Fueta Yukiko, Fukunaga Kohji, Ishidao Toru, Hori Hajime
The First Department of Medical Technology, School of Health Sciences, University of Occupational and Environmental Health, Iseigaoka 1-1, Yahatanishi-ku, 807-8555, Kitakyushu, Japan.
Life Sci. 2002 Dec 20;72(4-5):521-9. doi: 10.1016/s0024-3205(02)02247-6.
Chronic inhalation of 1-bromopropane (1-BP), a substitute of ozone-depleting chlorofluorocarbons, has been suspected of having central neurotoxicity (Clinical Neurology and Neurosurgery 101 (1999) 199; Journal of Occupational Health 44 (2002) 1) for humans. In animal experiments, 1-BP inhalation (1500 ppm) caused hyperexcitability in the CA1 and the dentate gyrus (DG) [Journal of Occupational Health 42 (2000) 149, Journal of Occupational Health 44 (2002) 156]. We studied whether the hyperexcitability is associated with changes of Ca2+/calmodulin-dependent kinase II (CaMKII), mitogen-activated protein kinase (MAPK), and protein kinase C (PKC). Male Wistar rats were exposed to 1-BP for 6 hours in a day in an exposure chamber with a concentration of 700 ppm for 8 weeks. After the inhalation, paired-pulse ratios of field excitatory postsynaptic potentials and population spikes (PSs) were analyzed in the CA1 and DG of hippocampal slices. Control rats were then given fresh air in the inhalation chamber. Semiquantitative immunoblotting analyses of protein kinases using antibodies against active and conventional protein kinases were done using the whole hippocampus. A paired-pulse ratio of PS was increased at the 5 ms interpulse interval in the CA1 and at the 10-20 ms interpulse intervals in the DG. The amount of active MAPK and total amount of CaMKIIalpha and beta were significantly increased by 28, 29, and 46% compared to control, respectively, without any change in PKC activity. In contrast, the amount of active CaMKIIbeta was decreased to 78%. These results suggest that modifications of intracellular signaling cascades are associated with hyperexcitability that occurred in the hippocampal formation of rats exposed to the chronic inhalation of 1-BP.
长期吸入1-溴丙烷（1-BP），一种消耗臭氧层的氯氟烃的替代品，被怀疑对人类具有中枢神经毒性（《临床神经病学与神经外科》101（1999）199；《职业健康杂志》44（2002）1）。在动物实验中，吸入1-BP（1500 ppm）会导致海马体CA1区和齿状回（DG）出现过度兴奋[《职业健康杂志》42（2000）149，《职业健康杂志》44（2002）156]。我们研究了这种过度兴奋是否与钙/钙调蛋白依赖性激酶II（CaMKII）、丝裂原活化蛋白激酶（MAPK）和蛋白激酶C（PKC）的变化有关。雄性Wistar大鼠在浓度为700 ppm的暴露舱中每天暴露于1-BP 6小时，持续8周。吸入后，在海马切片的CA1区和DG区分析场兴奋性突触后电位和群体峰电位（PSs）的配对脉冲比率。然后在吸入舱中给对照大鼠提供新鲜空气。使用针对活性和传统蛋白激酶的抗体，对整个海马体进行蛋白激酶的半定量免疫印迹分析。在CA1区，当脉冲间隔为5 ms时，PS的配对脉冲比率增加；在DG区，当脉冲间隔为10 - 20 ms时，PS的配对脉冲比率增加。与对照组相比，活性MAPK的量以及CaMKIIα和β的总量分别显著增加了28%、29%和46%，而PKC活性没有任何变化。相反，活性CaMKIIβ的量减少到了78%。这些结果表明，细胞内信号级联反应的改变与长期吸入1-BP的大鼠海马结构中出现的过度兴奋有关。
