Study on the regulatory roles of primary cilia relating to feeding and mood control
| Project/Area Number |
19K06739
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 44040:Morphology and anatomical structure-related
|
|---|
| Research Institution | Hiroshima University |
|---|
Principal Investigator |
Saito Yumiko 広島大学, 統合生命科学研究科(総), 教授 (00215568)
|
|---|
| Project Period (FY) |
2019-04-01 – 2022-03-31
|
| Project Status |
Completed (Fiscal Year 2021)
|
| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
|---|
| Keywords | Gタンパク質共役型受容体 / 一次繊毛 / 摂食 / 海馬 / RNAseq / アクチン結合タンパク質 / ベータアミロイド / 情動 / シグナル解析 / ヒトiPS / GPCR / うつ不安 / シナプス |
|---|
| Outline of Research at the Start |
メラニン凝集ホルモンMCHは摂食・情動を調節する神経ペプチドである。その受容体MCHR1は神経細胞一次繊毛に集積する。申請者は、MCHR1活性化は繊毛長短縮を起こすという特異な現象を見出した。本研究では、神経細胞一次繊毛のMCHR1活性化や短縮は神経細胞の機能に関わる各構造にどのような影響を与えるか、更に、一次繊毛を起点とした神経伝達が摂食・急性ストレスによりどのような影響を受けるか、個体レベルで検討する。これらの知見は、正常なシナプス伝達に干渉しない、一次繊毛を介した摂食や情動障害の新たな治療戦略となることが期待できる。
|
| Outline of Final Research Achievements |
The primary cilium is a plasma membrane-protruding sensory organelle that efficiently conveys signaling cascades in a highly ordered microenvironment. Its signaling is mediated, in part, by a limited set of GPCRs preferentially enriched in the cilium membrane. This includes melanin-concentrating hormone (MCH) receptor 1 (MCHR1), which plays a role in feeding and mood. By extensive biological and pharmacological studies of ciliary MCHR1, I have accomplished that (1) Discovery of the biological phenomenon “cilia length shortening via ciliary MCHR1” in MCHR1-expresing RPE1 cell and CA1 hippocampal neurons in vitro and in vivo (the starved state mice), (2) Identification of novel and important regulatory step underlying cilia length control via ciliary MCHR1, (3) Finding of impairment of ciliary dynamics in an APP knock-in mouse model of Alzheimer’s disease. Further, Aβ is found to reduce cilia length in cultured hippocampal neuron.
|
| Academic Significance and Societal Importance of the Research Achievements |
本研究により、肥満動物の繊毛縮退に繋がる可能性を持つ「繊毛縮退モデル系群（ヒトiPSを含む）」に加え、鋭敏なvivo検出系も完成することができた。さらに、繊毛発のMCHR1シグナリングリレー経路の存在も明らかにした。これらの結果は、これまでの細胞膜発現系を用いたGPCR研究では得られなかったものである。従って、神経突起やシナプスが主眼ではなく、非シナプス性小器官である1次繊毛からアプローチを行うことで、摂食情動に対する新たな治療薬の開発につながる可能性がある。
|
Report
(4 results)
Research Products
(46 results)
-
-
-
-
[Journal Article] Regulation of brain primary cilia length by MCH signaling: Evidence from pharmacological, genetic, optogenetic and chemogenic manipulations2022
Author(s)
Alhassen W, Kobayashi Y, Su J, Robbins B, Ngyuen H, Myint T, Yu M, Nauli S, Saito Y, Alachkar A.
-
Journal Title
Molecular Neurobiology
Volume: 59
Issue: 1
Pages: 245-265
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
[Journal Article] Patterns of cilia gene dysregulations in major psychiatric disorders.2021
Author(s)
Alhassen W, Siwei Chen S, Vawter M, Kay Robbins B, Nguyen H, Nyi Myint NT, Saito Y, Schulmann A, Nauli SM, Civelli O, Baldi P, Alachkar A
-
Journal Title
Progress in Neuropsychopharmacology & Biological Psychiatry.
Volume: 109
Pages: 110255-110255
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] Required research activities to overcome addiction problems in Japan.2021
Author(s)
Ikeda K, Ide S, Omoe H, Minami M, Miyata H, Kawato M, Okamoto H, Kikuchi T, Saito Y, Shirao T, Sekino Y, Murai T, Matsumoto T, Iseki M, Nishitani Y, Sumitani M, Takahashi H, Yamawaki S, Isa T, Kamio Y
-
Journal Title
Taiwanese J Psychiat
Volume: 35
Pages: 6-11
Related Report
Peer Reviewed
-
-
[Journal Article] Postsynaptic structure formation of human iPS cell-derived neurons takes longer than presynaptic formation during neural differentiation in vitro.2021
Author(s)
Togo K, , Fukusumi H, Shofuda T, Ohnishi H, Yamazaki H, Hayashi M, Kawasaki N, Takei N, Nakazawa T, Saito Y, Baba K, Hashimoto H, Sekino Y, Shirao T, Mochizuki H, Yanemura H
-
Journal Title
Mol Brain
Volume: 14
Issue: 1
Pages: 149-149
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
