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脑源性神经营养因子(BDNF)通过磷脂酰肌醇-3激酶依赖性途径诱导海马神经元中BDNF和酪氨酸激酶B mRNA的树突靶向。

Brain-derived neurotrophic factor (BDNF) induces dendritic targeting of BDNF and tyrosine kinase B mRNAs in hippocampal neurons through a phosphatidylinositol-3 kinase-dependent pathway.

作者信息

Righi M, Tongiorgi E, Cattaneo A

机构信息

International School for Advanced Studies (ISAS/SISSA), Neuroscience Program, 34014 Trieste, Italy.

出版信息

J Neurosci. 2000 May 1;20(9):3165-74. doi: 10.1523/JNEUROSCI.20-09-03165.2000.

Abstract

This study aims to understand the mechanisms of dendritic targeting of brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) mRNAs. We show that brief depolarizations are sufficient to induce accumulation of BDNF and TrkB mRNAs in dendrites of hippocampal neurons. Endogenous BDNF, secreted during the KCl stimulation, contributes significantly to the dendritic accumulation of BDNF-TrkB mRNAs. In the absence of depolarization, 1 min pulses of exogenous BDNF are sufficient to induce dendritic accumulation of BDNF-TrkB mRNAs. After binding to TrkB, BDNF exerts this action by activating a PI-3 kinase-dependent pathway. The accumulation of dendritic mRNA by BDNF is not mediated by BDNF-induced neurotransmitter release. Because most hippocampal neurons coexpress BDNF and TrkB receptors, these results show that the subcellular distribution of BDNF-TrkB mRNAs is under the control of an autocrine-paracrine BDNF-TrkB-dependent loop.

摘要

本研究旨在了解脑源性神经营养因子(BDNF)和酪氨酸激酶B(TrkB)mRNA树突靶向的机制。我们发现,短暂的去极化足以诱导BDNF和TrkB mRNA在海马神经元树突中的积累。在氯化钾刺激过程中分泌的内源性BDNF对BDNF-TrkB mRNA的树突积累有显著贡献。在没有去极化的情况下,1分钟的外源性BDNF脉冲足以诱导BDNF-TrkB mRNA的树突积累。BDNF与TrkB结合后,通过激活PI-3激酶依赖性途径发挥此作用。BDNF诱导的树突mRNA积累不是由BDNF诱导的神经递质释放介导的。由于大多数海马神经元共表达BDNF和TrkB受体,这些结果表明BDNF-TrkB mRNA的亚细胞分布受自分泌-旁分泌BDNF-TrkB依赖性环路的控制。

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