| Project/Area Number |
13470487
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Kanazawa University |
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Principal Investigator |
YONEDA Yukio Kanazawa University, Graduate School of Natural Science and Technology, Professor, 自然科学研究科, 教授 (50094454)
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| Co-Investigator(Kenkyū-buntansha) |
HINOI Eiichi Kanazawa University, Faculty of Pharmaceutical Sciences, Research Assistant, 薬学部, 助手 (70360865)
TANIURA Hideo Kanazawa University, Graduate School of Natural Science and Technology, Associate Professor, 自然科学研究科, 助教授 (80263325)
NAKAMURA Yoichi Osaka Prefecture University, Graduate School of Agriculture and Life Sciences, Professor, 大学院・農学生命科学研究科, 教授 (90180413)
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| Project Period (FY) |
2001 – 2003
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| Keywords | Stress / Activator protein-1 / cAMP response element binding protein / DNA binding / Transcription factors / BrdU incorporation / Dentate gyrus / Adult neurogenesis |
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| Research Abstract |
The present study deals with evaluation of molecular mechanisms associated with crisis of the posttraumatic disorder often seen with subjects in severe stressful situations. Patients would recall the stressful experience they had before months and years later. This could involve long-term consolidation of transient signals through modulation of de novo synthesis of particular target proteins at the level of gene transcription in the brain. Transcription factors are nuclear proteins with high affinity for a particular core nucleotide sequence to modulate the activity of RNA polymerase II that is responsible for the formation of mRNA from genomic DNA in the nucleus. Animals were subjected to cold and immobilization stress for different periods, followed by dissection of discrete central and peripheral structures and subsequent preparation of nuclear extracts for determination of DNA binding activity of different transcription factors. A marked increase was seen in DNA binding activities of activator protein-1(AP1) and cyclic AMP responsive element binding protein (CREB) in the rat hypothalamus, pituitary and adrenal glands, but not in the cerebral neocortex, hippocampus and striatum. By contrast, cold and immobilization stress induced a significant decrease in the number of clusters formed by cells immunoreactive to 5-bromo-deoxyuridine(BrdU) in the granular layer of the dentate gyrus in mouse hippocampus. These results suggest that severe stressful situation would lead to attenuation of adult neurogenesis through modulation of gene expression by transcription factors in the brain. Search for the target genes is undoubtedly of great importance for the therapy and treatment of posttraumatic disorder in human beings.
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