| Project/Area Number |
18K06502
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 46020:Anatomy and histopathology of nervous system-related
|
|---|
| Research Institution | Shiga University of Medical Science |
|---|
Principal Investigator |
Katsuyama Yu 滋賀医科大学, 医学部, 教授 (10359862)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
金田 勇人 滋賀医科大学, 医学部, 准教授 (40528212)
椎野 顯彦 滋賀医科大学, 神経難病研究センター, 准教授 (50215935)
平賀 真理子 大阪大学, 歯学研究科, 講師 (50638757)
|
|---|
| Project Period (FY) |
2018-04-01 – 2021-03-31
|
| Project Status |
Completed (Fiscal Year 2020)
|
| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
|---|
| Keywords | 神経線維成長制御機構 / 皮質ニューロン分化 / 神経線維発達 / 大脳皮質 / 軸索伸長 / 大脳皮質発生 / ニューロン形態形成 / 樹状突起形成 / 神経発生 |
|---|
| Outline of Final Research Achievements |
Although involvement of Sbno1 in psychiatric diseases and brain development was suggested from human genome analyses, experimental study of Sbno1 to examine its function in brain had not been reported. We constructed Sbno1 deficient mouse strain, in which Sbno1 is specifically knocked out in the differentiating cortical neurons. In this mutant, atrophy in the corpus callosum and pyramidal tract was observed. We examine function of cortical motor neurons utilizing intracortical electric stimulation and found that Sbno1 knockout conical neurons require higher amplitude of electric current compared to control brain to induce movements of limbs. We also examined morphology of each single cortical neuron and found neurites were shorter in the knockout neurons compared to normal neurons.
Sbno1 binding candidates that we isolated by proteomics analysis included many transcription factors were, suggesting that Sbno1 involved in neuritis growth by regulating genes expression.
|
| Academic Significance and Societal Importance of the Research Achievements |
ヒトゲノム解析からSbno1は精神疾患や正常な脳の発達に関与していることが示唆されていた。本研究はSbno1は軸索や樹状突起の正常な発達に必要であることを示した。Sbno1は転写因子に結合する可能性が高いことからSbno1は遺伝子発現制御に関わることで神経ネットワークの正常な発達に必要な遺伝子である可能性が高い。Sbno1による遺伝子発現制御は新しい分子機構であり、脳の正常な発生について重要な知見を与える。本研究は将来的に精神疾患の新規診断方法や治療法の開発に貢献できることが期待される。
|
