Analysis of novel transcription factors for hypocretin and involvement of narcolepsy
| Project/Area Number |
16K08533
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Environmental physiology(including physical medicine and nutritional physiology)
|
|---|
| Research Institution | Kansai Medical University |
|---|
Principal Investigator |
TANAKA Susumu 関西医科大学, 医学部, 准教授 (30399472)
|
|---|
| Research Collaborator |
KODAMA Tohru
|
|---|
| Project Period (FY) |
2016-04-01 – 2019-03-31
|
| Project Status |
Completed (Fiscal Year 2018)
|
| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
|---|
| Keywords | オレキシン / 睡眠 / 覚醒 / PLAGL1 / 転写制御 / ナルコレプシー |
|---|
| Outline of Final Research Achievements |
The hypocretin/orexin neuropeptide coordinates the regulation of various physiological processes. Our previous study suggested that PLAGL1 is coexpressed in hypocretin neurons and regulates hypocretin transcription. The present study examined whether canonical prepro-hypocretin transcription is functionally modulated by PLAGL1.
The majority of hypocretin neurons were positive for PLAGL1 in the nucleus. Notably, PLAGL1 in hypocretin neurons was altered in response to several conditions affecting hypocretin function. An uneven localization of PLAGL1 was detectedfollowing sleep deprivation. ChiP-PCR revealed that endogenous PLAGL1 may bind to a putative PLAGL1 binding site in the proximal region of the hypocretin gene, in the murine hypothalamus. In addition, electroporation of the PLAGL1 expression vector into the fetal hypothalamus promoted hypothalamic hypocretin transcription.
These results suggested that PLAGL1 may regulate hypothalamic hypocretin transcription.
|
| Academic Significance and Societal Importance of the Research Achievements |
本研究により見いだされたオレキシン転写制御因子を用いることにより、ある程度オレキシンニューロンへの分化が決定した幹細胞のオレキシン発現を安定させられると考えられる。それはナルコレプシーの根本治療へとつながっていく。さらにオレキシンニューロン数を安定させることにより、ナルコレプシー患者血清ならびに脳脊髄液中に存在すると考えられているオレキシンニューロン脱落因子の探索を可能とし、ひいてはナルコレプシーの病態解明につながっていく。
|
Report
(4 results)
Research Products
(21 results)
-
[Journal Article] Involvement of PLAGL1/ZAC1 in hypocretin/orexin transcription.2019
Author(s)
Tanaka S, Honda Y, Takaku S, Koike T, Oe S, Hirahara Y, Yoshida T, Takizawa N, Takamori Y, Kurokawa K, Kodama T, Yamada H
-
Journal Title
Int J Mol Med.
Volume: 43(5)
Pages: 2164-2176
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Presentation] PLAGL1/ZAC1によるオレキシン転写制御2017
Author(s)
田中進, 本多芳子, 高久静香, 小池太郎, 大江総一, 平原幸恵, 滝澤奈恵, 高森康晴, 黒川清, 児玉亨, 山田久夫
Organizer
第123回日本解剖学会総会・全国学術集会
Related Report
-
