Elucidation of the molecular basis of miRNAs related to neurodevelopmental disorders of schizophrenia

2017 Fiscal Year Final Research Report

• 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
• Keywords: 統合失調症 / miRNA / 神経発達

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.

Free Research Field

分子精神医学