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Title: 1.TRPC 通道对兴奋性突触发育的重要作用2.TRPC通道促进小脑颗粒细胞存活
Author: 周健
Degree Level: 博士
Issued Date: 2008-01-09
Degree Grantor: 中国科学院上海生命科学研究院
Place of Degree Grantor: 上海生命科学研究院
Supervisor: 王以政
Keyword: TRPC通道 ; 脑源神经营养因子 ; 小脑颗粒细胞 ; 存活
Alternative Title: TRPC channels promote cerebellar granular neuron survival
Major: 神经生物学
Abstract: TRP通道介导许多生理学的功能。我们的结果报道TRPC亚家族成员TRPC3或TRPC6对血清剥夺(serum-deprivation,SD)引起的小脑颗粒细胞(cerebellar granular neuron,CGN)凋亡有保护作用,同时在整体动物水平促进CGN存活。在体外培养的CGN中,用药物阻断TRPC通道或利用RNAi下调TRPC3或TRPC6的表达,可以减弱BDNF对CGN的保护作用,以及BDNF引起的CGN胞内钙离子水平的上调和ERK和CREB的磷酸化。同时,过量表达TRPC3或TRPC6增加CREB磷酸化和转录活性增加,防止血清剥夺引发的CGN死亡,而这种保护作用可以被突变型的CREB所阻断。当阻断或者特异性敲减激活TRPC通道的上游信号PLC或IP3R时,均可以抑制BDNF的保护作用。在新生大鼠小脑上,用RNAi敲减TRPC3或TRPC6可以引起新生大鼠CGN死亡,而这一作用可以被同时过量表达野生型TRPC3或TRPC6所挽回。因此,我们提供的体内和体外证据都证实 TRPC3或TRPC6 促进小脑颗粒细胞的存活,这一发现对于认识神经系统中TRPC通道的功能有着重要意义。
English Abstract: Channels formed by the transient receptor potential (TRP) family of proteins have a variety of physiological functions. Here we report that two members of the TRP cation channel (TRPC) subfamily, TRPC3 and 6, protected cerebellar granule neurons (CGNs) against serum deprivation–induced cell death in cultures and promoted CGN survival in rat brain. In CGN cultures, blocking TRPC channels or downregulating TRPC3 or 6 suppressed brain-derived neurotrophic factor (BDNF)–mediated protection, BDNFtriggered intracellular Ca2+ elevation and BDNF-induced CREB activation. By contrast, overexpressing TRPC3 or 6 increased CREB-dependent reporter gene transcription and prevented apoptosis in the neurons deprived of serum, and this protection was blocked by the dominant negative form of CREB. Furthermore, downregulating TRPC3 or 6 induced CGN apoptosis in neonatal rat cerebellum, and this effect was rescued by overexpressing either TRPC3 or 6. Thus, our findings provide in vitro and in vivo evidence that TRPC channels are important in promoting neuronal survival.
Language: 中文
Content Type: 学位论文
URI: http://ir.sibs.ac.cn/handle/331001/2375
Appears in Collections:神经所(总)_学位论文

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Recommended Citation:
1.TRPC 通道对兴奋性突触发育的重要作用2.TRPC通道促进小脑颗粒细胞存活.周健[d].中国科学院上海生命科学研究院,2008.20-25
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