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Title: cAMP对BDNF引起的TrkB受体磷酸化和树突棘密度增加的调控
Author: 季源源
Degree Level: 博士
Issued Date: 2005
Degree Grantor: 中国科学院神经科学研究所
Place of Degree Grantor: 中国科学院神经科学研究所
Supervisor: 冯林音
Keyword: 环腺苷酸 ; 脑源性神经营养因子 ; TrkB受体 ; 树突棘密度 ; 突角后致密带 ; 门控式调节
Alternative Title: Cyclic AMP Controls BDNF-induced TrkB Phosphorylation and Dendritic Spine Formation in Mature Hippocampal Neurons
Abstract: 脑源性神经营养因子(BDNF)的突触活动受到环腺昔酸(cAMP)的门控调节,但是这种调节机制还不清楚。本研究发现,在成熟的海马神经元中,cAMP通过对BDNF的受体TrkB信号通路和该受体蛋白转运的调节进而调控BDNF的功能。cAMP对BDNF引起的TrkB受体磷酸化的调节具有门控式调节的三个典型特征:cAMP的激动剂可增强低浓度BDNF引起的TrkB受体的磷酸化,而cAMP的抑制剂可阻断高浓度BDNF引起的TrkB受体的磷酸化,cAMP本身不能引起TrkB受体的磷酸化。cAMP能够促进TrkB受体向树突棘的转运,转运过程可能是通过促进TrkB受体和突触骨架蛋白PSD-95的结合来实现的。去甲肾上腺素能和多巴胺能的传入分别通过激活去甲肾上腺素能受体和多巴胺能受体而升高海马神经元内cAMP的水平;去甲肾上腺素能和多巴胺能的激动剂也可以促进肠长B受体的磷酸化和向树突棘的转运。研究表明,BDNF对突触后树"突棘密度的长时程作用也受cAMP的门控调节,但是BDNF对神经元一级树突数目的调节并不受cAMP的调控。本研究结果主要阐述了在中枢神经系统中,cAMP调控BDNF突触功能的特殊机制和其门控式调节的分子机理。
English Abstract: Synaptic actions of brain-derived neurotrophic factor (BDNF) are "gated" by cAMP, but the underlying molecular mechanisms remain unclear. Here we report that cAMP regulates BDNF function by modulating TrkB receptor signaling and trafficking in mature hippocampal neurons. cAMP gates TrkB phosphorylation with three characteristic features: BDNF-induced TrkB phosphorylation was attenuated by inhibitors of cAMP signaling, potentiated by cAMP analogs, and activation of cAMP pathway alone had no effect. In addition, cAMP facilitated trafficking of TrkB to dendritic spines, possibly by promoting its interaction with synaptic scaffolding protein PSD-95. Norepinepherinergic and dopaminergic agonists, which elevate intracellular cAMP concentration, also enhance TrkB phosphorylation and its translocation to spines. Long-term modulation of spine density, but not number of primary dendrites, by BDNF was gated by cAMP. These results reveal a specific role of cAMP in controlling BDNF actions in the brain, and provide new insights into the molecular mechanism underlying cAMP gating.
Language: 中文
Content Type: 学位论文
URI: http://ir.sibs.ac.cn/handle/331001/2256
Appears in Collections:神经所(总)_学位论文

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Recommended Citation:
cAMP对BDNF引起的TrkB受体磷酸化和树突棘密度增加的调控.季源源[d].中国科学院神经科学研究所,2005.20-25
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