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.

我们通过1-溴丙烷（1-bp）研究了海马行为表现（1500ppm 6小时/天，5天/W，3周； 700pm，6小时/天/天，5天/w，12周）。我们在海马Slisses中分析了3周的暴露，分析了田间电位和LTP印刷刺激（IBS）空气我们发现1）降低了配对的脉冲渗透率，2）IBS诱导的LTP抑制3）CAMKII INCA1的活性降低，4）4）ca3 camkIIα和β的活性增加，Ca3和5 ）Phology既要染成Calbindin，GAD67，GAD65和GAT-1。在1500ppm的情况下，这些变化在4周的清除率上恢复了，在对照和1-bp大鼠之间，TBS诱导的LTP没有差异。 n尿液1 bp大鼠。海马。较低浓度的200和400ppm shoude的效果将来研究了。