Study for the molecular basis of affective disorders caused by the dysregulated homeostasis of endocrine system
| Project/Area Number |
20240038
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Osaka University |
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Principal Investigator |
SOBUE Kenji Osaka University, 医学系研究科, 教授 (20112047)
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| Co-Investigator(Kenkyū-buntansha) |
HAYASHI Ken'ichiro 大阪大学, 医学系研究科, 准教授 (90238105)
MORITA Tsuyoshi 大阪大学, 医学系研究科, 助教 (80403195)
MAYANAGI Taira 大阪大学, 連合小児発達学研究科, 特任助教(常勤) (20432544)
FUKUMOTO Kentar 大阪大学, 医学系研究科, 助教 (00514407)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥51,610,000 (Direct Cost: ¥39,700,000、Indirect Cost: ¥11,910,000)
Fiscal Year 2010: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
Fiscal Year 2009: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
Fiscal Year 2008: ¥32,110,000 (Direct Cost: ¥24,700,000、Indirect Cost: ¥7,410,000)
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| Keywords | 感情障害 / グルココルチコイド / ストレス / 大脳形成障害 / シナプス形成障害 / 内分泌 / 甲状腺ホルモン / 内分泌恒常性 / 大脳皮質形成 / カルデスモン / シナプス / 神経回路網 |
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| Research Abstract |
We found that glucocorticoid(GC)-dependent transient retardation during cerebral development was caused by the disturbance of neuronal migration via the GC receptor (GR)-dependent upregulation of caldesmon expression. After this transient retardation, insufficient neuronal network formation was found in the adolescent brain as revealed by MRI. These findings provide a novel insight regarding behavioral abnormalities and increased risks of affective disorders. We further established a GC-deficit neuronal cell culture system in which neurons can form synapses. Using this culture system, GCs were demonstrated to be detrimental for synaptic formation via the destabilization of actin filaments mediated by the downregulation of caldesmon expression. We also showed that the expression of caldesmon was downregulated by suppression of SRF co-regulator MRTF-B. Thus this study presents the molecular basis for understanding the onset of affective disorders caused by the dysregulation of GC-linked endocrine system.
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Report
(4 results)
Research Products
(40 results)
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[Book] 生物学辞典2010
Author(s)
石川統, 黒岩常祥, 塩見正衞, 松本忠夫, 守隆夫, 八杉貞雄, 山本正幸
Publisher
東京化学同人
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