発達中の皮質内ニューロンの内在的に決定された細胞死
Derek G Southwell1, Mercedes F Paredes, Rui P Galvao
1Neuroscience Graduate Program, University of California, San Francisco, California 94143, USA. dereksouthwell@gmail.com
Nature
|October 9, 2012
まとめ
皮質内ニューロンの数は,外部信号ではなく,内在的要因によって決定されます. この γ-アミノバター酸 (GABA) を分泌するニューロンの約40%は,発達中にプログラム細胞死を経験します.
科学分野:
- 神経科学は神経科学である.
- 発達生物学 発達生物学について
- 細胞生物学 細胞生物学
背景:
- 皮質の阻害回路は,腹前頭脳から発生するγ-アミノバター酸 (GABA) を分泌する内ニューロンに依存しています.
- 皮質内ニューロンの最終数を決定するメカニズムは,その遠い発達起源にもかかわらず,依然として不明確です.
- ニューロトロフィック仮説は,過剰生産と,その後,外部トロフィック信号の競争を通じて排除することを示唆しています.
研究 の 目的:
- ネズミの皮質内神経細胞の発達細胞死を調査する.
- インターニューロンの生存が,外的なトロフィック要因または内的なメカニズムによって調節されているかどうかを判断する.
- インターニューロン生存と集団調節におけるバックスとTrkBの役割を調査する.
主な方法:
- マウスの皮質内ニューロン発達のインビボおよびインビトロ研究.
- 異なった条件下で生存率と細胞死亡率を評価するための移植実験.
- バックス依存アポトーシスとTrkBシグナル伝達経路の分析.
主要な成果:
- 発達中の皮質内ニューロンの約40%は,産後バックス依存性アポトーシスを経験する.
- 大脳皮質に移植された,またはインビトロ培養されたインターニューロン前駆体は,発達的に似た時期に細胞死を示した.
- 細胞死亡率は200倍もの移植サイズの範囲で一定であり,TrkBの破壊の影響を受けませんでした.
- 移植はインターニューロン数を増加させましたが,抑制シナプスイベントの頻度は比例して増加しませんでした.
結論:
- 皮質内ニューロンの細胞死は,細胞自律的に,または集団レベルの内ニューロン間の競争によって内在的に決定されるようです.
- 外的なトロフィック信号は,内部ニューロンの生存の主要な調節因子ではないようです.
- この発見は,内部神経細胞の集団制御に関する従来の神経栄養的仮説に異議を唱えている.
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