Distribution of Exposed Organic Solvent in the Brain and its Effect on GABA_A Receptor
| Project/Area Number |
12670356
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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 |
Public health/Health science
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| Research Institution | OKAYAMA UNIVERSITY |
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Principal Investigator |
ITO Takehiko Okayama University, Faculty of Education, Associate Professor, 教育学部, 助教授 (10291973)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | organic solvent intoxication / m-xylene / GABA recptors / autoradiography / inhalation experiments / industrial health / Ro15-4513 / ベンゾジアゼピン結合部位 |
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| Research Abstract |
1. Establishment of a new system for exposing organic solvents to small animals
A system suitable for exposing m-xylene to rats was made, and a series of experiments was conducted using this system. The exposure system was easy to handle, and was useful.
2. Effects of m-xylene exposure on GABA_A receptor in the brain
Autoradiographic study was done using three ligands specific to GABA_A receptors. Autoradiography using [^<35>S]t-butylbicyclophosphorothionate revealed a significant increase in the binding in the cerebellum, whereas that using [^3H]flunitrazepam showed no significant changes. To further investigate the possibility of a receptor subunit-specific effect of m-xylene, autoradiogram using [^3H]Ro15-4513 was obtained. Significant changes in binding were found in the II-IIIth layer of the cerebral cortex, CA1, Inferior colliculus and in the granule cells of the cerebellum. The increase in the binding in the granule cells seemed to be a subunit-specific change, possibly due to alteration in alpha6 subunit-containing receptors.
3. Measurement of m-xylene concentration in several areas of the brain
The levels of m-xylene on and after the exposure were measured, and referenced with its metabolite concentration in urine.
4. Measurement of m-methylhippuric acid in urine on and after the exposure
The levels of m-methylhippuric acid were measured on and after the exposure. While m-xylene level and m-methylhippuric acid level paralleled during the exposure, the two levels decreased in a different manner after the exposure.
These findings taken together, the basic data to develop a new biological effect monitoring of m-xylene were obtained. The new biological monitoring method will use changes in GABA_A receptor as indices of biological effect, and metabolite of m-xylene in urine (m-methylhippuric acid and/or its precursor m-tolualdehyde) as indices of the exposure, respectively.
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Report
(3 results)
Research Products
(4 results)
