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1-溴丙烷（1-bp）的影响（1-bp），替代氯氟化合物对中枢神经系统（CNS）功能的影响。我们发现，使用Xenopus卵母细胞表达系统的实验中，我们发现1-bp可能直接抑制了GABA_A受体的功能，但分别抑制了神经元烟碱乙酰胆碱受体。 1-bp还增强了研究中使用大鼠海马切片制剂的研究中对种群尖峰（PPI）的配对脉冲抑制（PPI），这表明1 bp的麻醉作用。然而，当大鼠下次降低1 bp蒸气时，海马体中观察到的PS放大器的PPI降低，即与上述1-bp的直接效应相反，在海马中观察到，这种抑制作用在齿状回合中比CA1更重要。 RT-PCR分析表明，在1 bp暴露的大鼠的海马中，GABA_A受体β3和δ亚基的mRNA水平降低了 - 外突触GABA_A受体的成分。此外，体外和体内实验均表明1 bp改变了BDNF的mRNA水平，一种神经营养因子和抗凋亡分子BCl-XL，这可能是由于CREB和NF-κB激活的抑制作用。这些结果表明，1 bp可以通过不同的机制改变神经元令人兴奋，这需要进一步的投资才能澄清。另一方面，我们检查了从1 bp暴露的大鼠获得的大脑中的溴化物（BR-）浓度，以确定一种由1 bp inthalation造成的BR核心变化的一种障碍模型。结果，该模型以及我们的实验观察结果将描述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/或尿液样品中的BR浓缩将是1 bp吸入的有用的化学剂。

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