Changes in the function of the inhibitory neurotransmitter system in the rat brain following subchronic inhalation exposure to 1-bromopropane
详细信息 查看全文
- 作者：Susumu Ueno ; Yasuhiro Yoshida ; Yukiko Fueta ; Toru Ishidao ; Jiqin Liu ; Naoki Kunugita ; Nobuyuki Yanagihara ; Hajime Hori
- 关键词：1-Bromopropane ; GABAA receptor ; Xenopus oocytes ; δ ; Subunit ; Disinhibition
- 刊名：Neurotoxicology
- 出版年：2007
- 出版时间：March 2007
- 年：2007
- 卷：28
- 期：2
- 页码：415-420
- 全文大小：242 K
文摘
1-Bromopropane (1-BP) has been widely used as a cleaning agent and a solvent in industries, but the central neurotoxicity of 1-BP remains to be clarified. In the present study, we investigated the effects of subchronic inhalation exposure to 1-BP vapor on the function of the inhibitory neurotransmitter system mediated by γ-aminobutyric acid (GABA) in the rat brain. Male Wistar rats were exposed to 1-BP vapor for 12 weeks (6 h/day, 5 days/week) at a concentration of 400 ppm, and, in order to investigate the expression and function of brain GABA type A (GABAA) receptors, total/messenger RNA was prepared from the neocortex, hippocampus, and cerebellum of the control and 1-BP-exposed rats. Moreover, hippocampal slices were prepared, and the population spike (PS) amplitude and the slope of the field excitatory postsynaptic potential (fEPSP) were investigated in the paired-pulse configuration of the extracellular recording technique. Using the Xenopus oocyte expression system, we compared GABA concentration–response curves obtained from oocytes injected with brain subregional mRNAs of control and 1-BP exposed rats, and observed no significant differences in apparent GABA affinity. On the other hand, paired-pulse inhibition of PS amplitude was significantly decreased in the hippocampal dentate gyrus (DG) by exposure to 1-BP, without any effect on the paired-pulse ratio of the fEPSP slopes, suggesting neuronal disinhibition in the DG. Moreover, RT-PCR analysis indicated decreased levels of GABAA receptor β3 and δ subunit mRNAs in the hippocampus of 1-BP-exposed rats. These results demonstrate that subchronic inhalation exposure to 1-BP vapor reduces the function of the hippocampal GABAergic system, which could be due to changes in the expression and function of GABAA receptors, especially the δ subunit-containing GABAA receptors.