Studies on the pleiotropic effects of gaseous chemical compound on the function of the central nervous system.

研究气态化合物对中枢神经系统功能的多效性影响。

• 批准号: 16590214
• 负责人: UENO Susumu
• 金额: $ 2.3万
• 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: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590214/
• 关键词: gaseous chemical compound; 1-bromopropane; GABA_A receptor; Xenopus oocytes; hippocampal slice; disinhibition; δ subunit; BDNF; 反回抑制; 脳由来神経栄養因子; 培養神経細胞

In this research, we investigated the effects of 1-bromopropane (1-BP), a substitute for chlorofluorocarbons, on the function of the central nervous system (CNS). We found that 1-BP directly potentiated the function of GABA_A receptors, but inhibited neuronal nicotinic acetylcholine receptors, respectively, from the experiments using Xenopus oocytes expression system. 1-BP also enhanced paired-pulse inhibition (PPI) of population spike (PS) amplitudes in the study using rat hippocampal slice preparations, suggesting an anesthetic effect of 1-BP. However, when the rats were exposed to 1-BP vapor subchronically, the decrease in PPI of PS amplitudes, i.e.disinhibition which was opposite to the direct effect of 1-BP mentioned above, was observed in the hippocampus, and this disinhibition occurred in the dentate gyrus more predominantly than CA1 area. RT-PCR analysis indicated decreased mRNA levels of GABA_A receptor β3 and δ subunits - the components of extrasynaptic GABA_A receptors - in the hippocampus of 1-BP-exposed rats. Moreover, both in vitro and in vivo experiments revealed that 1-BP altered mRNA levels of BDNF, a neurotrophic factor and Bcl-xL, an anti-apoptotic molecule, which was probably due to the inhibition of CREB and NF-κB activation, respectively. These results demonstrate that 1-BP may alter neuronal excitability via different mechanisms, which requires further investigation to be clarified.On the other hand, we examined bromide (Br-) concentrations in the brain obtained from 1-BP-exposed rats, to determine the one compartment model for time-dependent changes of Br- concentrations caused by 1-BP inhalation. In consequence, this model, together with our experimental observations, would describe a risk assessment for the CNS neurotoxicity induced by 1-BP exposure, which also suggests that Br- concentration in the blood and/or urine sample would be a useful chemical-indicator of 1-BP inhalation.

在这项研究中，我们研究了氯氟烃替代品 1-溴丙烷 (1-BP) 对中枢神经系统 (CNS) 功能的影响，我们发现 1-BP 直接增强 GABA_A 受体的功能。使用非洲爪蟾卵母细胞表达系统的实验分别抑制神经元烟碱乙酰胆碱受体，还增强了群体尖峰的配对脉冲抑制（PPI）。在使用大鼠海马切片制剂的研究中，发现了 1-BP 的麻醉作用，然而，当大鼠亚慢性暴露于 1-BP 蒸气时，PS 振幅的 PPI 降低，即去抑制作用。上述 1-BP 的直接作用是在海马中观察到的，这种去抑制作用比 CA1 区域更主要发生在 mRNA 水平上。暴露于 1-BP 的大鼠海马中 GABA_A 受体 β3 和 δ 亚基（突触外 GABA_A 受体的组成部分）的变化此外，体外和体内实验均表明 1-BP 改变了 BDNF（一种神经营养因子）的 mRNA 水平。 Bcl-xL 是一种抗凋亡分子，这可能是分别抑制 CREB ​​和 NF-κB 的激活。这些结果表明。 1-BP可能通过不同的机制改变神经元的兴奋性，这需要进一步的研究来阐明。另一方面，我们检查了从1-BP暴露的大鼠大脑中获得的溴化物（Br-）浓度，以确定单室模型因此，该模型与我们的实验观察一起，可以描述 1-BP 暴露引起的中枢神经系统神经毒性的风险评估，这也表明：血液和/或尿液样本中的 Br 浓度将是 1-BP 吸入的有用化学指示剂。

项目成果

Changes in the function of the inhibitory neurotransmitter system following subchronic inhalation exposure to 1-bromopropane.

亚慢性吸入暴露于 1-溴丙烷后抑制性神经递质系统功能的变化。

• 期刊: Neuro Toxicology (印刷中)
• 作者: Ueno S.;et al.
• 通讯作者: et al.

大学における室内環境中のVOC濃度

大学室内环境VOC浓度

• 发表时间: 2004
• 期刊: 作業環境 25(5)
• 作者: Tanaka N.;Nejime N.;Kagota S.;Kubota Y.;Nakamura K.;Kunitomo M.;Hashimoto M.;Yamamoto R.;Shinozuka K.;石田尾 徹 他
• 通讯作者: 石田尾 徹 他