| Project/Area Number |
18390056
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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 |
General anatomy (including Histology/Embryology)
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| Research Institution | Tohoku University |
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Principal Investigator |
KONDO Hisatake Tohoku University, Tohoku University Graduate School of Medicine, Department of Cell Biology, Professor (20004723)
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| Co-Investigator(Kenkyū-buntansha) |
OWADA Yuji Yamaguchi University Graduate School of Medicine, Department of Human Morphology, Professor (20292211)
SAKAGAMI Hiroyuki Kitasato University, School of Medicine, Department of Anatomy, Professor (90261528)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥16,500,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥2,100,000)
Fiscal Year 2007: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Fiscal Year 2006: ¥7,400,000 (Direct Cost: ¥7,400,000)
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| Keywords | Brain-type FABP / Epidermal-type FABP / Fear and Anxiety, / Schizophrenia / Dendritic cells / IL-12, / 脂肪酸結合タンパク / 脾臓樹状細胞、 / 不安・恐怖記憶、 / 脳型(B-)、表皮型(E-) / 遺伝子欠損マウス、 / IL-12産生制御 / 脂肪酸 / マウス / 樹状細胞 / マクロファージ / PPAR |
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| Research Abstract |
Mutant mice for epidermal (E)-type and brain (B)-type fatty acid binding proteins (FABPs) were successfully generated as the first attempts in the world by us and they were fully analyzed throughout the project. The mutants for B-FABP exhibited enhanced anxiety and increased fear memory in the behavioral examination, while they decreased the content of docosahezaenoic acid (DHA) in the brain only at neonatal period without any histological changes in the brain at adult or neonate stages. The B-FABP mutants also showed decreased prepulse inhibition whose deficits are a biological marker for schizophrenia. All the data suggest a novel and crucial role of B-FABP in the pathology of schizophrenia. The mutants for E-FABP exhibited a lower mortality rate in the peritonitis by infection of Salmonella as compared with the wild counterpart. By in vitro analysis, dendritic cells isolated from the mutant spleen showed enhanced production of IL-12p70 in response to appropriate stimuli and higher levels of phosphorylated forms of p38 mitogen-activated protein kinase and IkBa after LPS stimulation as compared with the wild. These results suggest that the lower mortality rate in the peritonitis of the mutants was due to the possible role of E-FABP as a negative regulator of IL-12 production in the dendritic cells.
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