2004 Fiscal Year Final Research Report Summary
A neurodevelopmental pharmacological approach to the molecular pathophysiology of schizophrenic symptoms
| Project/Area Number |
14207040
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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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 | Tokyo Medical and Dental University |
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Principal Investigator |
NISHIKAWA Toru Tokyo Medical and Dental University Graduate School, Section of Psychiatry and Behavioral Sciences, Professor, 大学院・医歯学総合研究科, 教授 (00198441)
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| Co-Investigator(Kenkyū-buntansha) |
KURUMAJI Akeo Tokyo Medical and Dental University School of Medicine, Section of Psychiatry and Behavioral Sciences, Lecturer, 医学部附属病院, 講師 (00251504)
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| Project Period (FY) |
2002 – 2004
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| Keywords | Schizophrenia / Methamphetamine / Phencyclidine / Neocortex / Positive symptoms / Negative symptoms / Gene expression / Postnatal development |
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| Research Abstract |
Schizophrenic symptoms typically occur after the adolescence and the ability of psychotogenic drugs to induce schizophrenia-like psychosis is also age-dependent. Moreover, the behavioral responses to schizophrenomimetic drugs in experimental animals as pharmacological models of schizophrenia apparently depend upon postnatal development. The late developing manifestation of schizophrenia and its models suggest that the molecular cascades impaired in schizophrenia could be affected by or responsive to schizophrenomimetics only after the adolescence in humans or the critical period in experimental animals when the specific cascades might maturate. To obtain insight into the molecules that are specifically related to schizophrenia based upon the developmental features, we investigated in the developing rats the effects of schizophrenomimetic drugs, methamphetamine (MAP : a DA agonist which causes the schizophrenia-like positive symptoms) and phencyclidine (PCP : a NMDA antagonist causing schizophrenia-like positive and negative symptoms), on gene expression in the brain using a differential cloning technique and RT-PCR. We further studied the pharmacological profiles and the human homologues of previously identified a developmentally-regulated and MAP-responsive (mrt1) or PCP-responsive (prt1) gene in the neocortex In addition, we isolated the novel candidates for schizophrenia-related genes, mrt3 and prt4 from the neocrtex.
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Research Products
(72 results)
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[Journal Article] Effects of Endogenous Agonists, Glycine and D-Serine, on In Vivo Specific Binding of [11C]L-703,717, a PET Radioligand for the Glycine-Binding Site of NMDA Receptors.2003
Author(s)
Haradahira T, Okauchi T, Maeda J, Zhang M-R, Nishikawa T, Konno R, Suzuki K, Suhara T.
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Journal Title
Synapse 50
Pages: 130-136
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Mammalian septins nomenclature.2002
Author(s)
Macara IG, Baldarelli R, Field CM, Glotzer M, Hayashi Y, Hsu S-H, Kennedy MB, Kinoshita M, Longtine M, Low C, Maltais LJ, McKenzie L, Mitchison T, Nishikawa T, Noda M, Petty EM, Peifer M, Pringle JR, Robinson PJ, Roth D, Russell SEH, Stuhlmann H, Tanaka M, Tanaka T, Trimble WS, Ware J, Zeleznik-Le NJ, Zieger B.
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Journal Title
Mol Biol Cell 13
Pages: 4111-4113
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A Family-based Association Study and Gene Expression Analyses of Netrin-G1 and -G2 Genes in Schizophrenia.
Author(s)
Aoki-Suzuki M, Yamada K, Meerabux J, Iwayama-Shigeno Y, Ohba H, Iwamoto K, Takao H, Toyota T, Suto Y, Nakatani N, Dean B, Nishimura S, Seki K, Kato T, Itohara S, Nishikawa T, Yoshikawa T.
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Journal Title
Biol Psychiatry (in press)
Description
「研究成果報告書概要(欧文)」より
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