长期抑郁症和AMPA受体内部化需要通过线粒体激活卡斯巴-3
Zheng Li1, Jihoon Jo, Jie-Min Jia
1The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. lizheng2@mail.nih.gov
Cell
|June 1, 2010
概括
线粒体酶-3激活对长期抑郁症 (LTD) 和神经元中的AMPA受体去除至关重要. 这种亡途径对于突触可塑性至关重要,而不会导致细胞死亡.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 突触可塑性,包括长期抑郁症 (LTD),对大脑功能至关重要.
- LTD涉及AMPA受体的去除,但其分子驱动因素尚未完全理解.
研究的目的:
- 调查在LTD期间AMPA受体内部化背后的分子机制.
- 确定与亡相关的蛋白质在突触可塑性中的作用.
主要方法:
- 使用了caspase-3和-9的抑制剂.
- 产生并研究了caspase-3淘汰赛小鼠.
- 过度表达的抗亡蛋白 (XIAP,Bcl-xL) 和一个突变的Akt1蛋白.
- 在海马神经元和切片中检查了NMDA受体刺激.
主要成果:
- 由线粒体启动的卡斯帕酶-3激活是LTD和AMPA受体内部化所需的.
- 抑制酶-3或-9阻断了LTD和受体的去除.
- 在caspase-3淘汰赛小鼠中,LTD被废除,而LTP没有受到影响.
- 过度表达XIAP,Bcl-xL或一种抗卡斯巴酶的Akt1阻止了LTD.
- 刺激NMDA受体可以在树突中激活caspase-3,而不会诱导亡.
结论:
- 线粒体的caspase-3激活是驱动LTD的一个关键分子机制.
- 亡途径的分子机械意外地参与了突触可塑性.
- 卡斯巴酶-3在Ltd.期间对AMPA受体贩运的调节中发挥着关键作用.
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