2001 Fiscal Year Final Research Report Summary
The study for molecular mechanisms of antidepressant.
| Project/Area Number |
11670965
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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 | SHOWA UNIVERSITY |
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Principal Investigator |
KAMIJIMA Kunitoshi SHOWA UNIVERSITY, School of Medicine, Professor, 医学部, 教授 (80051613)
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| Co-Investigator(Kenkyū-buntansha) |
YAMADA Mitsuhiko Showa University, School of Medicine, Assistant Professor, 医学部, 講師 (60240040)
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| Project Period (FY) |
1999 – 2001
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| Keywords | antidepressant / depression / SSRI / RNA fingerprinting / Differential Display / gene / molecular biology |
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| Research Abstract |
We have identified 200 partial cDNA fragments (ADRG1 -200) as antidepressant related genes/expressed sequence tags (ESTs), with RNA fingerprinting (differential display) technique. In these ADRG genes
1. ADRG#27 was identified as a novel splice variant of 70 kDa heat shock cognate protein (HSC70), while screening differentially expressed molecules in rat brain after chronic antidepressant treatment. The expression of this clone, named HSC49, was increased after antidepressant treatment. On the other hand, these treatments had no effects on HSC70 expression.
2. The nucleotide sequence of the full length of ADRG#34 was determined. This cDNA encoded 685 amino acid residues yielding a mass of 79 kDa, containing a RING-H2 finger motif at the carboxy-terminus. RT-PCR Analysis demonstrated the induction of ADRG#34 at mRNA levels in rat hippocampus and the frontal cortex.
3. The homology analysis with the EMBL-Gene Bank database showed ADRG#55 matched perfectly with rat cysteine string protein (CSP). CSPs are unique cysteine-rich proteins which were originally identified as a family of nervous system specific antigens in Drosophila. RT-PCR and Western blot analysis confirmed the induction of CSP in rat frontal cortex after chronic treatment with two different classes of antidepressant, imipramine or sertraline. On the other hand, single administration of antidepressant was not increased CSP expression.
In conclusion, our results may contribute to a novel model for the therapeutic mechanism of depression and new molecular targets for the development of therapeutic agents.
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[Publications] Yamada, M., Yamada, M., Kiuchi, Y, Nara, K, Kanda, Y, Morinobu, S, Momose, K, Oguchi, K, Kamijima, K. Higuchi, T: "Identification of a novel splice variant of heat shock cognate protein 70 after chronic antidepressant treatment in rat frontal cortex."Biochem Biophys Res Commun. 261. 541-5 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Yamada, M., Yamada, M., Yamazaki, S., Takahashi, K., Nishioka, G., Kudo, K., Ozawa, H., Yamada, S., Kiuchi, Y., Kamijima, K., Higuchi, T. and Momose, K: "Identification ofanovel genewith RING-H2 finger motif induced after chronic antidepressant treatment in rat brain."Biochem Biophys Res Commu. 278. 50-157 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Yamada M, Yamada M, Yamazaki S, Takahashi K, Nara K, Osawa H, Yamada S, Kiuchi Y, Oguchi K, Kamijima K, Higuchi T, Momose K: "Induction of cysteine string protein after chronic antidepressant treatment inrat frontal cortex."Neurosci Lett. 301. 83-186 (2001)
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「研究成果報告書概要(欧文)」より
