| Project/Area Number |
15K09849
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Psychiatric science
|
|---|
| Research Institution | Institute of Physical and Chemical Research |
|---|
Principal Investigator |
toyoshima manabu 国立研究開発法人理化学研究所, 脳科学総合研究センター, 研究員 (90582750)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
吉川 武男 国立研究開発法人理化学研究所, その他, 研究員 (30249958)
|
|---|
| Project Period (FY) |
2015-04-01 – 2018-03-31
|
| Project Status |
Completed (Fiscal Year 2017)
|
| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
|---|
| Keywords | 統合失調症 / miRNA / 神経発達 / iPS細胞 / 神経分化 / 22q11.2欠失 / DGCR8 |
|---|
| Outline of Final Research Achievements |
We established hiPSCs from two schizophrenia patients with the 22q11.2 deletion, and examined the molecular pathology of microRNA (miRNA) related to abnormality of neuronal differentiation/development. Neurosphere size, neural differentiation efficiency, neurite outgrowth, cellular migration and the neurogenic-to-gliogenic competence ratio were significantly reduced in patient-derived cells. miRNA profiling detected reduced expression levels of miRNAs belonging to miR-17/92 cluster and miR-106a/b in the patient-derived neurospheres. Those miRNAs are reported to target p38, and conformingly the levels of p38 were up-regulated in the patient-derived cells. Furthermore, we confirmed an elevated expression of gliogenic (astrocyte) marker in postmortem brains from schizophrenia patients. These results suggest that a dysregulated balance of neurogenic and gliogenic competences may underlie schizophrenia.
|
