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Title: TRPC离子通道在脑源性神经营养因子介导的神经元轴突转向过程中的作用
Author: 李艳
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: 蒲慕明
Keyword: 轴突转向 ; TRPC通道
Alternative Title: Essential role of TRPC channels in the guidance of nerve growth cones by brain-derived neurotrophic factor
Abstract: 本实验首次报道了TRPC离子通道在脑源性神经营养因子(BDNF)介导的神经元轴突生长锥转向反应中的重要作用。通过药理学方法阻断TRPC离子通道的活性以及通过电转染的方法在小脑颗粒细胞中表达干扰型小RNA(smaninterferenceRNA,siRNA)或表达失活突变型(dominantnegative,DN)TRPC以降低内源性的TRpC离子通道的活性均可阻断BDNF的浓度梯度对小脑颗粒细胞轴突生长锥的吸引反应。BDNF介导的神经元轴突生长锥的转向反应依赖于细胞内的钙离子(Ca2+)信号。通过药理学方法和表达siRNA降低TRPC离子通道的活性均可降低BDNF在小脑颗粒细胞轴突生长锥内引起的Ca2+信号,从而发现TRPC离子通道是BDNF介导的小脑颗粒细胞轴突转向过程中Ca2+进入的主要通道,揭示了TRPC离子通道在神经系统发育中的重要作用。
English Abstract: Brain-derived neurotrophic factor (BDNF) is known to promote neuronal survival and differentiation and to guide axon extension in vitro and in vivo. The BDNF-induced chemoattraction of axonal growth cones requires Ca2+ signaling, but how Ca2+ at the growth cone is regulated by BDNF remains largely unclear. Extracellular application of BDNF triggers membrane currents resembling that through TRPC (Transient Receptor Potential Canonical) channels in rat pontine neurons and in Xenopus spinal neurons. We here report that in cultured cerebellar granule cells TRPC channels contribute to the BDNF-induced Ca2+ elevation at the growth cone and are required for BDNF-induced chemoattractive turning. Several members of the TRPC family are Mghly expressed in these neurons, and both Ca2+ elevation and growth cone turning induced by BDNF were abolished by pharmacological inhibition of TRPC channels, over-expression of a dominant negative form of TRPC3 or TRPC6, or down-regulation of the expression of TRPC3 with small interference RNA (siRNA). Thus TRPC channel activity is essential for nerve growth cone guidance by BDNF.
Language: 中文
Content Type: 学位论文
URI: http://ir.sibs.ac.cn/handle/331001/2258
Appears in Collections:神经所(总)_学位论文

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Recommended Citation:
TRPC离子通道在脑源性神经营养因子介导的神经元轴突转向过程中的作用.李艳[d].中国科学院神经科学研究所,2005.20-25
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