1993 Fiscal Year Final Research Report Summary
Study on pathoetilogy of schizophrenia and epilepsy fowsing on EAA newrons
| Project/Area Number |
03304036
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| Research Category |
Grant-in-Aid for Co-operative Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Psychiatric science
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| Research Institution | Tokyo Medical and Dental University, School of Medicine |
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Principal Investigator |
TORU Michio Tokyo Med.& Dent.Univ., Sch.of Med., Professor, 医学部, 教授 (20013972)
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| Co-Investigator(Kenkyū-buntansha) |
ALIYAMA Kazufumi Okayama Univ., Sch.of Med., Ass.prof., 医学部, 講師 (40150990)
YONEDA Yukio Setsunan Univ., Depart.of Pharm., Ass.Prof., 薬学部, 助教授 (50094454)
NISHIKAWA Toru Nat.Cent.of Neurl.& Psych., Section Chief, 神経センター,神経研究所, 室長 (00198441)
KAWAI Nobufumi Jichi Medical School Professor, 教授 (00073065)
KAYAMA Tsukasa Hokkaido Univ.Sch.of Med., Professor, 医学部, 教授 (10113557)
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| Project Period (FY) |
1991 – 1993
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| Keywords | Exatatory amino acid / schizophrenia / epilepsy / phencyclidine / NMDA receptor / dopamine / newrotoxin / brain |
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| Research Abstract |
1. Glycine binding sites associated with NMDA receptors were increased in the cerebral cortex of postmortem brain of chronic schizophrenics, supporting the glutamate hypothesis of schizophrenia.
2. NMDA receptors may give a tonic inhibition upon dopaminergic neurons through GABAergic interneurons in the rat medial frontal cortex.
3. Abnormal behavior produced by NMDA antagonists was inhibited by the compunds which stimulate NMDA receptor function. D-serine, an agonist of NMDA receptors, was found to localize in the rat and human brain.
4. A long-lasting increase in metabotropic receptor-coupled PI turnover was obserbed in the amygdala/piriform cortex of kindled rats, although no change in the contents of mRNA of metabotoropic receptors was found in the brain area. The long-lasting increase may play a role on the kindling mechanism.
Intraventricular administation of quinolinic acid induces seizure, stimulating NMDA receptors. In addition, low dose and large dose of quinolinate may activate NO system and two types (L and T) Ca^<2+> channel, respectively.
Increases in intracellular Ca^<2+> and glutamate-induced Ca^<2+> current through non-NMDA receptors, and abnormal PI turnover may be involved in the mechanism of delayd neuronal death.
7. Large doses of methamphetamine produced reductions in dopamine and dopamine metabolites in the rat brain, stimulating glutamate transmission through NMDA receptors.
There are heterogenous types of NMDA receptor complex in the rat brain, which were supported by the receptor binding experiements and by the measurements of DNA binding activities of transcription factors.
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