Investigation of molecular mechanisms of LINE-1 regulation related to psychiatric disorders using animal models
| Project/Area Number |
18K15520
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 52030:Psychiatry-related
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| Research Institution | Kumamoto University |
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Principal Investigator |
Murata Yui 熊本大学, 大学院生命科学研究部(医), 特別研究員(SPD・PD・RPD) (10802077)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | LINE-1 / レトロトランスポゾン / 統合失調症 / poly(I:C) / 母体免疫活性 / 脳発達 / 胎生期 / エピゲノム / DNAメチル化 / 行動解析 / モデル動物 |
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| Outline of Final Research Achievements |
LINE-1 copy number was increased in the brain tissue of schizophrenic patients. However, the molecular mechanisms and the roles of LINE-1 retrotransposition in the brain are unknown. We used poly(I:C)-treated mouse, a commonly used animal model of psychiatric disorders, and confirmed that adult mice of this model showed behavioral abnormalities. We found that expression of of LINE mRNA was increased in prenatal brain. From RNA sequencing analysis of prenatal brain, expression of the genes related to RNA processing was increased. These data provided the possible regulatory mechanisms of brain LINE-1 overexpression in schizophrenia.
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| Academic Significance and Societal Importance of the Research Achievements |
精神疾患の発症メカニズムはいまだ不明点が多く、その分子機構を解明することは急務である。また、脳におけるLINE-1転写・転移活性メカニズムやその影響についても解明されていない。LINE-1新規転移がどのように生じ、脳機能の異常に関与するのかを検証することは、精神疾患の病態を解明する一助になると考えられる。胎生期の免疫活性ストレスによるLINE-1制御メカニズムが明らかになれば、精神神経疾患の予防・治療戦略に寄与できると期待される。
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Report
(3 results)
Research Products
(25 results)
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[Journal Article] Excess hydrogen sulfide and polysulfides production underlies a schizophrenia pathophysiology2019
Author(s)
Ide M, Ohnishi T, Toyoshima M, Itokawa M, Hirokawa N, Kunii Y, Kakita A, Yabe H, Iwamoto K, Meno K, Katagiri T, Dean B, Uchida K, Kimura H, Yoshikawa T.
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Journal Title
EMBO Mol Med
Volume: 11(12)
Issue: 12
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] DNA methylation analyses of the candidate genes identified by a methylome-wide association study revealed common epigenetic alterations in schizophrenia and bipolar disorder.2018
Author(s)
Sugawara H, Murata Y, Ikegame T, Sawamura R, Shimanaga S, Takeoka Y, Saito T, Ikeda M, Yoshikawa A, Nishimura F, Kawamura Y, Kakiuchi C, Sasaki T, Iwata N, Hashimoto M, Kasai K, Kato T, Bundo M, Iwamoto K.
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Journal Title
Psychiatry and Clinical Neurosciences
Volume: in press
Pages: 245-254
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] DNA methylation analyses of the candidate genes identified by a methylome-wide association study revealed common epigenetic alterations in schizophrenia and bipolar disorder2018
Author(s)
Sugawara H, Murata Y, Ikegame T, Sawamura R, Sasaki T, Iwata N, Hashimoto M, Kasai K, Kato T, Bundo M, Iwamoto K
Organizer
31st CINP World congress of neuropsychopharmacology
Related Report
Int'l Joint Research
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