Analysis of new pathological phenomena in adult onset temporal lobe epilepsy and the potential therapeutic effect of glycated protein expression control
| Project/Area Number |
17K10908
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neurosurgery
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| Research Institution | Juntendo University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
宮嶋 雅一 順天堂大学, 医学部, 教授 (60200177)
新井 一 順天堂大学, 医学部, 教授 (70167229)
西村 欣也 順天堂大学, 医学部, 教授 (80164581)
菅野 秀宣 順天堂大学, 医学部, 先任准教授 (90265992)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 脳内環境 / 認知機能 / 側頭葉てんかん / ロイシンリッチα2グリコプロテイン / ピロカルピン酸 / パッチクランプ / 長期増強 / 予防医学 / 扁桃体腫大 / 炎症メディエーター / 糖化蛋白 / てんかん原性 / 扁桃体 / 海馬 / てんかん原生 / 脳波 / 神経科学 / トランスレーショナルリサーチ / 病理学 |
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| Outline of Final Research Achievements |
We verified the preventative effects of increasing the expression of leucine-rich alpha2 glycoprotein (LRG1) in the brain regarding the decline of cognitive function caused by epileptic seizures using an animal model of secondary temporal lobe epilepsy (TLE). Electrophysiological and molecular biological analyses were performed on adult secondary epileptogenic formation using an animal model of TLE induced with pilocarpine utilizing CAG-loxP-GFP-loxP-LRG1 transgenic mice (LRG-Tg). The cognitive behavioral experiments indicated a significant decline in cognitive function and significant reduction in LTP was confirmed in the control mouse after status epilepticus (SE). Neural dropout in the CA1 region of the hippocampus was particularly marked. However, LTP reduction was not observed in the LRG-Tg mice after SE. LRG1 expression in the hippocampus was confirmed to suppress nerve cell firing and prevent cognitive function decline after SE.
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| Academic Significance and Societal Importance of the Research Achievements |
疾患耐性に対する脳内環境に関する研究は，後天的に発症する神経疾患に対する予防的対策となる。後天性疾患である側頭葉てんかんに対して，発症を予防し，かつ認知機能を維持する脳内環境を考察した学術的意義の高い研究である。本研究は，糖化蛋白であるロイシンリッチα2グリコプロテインが増加した脳内環境下では，けいれん重積からてんかん原性が形成されることを予防し，認知機能を保つことを証明した。側頭葉てんかんの発症を抑止する脳保護作用をもつ脳内環境を安全に提供することができれば，創薬へ発展する可能性がある。
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Report
(5 results)
Research Products
(35 results)
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[Journal Article] Preoperative phosphorylated tau measurement of cerebrospinal fluid can predict cognitive function 3 years after shunt surgery in patients with idiopathic normal pressure hydrocephalus.2018
Author(s)
Madoka Nakajima, Masakazu Miyajima, Ikuko Ogino, Chihiro Akiba, Kaito Kawamura, Yoshinao Harada, Takeshi Hara, Hidenori Sugano, Kostadin Karagiozov, Takeshi Ikeuchi, Takahiko Tokuda, Hajime Arai
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Journal Title
J Alzheimers Dis.
Volume: 66
Issue: 1
Pages: 319-331
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Change of Amyloid-β 1-42 Toxic Conformer Ratio After Cerebrospinal Fluid Diversion Predicts Long-Term Cognitive Outcome in Patients with Idiopathic Normal Pressure Hydrocephalus2018
Author(s)
Akiba C, Nakajima M, Miyajima M, Ogino I, Motoi Y, Kawamura K, Adachi S, Kondo A, Sugano H, Tokuda T, Irie K, Arai H
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Journal Title
J Alzheimers Dis.
Volume: 25
Issue: 3
Pages: 989-1002
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Leucine-rich α2-glycoprotein overexpression in the brain contributes to memory impairment2017
Author(s)
2.Akiba C, Nakajima M, Miyajima M, Ogino I, Miura M, Inoue R, Nakamura E, Kanai F, Tada N, Kunichika M, Yoshida M, Nishimura K, Kondo A, Sugano H, Arai H.
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Journal Title
Neurobiology of Aging
Volume: 60
Pages: 11-19
DOI
Related Report
Peer Reviewed / Open Access
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