Functional analysis of Ccr3 associated with narcolepsy
| Project/Area Number |
26870117
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Environmental physiology(including physical medicine and nutritional physiology)
Psychiatric science
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
Toyoda Hiromi 東京大学, 大学院医学系研究科(医学部), 客員研究員 (90637448)
|
|---|
| Research Collaborator |
HONDA Yoshiko
KODAMA Tohru
TANAKA Susumu
MIYAGAWA Taku
|
|---|
| Project Period (FY) |
2014-04-01 – 2018-03-31
|
| Project Status |
Completed (Fiscal Year 2017)
|
| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
|
|---|
| Keywords | ナルコレプシー / 睡眠 / Ccr3 / ケモカイン受容体 / オレキシン細胞 / 睡眠障害 / CCR3 / ケモカインレセプター / ケモカイン / 神経免疫 |
|---|
| Outline of Final Research Achievements |
Narcolepsy is caused by the loss of hypocretin (Hcrt) neurons. Although abnormalities in immunity are suggested to be involved in the etiology of narcolepsy, no decisive mechanism has been established. I previously reported CCR3 as a novel susceptibility gene for narcolepsy. This study investigated sleep-wake patterns of Ccr3 KO mice to understand the role of CCR3 in the development of narcolepsy.
Ccr3 KO mice exhibited fragmented sleep patterns in the resting phase. Intraperitoneal injection of LPS promoted wakefulness and suppressed both REM and NREM sleep in the resting phase in both Ccr3 KO and WT mice. These LPS-induced changes in sleep patterns were larger in Ccr3 KO compared to WT mice. Furthermore, Ccr3 KO mice had fewer Hcrt neurons in the lateral hypothalamus compared to WT mice.
We propose that impaired function of Ccr3 causes fragmented sleep that can contribute to vulnerability to developing narcolepsy in an inflammatory context induced by environmental triggers.
|
Report
(5 results)
Research Products
(14 results)
-
-
-
[Journal Article] Evaluation of polygenic risks for narcolepsy and essential hypersomnia2016
Author(s)
Yamasaki M, Miyagawa T, Toyoda H, Khor SS, Liu X, Kuwabara H, Kano Y, Shimada T, Sugiyama T, Nishida H, Sugaya N, Tochigi M, Otowa T, Okazaki Y, Kaiya H, Kawamura Y, Miyashita A, Kuwano R, Kasai K, Tanii H, Sasaki T, Honda Y, Honda M, Tokunaga K
-
Journal Title
Journal of Human Genetics
Volume: 61(10)
Issue: 10
Pages: 873-878
DOI
NAID
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
-
-
[Journal Article] A polymorphism in CCR1/CCR3 is associated with narcolepsy.2015
Author(s)
Toyoda H, Miyagawa T, Koike A, Kanbayashi T, Imanishi A, Sagawa Y, Kotorii N, Kotorii T, Hashizume Y, Ogi K, Hiejima H, Kamei Y, Hida A, Miyamoto M, Imai M, Fujimura Y, Tamura Y, Ikegami A, Wada Y, Moriya S, Furuya H, Takeuchi M, Kirino Y, Meguro A, Remmers EF, Kawamura Y, Otowa T, Miyashita A, et al.
-
Journal Title
Brain Behav Immun.
Volume: 印刷中
Pages: 148-155
DOI
Related Report
Peer Reviewed
-
-
-
[Journal Article] High-accuracy imputation for HLA class I and II genes based on high-resolution SNP data of population-specific references.2015
Author(s)
Khor SS, Yang W, Kawashima M, Kamitsuji S, Zheng X, Nishida N, Sawai H, Toyoda H, Miyagawa T, Honda M, Kamatani N, Tokunaga K.
-
Journal Title
Pharmacogenomics J.
Volume: 未定
Issue: 6
Pages: 1-8
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
-
-
-
-
-
-
