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

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
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DOI:
10.1523/jneurosci.20-09-03165.2000
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发表时间:
2000-05-01
影响因子:
5.3
通讯作者:
Cattaneo, A
Cattaneo, A
中科院分区:
医学1区
文献类型:
--
作者:
Righi, M;Tongiorgi, E;Cattaneo, A

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本研究旨在了解脑源性神经营养因子(BDNF)和酪氨酸激酶B(Trk B)mRNA的树突靶向作用机制。我们发现,短暂的去极化足以诱导海马神经元树突中BDNF和TrkB mRNA的积累。KCl刺激过程中分泌的内源性BDNF显著促进了BDNF-TrkB mRNA的树突状积累。在不存在去极化的情况下,外源性BDNF的1分钟脉冲足以诱导BDNF-TrkB mRNA的树突状积累。在与TrkB结合后,BDNF通过激活PI-3激酶依赖性途径发挥这种作用。BDNF诱导的树突状细胞mRNA的积累不是由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,因此这些结果表明BDNF-TrkB mRNA的亚细胞分布受自分泌-旁分泌BDNF-TrkB依赖性环的控制。
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.