似。吸入12周后，这些变化在4周清除时恢复。对照组和1-BP组大鼠的LTP无差异。在1-BP大鼠尿中发现了代谢产物grycidol。结论：1-BP亚慢性和慢性染毒可引起海马兴奋性增高和突触可塑性损害，提示海马功能改变，低浓度（200和400 ppm）的影响有待进一步研究。