| Project/Area Number |
16GS0315
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| Research Category |
Grant-in-Aid for Creative Scientific Research
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| Allocation Type | Single-year Grants |
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| Research Institution | Juntendo University (2008)
Osaka University (2004-2007) |
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Principal Investigator |
UCHIYAMA Yasuo Juntendo University, 医学部, 教授 (10049091)
|
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| Co-Investigator(Kenkyū-buntansha) |
WAGURI Satoshi 福島県立医科大学, 医学部, 教授 (30244908)
SHIBATA Masahiro 新潟大学, 医歯学系, 准教授 (10343253)
KOIKE Masato 順天堂大学, 医学部, 准教授 (80347210)
佐々木 光穂 順天堂大学, 医学部, 助教 (20432536)
上野 隆 順天堂大学, 医学部, 准教授 (10053373)
後藤 邦仁 大阪大学, 医学系研究科, 助手 (10362716)
谷田 以誠 順天堂大学, 医学部, 講師 (30296868)
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| Project Period (FY) |
2004 – 2008
|
| Project Status |
Completed (Fiscal Year 2008)
|
| Budget Amount *help |
¥481,390,000 (Direct Cost: ¥370,300,000、Indirect Cost: ¥111,090,000)
Fiscal Year 2008: ¥72,280,000 (Direct Cost: ¥55,600,000、Indirect Cost: ¥16,680,000)
Fiscal Year 2007: ¥81,120,000 (Direct Cost: ¥62,400,000、Indirect Cost: ¥18,720,000)
Fiscal Year 2006: ¥106,860,000 (Direct Cost: ¥82,200,000、Indirect Cost: ¥24,660,000)
Fiscal Year 2005: ¥109,590,000 (Direct Cost: ¥84,300,000、Indirect Cost: ¥25,290,000)
Fiscal Year 2004: ¥111,540,000 (Direct Cost: ¥85,800,000、Indirect Cost: ¥25,740,000)
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| Keywords | オートファジー / 神経細胞 / リソソーム / カテプシン / 脳虚血 / オートファジー性神経細胞死 / 低酸素-脳虚血 / Atg7 / LC3 / ミュータントマウス / リソソームプロテアーゼ / 脂肪代謝 / 低酸素脳虚血傷害 / LC3欠損マウス / Atg7欠損マウス / カテプシンB / カテプシンL / カテプシンD / 細胞死 / ノックアウトマウス / 神経細胞死 / オートファゴソーム / プロテアーゼ / Atg7-KOマウス / ユビキチン / 低酸素能虚血負荷 / 海馬CA1錘体細胞死 / RNAi / DNAマイクロアレイ |
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| Research Abstract |
Hypoxia/ischemia (H/I) brain injury at birth is an important cause of cerebral palsy, mental retardation, and epilepsy. The H/I insult also causes energy failure, oxidative stress, and unbalanced ion fluxes, leading to high induction of autopahgy in brain neurons. Induction of neuronal autophagy after H/I injury is generally considered neuroprotective, as it maintains cellular homeostasis. However, our recent results show that cell death of hippocampal pyramidal neurons following neonatal H/I injury is largely prevented by Atg7 deficiency. This is the first report that we are aware of providing direct evidence for autophagy-induced neuron death after neonatal mouse H/I brain injury, using mice that cannot execute autophagy specifically in CNS tissue. Thus, therapeutic strategies to inhibit autophagy-induced neuron death may prove beneficial in the treatment of both pediatric and adult H/I brain injury.
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