ヒッポキャンプスの長期的な増強は,チロシンキナーゼ阻害剤によって阻害されます
T J O'Dell1, E R Kandel, S G Grant
1Center for Neurobiology and Behavior, College of Physicians and Surgeons of Columbia University, New York, New York 10032.
Nature
|October 10, 1991
まとめ
タイロシンキナーゼの活動は,記憶形成に不可欠なプロセスであるヒポキャンパスにおける長期増強 (LTP) を誘発するために重要である. 特定の阻害剤はLTP誘導を阻害し,シナプス性可塑性におけるチロシンキナーゼの役割を示唆した.
科学分野:
- 神経科学は神経科学である.
- 分子生物学は分子生物学である.
- バイオケミストリー バイオケミストリー
背景:
- ヒポキャンパスにおける長期増強 (LTP) は,記憶形成の基礎となる重要な細胞機構である.
- CA1領域のLTPには,NMDA受容体に依存したカルシウム流入とセリン/スレオニンキナーゼの活性化が必要です.
- タンパク質チロシンキナーゼは,学習と記憶に関与する領域である海馬に豊富に存在します.
研究 の 目的:
- ヒポキャンパスのLTPにおけるチロシンキナーゼ活性に対する潜在的な要求を調査する.
- ティロシンキナーゼがセリン/スレオニンキナーゼを超えてシナプス可塑性において役割を果たすかどうかを判断する.
主な方法:
- ヒポキャンパスのチロシンキナーゼとセリン/スレオニンキナーゼ (PKA,PKC,CaMKII) に対する特異性について5つのチロシンキナーゼ阻害剤をスクリーニングした.
- 特定の阻害剤として特定されたラベンデスティンAとジェニステインを使用して,LTP誘導と維持に対する効果をテストしました.
- 入浴用およびポストシナプス注射による阻害剤の投与.
主要な成果:
- ラヴェンダスティンAとジェニステインは,海馬におけるチロシンキナーゼ活性を選択的に抑制した.
- これらの特定の阻害剤は,LTPの誘導を阻害したが,確立したLTPには影響を及ぼさなかった.
- 阻害剤は,正常なシナプス伝達や,PKAやPKCによって媒介される神経伝達物質の作用に影響を及ぼさなかった.
結論:
- タイロシンキナーゼの活性性は,海馬における長期的増強を誘導するために,ポストシナプス的に必要である.
- タイロシンキナーゼは,シナプス可塑性においてセリンとスレオニンキナーゼ (CaMKII,PKC) と並行して,ポストシナプスキナーゼネットワーク内で機能する可能性があります.
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