| Project/Area Number |
16591169
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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 | St.Marianna University School of Medicine |
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Principal Investigator |
OSADA Kenichi St.Marianna University School of Medicine, Department of Neuropsychiatry, Lecture, 医学部, 講師 (20233504)
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| Co-Investigator(Kenkyū-buntansha) |
ASAKURA Mikio St.Marianna University School of Medicine, Department of Neuropsychiatry, Assistant Professor, 医学部, 助教授 (70103504)
MATUI Hiroaki St.Marianna University School of Medicine, Radioisotope Research Institute, Professor, 医学部, 教授 (90181685)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2004: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | bHLH / Transcription Factor / Mood stabilizer / Proteomics / Lithium / Phosphorylation / GAP-43 / MATH / Math / eEF2 / 転写因 / E-box |
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| Research Abstract |
Lithium is a mood stabilizer used in treatment of bipolar disorders. We reported that the GAP-43 RNA expression and GAP-43 protein levels 1.5 times increased after 4-5 weeks lithium treatment in the rat brain. GAP-43 is known to play an important role in the releasing process for several neurotransmitters (Ach, 5-HT and DA). We also reported that MATH-2 transcription factor bind the GAP-43 promoter and increased in the expression for GAP-43.
MATH-2 increased the activity about 2.5 times compared with control in luciferase assay, and MATH-2 regulated GAP-43 gene expression than the other transcription factors. 5 weeks lithium treatment increased in the MATH-2 protein level about 4 times by immunoblot. Long-term lithium treatment translocated MATH-2 to nucleolus and nuclear membrane by immunohistochemistry.
We considered that MATH-2 induced increase of GAP-43 RNA and GAP-43 protein level and the long-term lithium treatment regulated GAP-43 by MATH-2.
We made MATH-2 overexpressed transgenic mice used □CaM Kinase II promoter. MATH-2 overexpressed transgenic mice activated movement in open field test, and located for long time in open arm, the other shorted time in closed arm for zero-mazed test. This indicated that MATH-2 overexpressed transgenic mice actived locomotion for anxiety and fear. The MATH-2 overexpressed transgenic mice have possibility for mood disorders model mice.
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