2001 Fiscal Year Final Research Report Summary
Brain slice techniques as neurotoxicity tests for 1-bromopropane
| Project/Area Number |
12680556
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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 |
環境影響評価(含放射線生物学)
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| Research Institution | University of Occupational and Environmental Health |
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Principal Investigator |
FUETA Yukiko University of Occupational and Environmental Health, School of Health Science, Resarch Associate, 産業保健学部, 助手 (10132482)
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| Co-Investigator(Kenkyū-buntansha) |
FUKUNAGA Kohji Kumamoto University, School of Medicine, Associate Professor, 医学部, 助教授 (90136721)
NATSUME Kiyohisa Graduate School of Kyushu Institute of Tachnology, Graduate School of Life Science and Systems Engineering. Associate Professor, 大学院・生命体工学研究科, 助教授 (30231492)
HORI Hajime University of Occupational and Environmental Health, School of Health Science, professor, 産業保健学部, 教授 (70140902)
FUKUDA Takaichi Kyushu University, Graduate School of Medical Sciences, Assistant professor, 大学院・医学系研究科, 講師 (50253414)
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| Project Period (FY) |
2000 – 2001
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| Keywords | 1-bromopropane / neurotoxitity / brain slice / GABAergic inhibition / LTP / immunohistochemistry / signal transduction |
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| Research Abstract |
We studied hippocampal toxicity before behavioral manifestations induced by 1-bromopropane (1-BP). Wistar male rats were exposed to 1-BP by inhalation (1500ppm 6 hrs/day, 5 days/w, 3 weeks ; 700ppm, 6 hrs/day, 5 days/w, 12 weeks).
After the end of the 3-week exposure, we analysed paired-pulse ratios of field potential and LTP induced by theta-burst-stimulation (IBS) in hippocampal slices. Biochemical analysis of CaMK II α, β, MARK and synapsin I, and immunohistochemical examinations were performed on the hippocampus. They were compared to those of control rats exposed to room air We found that 1) the paired-pulse inhibition was reduced, 2) IBS-induced LTP was suppressed 3) decrease in activity of CaMKII β in CA1, 4) increase in synapsin I, activity of CaMK II α and β in CA3, and 5) there was no change in cell morphology either principal or non-principal GABAergic) neurones stained by calbindin, GAD67, GAD65 and GAT-1.
In 700ppm inhalation, we also observed disinihbition in both CA1 and DG from 4 week-inhalation. Changes in signal transduction at 12 week was similar to those obtained at 1500ppm. These changes were recovered at 4 week clearance after 12week inhalation There was no difference in TBS-induced LTP between control ande1-BP rats. As a metabolic product we found grycidol in urin of 1-BP rats. Since grycidol is known to be neurotoxic the effects might result from action of grycidol.
It is concluded that subchronic and chronic exposure to 1-BP caused hyperexcitability of hippocampus and impairment of synaptic plasticity, suggesting functional changes in the hippocampus.
The effects at lower concentration of 200 and 400ppm should be studied in future.
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Research Products
(6 results)
