NMDA受容体は,化学性イシュケミアの際にミエリン内のカルシウム蓄積を媒介する
1Ottawa Health Research Institute, Division of Neuroscience and Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario K1Y 4K9, Canada.
Nature
|December 24, 2005
まとめ
中枢神経系ミエリンは,オリゴデンドロサイトとは独立して,イシュケミア中にカルシウムを蓄積することができる. ミエリン内のN-メチル-d-アスパルテート (NMDA) 受容体は,このカルシウム増加を媒介し,非ミエリン性疾患の新たな治療標的を示唆する.
科学分野:
- 神経科学は神経科学である.
- 細胞生物学 細胞生物学
- ニューロンの変性です.
背景:
- オリゴデンドロサイトによって生成される中枢神経系 (CNS) のミエリンは,迅速な神経衝動伝導に不可欠です.
- 骨髄膜の損傷と喪失は,多くの神経学的疾患の特徴であり,重大な障害につながる.
- ミエリンダメージを誘発するメカニズムは十分に理解されていませんが,しばしばそれがオリゴデンドロサイトの運命を反映していると仮定されています.
研究 の 目的:
- 中枢神経系のミエリン内でのカルシウム蓄積を媒介するN-メチル-d-アスパルテート (NMDA) グルタミン酸受容体の役割を化学性イシュケミア中に調査する.
- ミエリンが有害な刺激に対して独立して反応できるかどうかを判断する.
- 脱ミエリン性疾患の潜在的治療標的を調査する.
主な方法:
- 2フォトン顕微鏡を用いて,成人のラットの視神経におけるカルシウム指標X-rhod-1を画像化しました.
- 様々なNMDAおよびAMPA/カイナート受容体アンタゴニスト (MK-801,7-クロロキヌルン酸,d-AP5,NBQX,NVP-AAM077,イフェンプロジル) を適用しました.
- ミエリン内のNMDA受容体サブユニット (NR1,NR2,NR3) を検出するために,免疫ヒストキミストリーと免疫プレシピテーションを行った.
主要な成果:
- NMDA受容体アンタゴニストは,AMPA/カイナートアンタゴニストは含まないが,イシュケミア誘発のミエリンにおけるカルシウム増加を著しく阻害した.
- NMDA受容体アンタゴニズムは, in vitro ischemiaによって引き起こされるミエリンに対する超構造的損傷を大幅に軽減しました.
- すべての必要なNMDA受容体のサブユニットはミエリンで検出され,機能的受容体の存在を示しました.
結論:
- 成熟したミエリンシート (myelin sheath) は,親オリゴデンドロサイト (parent oligodendrocyte) から独立して,イシュケミアなどの有害な刺激に反応することができる.
- ミエリンシート内に位置するNMDA受容体は,イシュケミアの間にカルシウム蓄積を媒介し,新しいアクソミエリンシグナル伝達経路を表しています.
- ミエリン性NMDA受容体をターゲットにすることは,多発性硬化症や神経外傷のような非ミエリン性疾患に対する潜在的な治療戦略を提供します.
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