| Project/Area Number |
11670936
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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 |
Psychiatric science
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| Research Institution | TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY |
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Principal Investigator |
SUZUKI Michio Toyama Medical and Pharmaceutical University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (40236013)
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| Co-Investigator(Kenkyū-buntansha) |
KURACHI Masayoshi Toyama Medical and Pharmaceutical University, Faculty of Medicine, professor, 医学部, 教授 (80019603)
MURATA Masahiko Toyama Medical and Pharmaceutical University, Hospital, Assistant Professor, 附属病院, 助手 (20293318)
SUMIYOSHI Tomiki Toyama Medical and Pharmaceutical University, Hospital, Assistant Professor, 附属病院, 講師 (80286062)
黒川 賢造 富山医科薬科大学, 附属病院, 講師 (10283079)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | glutamate / N-acetylated alpha-linked acidic dipeptidase (NAALADase) / N-methyl-D-aspartate (NMDA) receptor / antisense oligodeoxynucleotide / dopamine D2 receptor / phencyclidine / social interaction / schizophrenia / 精神分裂病 / 分子遺伝学 / ノックダウン / in situ ハイブリダイゼーション |
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| Research Abstract |
Following studies were undertaken to investigate the pathophysiology underlying abnormalities of glutamatergic transmission in schizophrenia. First, a molecular genetic abnormality in gene encoding N-acetylated alpha-linked acidic dipeptidase (NAALADase) was investigated in patients with schizophrenia. Second, experimental studies were performed using several possible animal models of schizophrenia. Rats administered with antisense oligonucleotide complementary to mRNA of NAALADase into the bilateral entorhinal cortex did not show changes in spontaneous locomotor activity or metamphetamine-induced locomotor activity. Intracerebroventricular administration to rats with antisense oligonucleotide complementary to mRNA of N-methyl-D aspartate (NMDA) R1 subunit induced a significant reduction in dopamine D2 receptor density in the substantia nigra using in vitro [3H] YM-09151-2 autoradiography as well as a significant increase in dopamine D2 mRNA in the striatum using northern blot analysis. In rats treated chronically with non-competitive NMDA antagonist, phencyclidine or MK-801, behaviors related social interaction were significantly decreased.
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