2013 Fiscal Year Final Research Report
Involvement of a co-factor of Notch signaling, Mastermind, into Schizophrenia
| Project/Area Number |
24659143
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Chiba University |
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Principal Investigator |
KITAGAWA Motoo 千葉大学, 医学(系)研究科(研究院), 准教授 (40262026)
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| Co-Investigator(Kenkyū-buntansha) |
TANIGAKI Kenji 滋賀県立成人病センター, 研究員 (70362473)
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| Co-Investigator(Renkei-kenkyūsha) |
HASHIMOTO Kenji 千葉大学, 社会精神保健教育研究センター, 教授 (10189483)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Keywords | Notchシグナル / 統合失調症 |
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| Research Abstract |
During Notch signaling, ligand stimulation induces generation of Notch intracellular domain, which is subsequently transported to the nuclei. With a DNA-binding protein RBP-J and a transcriptional co-activator Mastermind (Mam), the Notch intracellular domain forms a trimeric complex that activates transcription from the target promoters. We had found that heterozygous knockout mice of one of Mam genes, MamL1, exhibit increased sensitivity to dopamine, mimicking a part of symptoms of schizophrenia in humans. We have found heterozygous knockout mice of Rbp-j also exhibit very similar phenotype. Furthermore, by examining blood-derived genomic DNA from schizophrenic patients and healthy controls, we have found schizophrenia-specific missense polymorphisms in coding regions of both RBP-J and MAML1 genes. We are examining effects of these polymorphisms on the functions of these proteins.
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[Journal Article] A prospective comparative study of risperidone long-acting injectable for treatment-resistant schizophrenia with dopamine supersensitivity psychosis2014
Author(s)
Kimura H., Kanahara N., Komatsu N., Ishige M., Muneoka K., Yoshimura M., Yamanaka H., Suzuki T., Komatsu H., Sasaki T., Hashimoto T., Hasegawa T., Shiina A., Ishikawa M., Sekine Y., Shiraishi T., Watanabe H., Shimizu E., Hashimoto K., Iyo M
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Journal Title
Schizophrenia Res.
Volume: 155
Pages: 52-58
DOI
Peer Reviewed
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[Journal Article] Tipepidine in children with Attention-Deficit/Hyperactivity Disorder : A 4-week, open-label, preliminary study2014
Author(s)
Sasaki T., Hashimoto K., Tachibana M., Kurata T., Okawada K., Ishikawa M., Kimura H., Komatsu H., Ishikawa M., Hasegawa T., Shiina A., Hashimoto T., Kanahara N., Shiraishi T., Iyo M
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Journal Title
preliminary study. Neuropsychiatrc. Dis. Treatment
Volume: 10
Pages: 147-151
Peer Reviewed
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[Journal Article] MAML1 enhances the transcriptional activity of Runx2 and plays a role in bone development2013
Author(s)
Watanabe T., Oyama T., Asada M., Harada D., Ito Y., Inagawa M., Suzuki Y., Sugano S., Katsube K., Karsenty G., Komori T., Kitagawa M., Asahara H
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Journal Title
PLOS Genet.
Volume: 9
Pages: e1003132
DOI
Peer Reviewed
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[Journal Article] Deficits in microRNA-mediated Cxcr4/Cxcl12 signaling in neurodevelopmental deficits in a 22q11 deletion syndrome mouse model2013
Author(s)
Toritsuka M., Kimoto S., Muraki K., Landek-Salgado M.A., Yoshida A., Yamamoto N., Horiuchi Y., Hiyama H., Tajinda K., Keni N., Illingworth E., Iwamoto T., Kishimoto T., Sawa A., Tanigaki K
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Journal Title
Proc. Natl. Acad. Sci. USA.
Volume: 110
Pages: 17552-17557
DOI
Peer Reviewed
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[Journal Article] Decreased serum levels of mature brain-derived neurotrophic factor (BDNF), but not its precursor proBDNF, in patients with major depressive disorder2012
Author(s)
Yoshida T., Ishikawa M., Niitsu T., Nakazato M., Watanabe H., Shiraishi T., Shiina A., Hashimoto T., Kanahara N., Hasegawa T., Enohara M., Kimura H., Iyo M., Hashimoto K
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Journal Title
PLoS One
Volume: 7
Pages: e42676
DOI
Peer Reviewed
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[Journal Article] A randomized, double-blind, placebo-controlled trial of fluvoxamine in patients with schizophrenia : a preliminary study2012
Author(s)
Niitsu T., Fujisaki M., Shiina A., Yoshida T., Hasegawa T., Kanahara N., Hashimoto T., Shiraishi T., Fukami G., Nakazato M., Shirayama Y., Hashimoto K., Iyo M
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Journal Title
J. Clin. Psychopharmacol.
Volume: 32
Pages: 593-601
DOI
Peer Reviewed
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