2005 Fiscal Year Final Research Report Summary
Studies on the pleiotropic effects of gaseous chemical compound on the function of the central nervous system.
| Project/Area Number |
16590214
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | University of Occupational and Environmental Health |
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Principal Investigator |
UENO Susumu University of Occupational and Environmental Health, School of Medicine, Assistant Professor, 医学部, 講師 (00279324)
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| Co-Investigator(Kenkyū-buntansha) |
FUETA Yukiko University of Occupational and Environmental Health, School of Health Sciences, Research Associate, 産業保健学部, 助手 (10132482)
YOSHIDA Yasuhiro University of Occupational and Environmental Health, School of Medicine, Assistant Professor, 医学部, 講師 (10309958)
ISHIDAO Toru University of Occupational and Environmental Health, School of Health Sciences, Assistant Professor, 産業保健学部, 講師 (90212901)
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| Project Period (FY) |
2004 – 2005
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| Keywords | gaseous chemical compound / 1-bromopropane / GABA_A receptor / Xenopus oocytes / hippocampal slice / disinhibition / δ subunit / BDNF |
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| Research Abstract |
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.
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Research Products
(4 results)
