| Project/Area Number |
17K16386
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Psychiatric science
|
|---|
| Research Institution | Kyushu University |
|---|
Principal Investigator |
Sagata Noriaki 九州大学, 医学研究院, 学術研究員 (00632308)
|
|---|
| Project Period (FY) |
2017-04-01 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
|
|---|
| Keywords | トランスレーショナル研究 / 自閉症スペクトラム障害 / ASD / 神経線維腫症1型 / NF1 / 直接誘導神経細胞 / iN細胞 / 分子精神医学 |
|---|
| Outline of Final Research Achievements |
Neurofibromatosis type 1 (NF1) is a multifaceted disease, and frequently comorbid with neurodevelopmental disorders such as autism spectrum disorder (ASD). Dysfunction of adenylyl cyclase (AC) is one of the candidate pathways in abnormal development of neuronal cells in the brain of NF1 patients, while its detailed abnormalities have not been revealed. Direct conversion technology can generate induced-neuronal (iN) cells directly from human fibroblasts. I have revealed that forskolin, an AC activator, rescues the gene expression pattern of iN cells derived from NF1 patients (NF1-iN cells) (Sagata et al., 2017).
Only 20 minutes after forskolin treatment, the morphology of the NF1-iN cells were dramatically changed from flat-form to spherical-form. Forskolin also enhanced neurite outgrowth of NF1-iN cells. Forskolin or AC activators may have therapeutic effects on the growth of neuronal cells in NF1 patients (Sagata et al., 2020 (in Press)).
|
| Academic Significance and Societal Importance of the Research Achievements |
自閉症スペクトラム障害（ASD）や学習障害などの神経発達障害と併存することがよくある神経線維腫症1型（NF1）に着目し、NF1患者由来の直接誘導神経（NF1-iN）細胞にみられた遺伝子発現異常および細胞の形態異常がフォルスコリンによって明らかな改善を示すことを明らかにした。
生検等では得られないヒトの神経細胞を線維芽細胞から誘導したiN細胞を利用し、細胞レベルでの解析を行うことによって薬剤の効果を比較的容易に評価する一つの手法を提示しつつ、フォルスコリンなどのアデニルシクラーゼ活性化剤のNF1ひいてはASDを含む神経発達障害の治療薬・予防薬としての可能性を示した。
|
