2007 Fiscal Year Final Research Report Summary
Researches on the in vivo analyses of brain neurotransmitters in the animal model of schizophrenia
| Project/Area Number |
17590132
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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 |
Medical pharmacy
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| Research Institution | University of Shizuoka |
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Principal Investigator |
FUKUSHIMA Takeshi University of Shizuoka, School of Pharmarceuticall Sciences, Associate Professor (00272485)
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| Project Period (FY) |
2005 – 2007
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| Keywords | Schizophrenia / Kynurenic acid / Kvnurenine / Ketamine / N-acetylaspartic acid / Column-switching HPLC / Fluorescence detection / Microdialyysis |
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| Research Abstract |
In 2005 - 2007, we first developed highly sensitive determination methods for kynurenic acid, kynurenine, N-acetylaspartic acid, amino acids, serotonin, and catecholamines and their metabolites,so on. Using these originally developed methods, novel findings listed below were obtained in our laboratory.
1. Plasma kynurenic acid was significantly increased in the ketamine-treated rats.
2. Plasma glutamate was significantly increased, while cerebrospinal fluids glutamate was significantly decreased in the ketamine-treated rats.
3. Following an intraperitoneal administration of D, L-kynurenine, AUC value of plasma D-KYN was significantly lower than that of L-KYN.
4. Plasma glutamate was significantly increased in the male schizophrenic patients, while plasma proline was significantly increased in the female patients.
5. Plasma kynurenic acid was unequivocally increased following intraperitoneal D-kynurenine administration to male rats. It was suggested that D-Amino acid oxidase was responsible for the production of kynurenic acid from D-kynurenine.
6. During constant infusion of N-acetyl-L-aspartic acid to rat prefrontal cortex, an increase of kynurenic acid accompanied by decreases of glutamate and glycine in the microdialysis sample was observed.
These findings are expected to be useful information for the further research on the schizophrenia.
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