神經(jīng)元的存活對神經(jīng)系統(tǒng)發(fā)育,、神經(jīng)系統(tǒng)疾病發(fā)生及發(fā)展都十分重要,。TRP通道是一類非選擇性的陽離子通道，可以影響從痛覺到雄性生殖等多方面的生理功能,。TRPC通道是TRP通道的一個亞家族,，可被與磷脂酶C偶聯(lián)的受體(如腦源性神經(jīng)生長因子BDNF)激活。上海生命科學研究院神經(jīng)科學研究所王以政研究員帶領其研究組歷經(jīng)近4年的研究,，發(fā)現(xiàn)：TRPC通道對于保護小腦顆粒神經(jīng)元的存活十分重要,，BDNF通過TRPC3和TRPC6通道促進小腦顆粒細胞的存活。該研究組的博士生賈宜昌和周健等,，通過研究TRPC3和TRPC6對于維持小腦發(fā)育過程中正常數(shù)量顆粒細胞存活的作用,，發(fā)現(xiàn)如果增加細胞中該通道的數(shù)量，將有效防止小腦顆粒神經(jīng)元的死亡,，保護小腦顆粒細胞的存活,，而減少該通道的量則作用相反。研究還發(fā)現(xiàn)BDNF激活TRPC3和TRPC6通道,，可提高細胞內(nèi)鈣水平,，從而促進小腦顆粒細胞的存活。該研究結(jié)果揭示了TRPC通道對于神經(jīng)元存活的重要作用,，為理解神經(jīng)元的存活提供了新的思路,。
此項研究成果2007年4月1日在線發(fā)表在Nature Neuroscience雜志上。
保護腦內(nèi)神經(jīng)細胞的,，是一類特殊的“離子通道”,。4月3日從中科院上海生命科學研究院神經(jīng)科學研究所獲悉，王以政研究組歷經(jīng)近4年努力取得相關研究成果,，已在線發(fā)表于本月首期國際著名期刊《自然·神經(jīng)科學》上。
研究發(fā)現(xiàn),，腦內(nèi)名為“TRP”的離子通道可影響從痛覺到雄性生殖等方面的生理功能,，其中有一條“支路”———TRPC通道，對于保護小腦顆粒神經(jīng)細胞的存活十分重要,?？蒲腥藛T進一步發(fā)現(xiàn)，這條“支路”還由幾條“小路”組成，其中第3號和第6號“小路”,，在小腦發(fā)育過程中發(fā)揮著維持正常數(shù)量顆粒細胞存活的作用,，如增加這些通道的數(shù)量，將有效防止小腦顆粒神經(jīng)細胞死亡,。同時,，一些神經(jīng)生長因子會激活這兩條小通道，提高腦細胞內(nèi)鈣水平,，促進其存活,。
部分英文原文：
Published online: 1 April 2007; | doi:10.1038/nn1870
TRPC channels promote cerebellar granule neuron survival
Yichang Jia1, 2, 3, Jian Zhou1, 2, 3, Yilin Tai1, 2 & Yizheng Wang1
1 Laboratory of Neural Signal Transduction, Institute of Neuroscience, Shanghai Institutes of Biological Sciences, Key Laboratory of Neurobiology, Shanghai 200031, China.
2 The Graduate School, Chinese Academy of Science, 320 Yue Yang Road, Shanghai 200031, China.
3 These authors contributed equally to this work.
Correspondence should be addressed to Yizheng Wang [email protected]
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, BDNF-triggered 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.
