Development of therapeutic strategy for neurodevelopmental disorders based on site-specific microglial and microRNA functions
| Project/Area Number |
25460345
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
General pharmacology
|
|---|
| Research Institution | Nippon Medical School |
|---|
Principal Investigator |
Suzuki Hidenori 日本医科大学, 医学(系)研究科(研究院), 教授 (30221328)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SAITOW FUMIHITO 日本医科大学, 医学部, 准教授 (20360175)
SAKAI ATSUSHI 日本医科大学, 医学部, 講師 (30386156)
NAGANO MASATOSHI 日本医科大学, 医学部, 講師 (60271350)
|
|---|
| Project Period (FY) |
2013-04-01 – 2016-03-31
|
| Project Status |
Completed (Fiscal Year 2015)
|
| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
|---|
| Keywords | 自閉症動物モデル / 社会的行動 / 背側縫線核 / 発達障害 / 不安様行動 / 扁桃体 / microRNA / ミクログリア / セロトニン神経系 / 自閉症 / 発達障害モデル動物 / miRNA / オープンフィールド試験 / 中脳背側縫線核 |
|---|
| Outline of Final Research Achievements |
The underlying neural mechanisms of neurodevelopmental disorders including autism spectrum disorder (ASD) are poorly understood. We examined an involvement of microglia in ASD using mice with paternal duplication (patDp/+) corresponding to human chromosome 15q11-q13. Iba1, a microglial activation marker, was decreased in the basolateral amygdala in patDp/+ mice at postnatal day 7. Perinatal treatment with minocycline, a microglial modulator, restored the Iba1 expression in the basolateral amygdala and reduced anxiety-related behaviors in adolescence. Further, early postnatal treatment with a selective serotonin reuptake inhibitor, which has been reported to directly affect microglial functions, ameliorated a deficit in social interaction behavior in adolescence.
The results of the present study suggest important roles of microglia in pathophysiology of neurodevelopmental disorders and provide a key piece of information to develop novel microglia-related drugs for these disorders.
|
Report
(4 results)
Research Products
(25 results)
-
-
-
-
-
[Journal Article] Targeted deletion of the C-terminus of the mouse adenomatous polyposis coli tumor suppressor results in neurologic phenotypes related to schizophrenia2014
Author(s)
Takanori Onouchi, Katsunori Kobayashi, Kazuyoshi Sakai, Atsushi Shimomura, Ron Smits, Chiho Sumi-Ichinose, Masafumi Kurosumi Keizo Takao, Ryuji Nomura, Akiko Iizuka-Kogo, Hidenori Suzuki,Kazunao Kondo, Tetsu Akiyama Tsuyoshi Miyakawa Riccardo Fodde and Takao Senda, Riccardo Fodde, Takao
-
Journal Title
Molecular Brain
Volume: 7
Issue: 1
Pages: 21-21
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] Enhanced stability of hippocampal place representation caused by reduced magnesium block of NMDA receptors in the dentate gyrus2014
Author(s)
Yuichiro Hayashi, Yoko Nabeshima, Katsunori Kobayashi, Tsuyoshi Miyakawa, Koichi Tanda, Keizo Takao, Hidenori Suzuki, Eisaku Esumi, Shigeru Noguchi, Yukiko Matsuda, Toshikuni Sasaoka, Tesuo Noda, Jun-ichi Miyazaki, Masayoshi Mishina, Kazuo Funabiki and Yo-ichi Nabeshima
-
Journal Title
Molecular Brain
Volume: 7
Issue: 1
Pages: 44-44
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] Modafinil augments brain activation associated with reward anticipation in the nucleus accumbens.2014
Author(s)
Funayama, T., Ikeda, Y., Tateno, A., Takahashi, H., Okubo, Y., Fukuyama, H., & Suzuki, H.
-
Journal Title
Psychopharmacology
Volume: 231
Issue: 16
Pages: 3217-3228
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
