| Project/Area Number |
16592047
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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 |
Orthodontic/Pediatric dentistry
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| Research Institution | OKAYAMA UNIVERSITY |
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Principal Investigator |
KITAYAMA Shigeo Okayama University, Graduate School of Medicine, Dentistry and Phaemaceutical Sciences, Professor, 大学院医歯薬学総合研究科, 教授 (80177873)
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| Co-Investigator(Kenkyū-buntansha) |
DOHI Toshihiro Hiroshima University, Graduate School of Biomedical Sciences, Professor, 大学院医歯薬学総合研究科, 教授 (00034182)
KOZAI Katsuyuki Hiroshima University, Graduate School of Biomedical Sciences, Professor, 大学院医歯薬学総合研究科, 教授 (10178212)
SOGAWA Chiharu Okayama University, Graduate School of Medicine, Dentistry and Phaemaceutical Sciences, Research Associate, 大学院医歯薬学総合研究科, 助手 (10253022)
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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: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Gene / Environment / Dentistry / Brain / Neuron / Pharmacology / Neurotransmitter / Dopamine / Transporter / 注意欠陥多動性障害(ADHD) / 内分泌攪乱物質 / 環境ホルモン / 転写 / プロモーター |
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| Research Abstract |
Attention-deficit hyperactivity disorder (ADHD) is a mental illness occurred in childhood, and thought to be related to the changes in dopaminergic neural activity, especially in dopamine transporter (DAT), which is known to regulate synaptic dopamine (DA) concentration by reuptake of released DA. To explore the possible relationship between regulated expression of DAT and ADHD, we focused on the transcriptional regulation of DAT gene expression by environmental factors as stressor.
We examined the influence of estrogen and estrogen-like environmental substance such as bisphenol-A (BPA) on the expression of DAT gene by assessment of DAT mRNA and protein levels in the mouse brain and culture cells, and of the promorter activity of DAT gene by transfection assay using luciferase importer gene in various cell lines.
Analyses of database indicate the possible estrogen-responsible elements (ERE) in the 5'-flanking region (〜10kb) upstream of the transcription start site of human DAT gene. Treatment with 17β-estradiol (20 nM) for 24 h inhibited the transcriptional activity of hDAT gene construct pD10.1which includes multiple ERE, whereas it enhanced the activity of hDAT construct pD2.4 which is without ERE. BPA at same concentration revealed enhancement of the promotor activity of pD2.4 without affecting that of pD10.1.
These results demonstrated that estrogen and estrogen-like environmental substances influence the DAT gene expression at transcriptional regulation, and suggested that they reveal the inhibitory mechanism through ERE and facilitatory mechanism through that other than ERE..
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