发育中的皮层内核神经元的内在决定的细胞死亡
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
概括
皮层内部神经元的数量是由内在因素决定的,而不是外部信号. 大约40%的这些 secret-aminobutyric acid (GABA) 分泌神经元在发育过程中经历了编程细胞死亡.
科学领域:
- 神经科学是一个神经科学.
- 发展生物学 发展生物学
- 细胞生物学 细胞生物学
背景情况:
- 皮层抑制电路依赖于来自腹前脑的γ-aminobutyric acid (GABA) 分泌内部神经元.
- 确定皮层内神经元最终数量的机制,尽管它们的发育起源很远,但仍然不清楚.
- 神经营养假设表明,通过对外部营养信号的竞争,过度生产和随后的消除.
研究的目的:
- 为了研究小鼠皮质内神经元的发育细胞死亡.
- 为了确定内部神经元的存活是否受到外部热量因素或内在机制的调节.
- 探索巴克斯和TrkB在内部神经元生存和人口调节中的作用.
主要方法:
- 在体内和体外研究小鼠皮层内部神经元发育.
- 移植实验用于在不同条件下评估细胞存活率和细胞死亡.
- 对依赖巴克斯的亡和TrkB信号通路的分析.
主要成果:
- 大约40%的发育中的皮层内部神经元在出生后经历了巴克斯依赖性亡.
- 移植到皮层或在体外培养的内部神经元前体在发育上相似的时间表现出细胞死亡.
- 细胞死亡率在200倍的移植大小范围内保持不变,并不受TrkB破坏的影响.
- 移植增加了内部神经元的数量,但并没有相应地增加抑制突触事件的频率.
结论:
- 皮层内部神经元的细胞死亡似乎是从本质上决定的,要么是细胞自主,要么是通过内部神经元之间的人口级别竞争.
- 外在的营养信号似乎不是内部神经元存活的主要调节者.
- 这些发现挑战了内部神经元人口控制的传统神经营养假设.
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