海马神经元循环利用脑源性神经营因子以进行活动依赖型分泌和长时程增强维持。
Hippocampal neurons recycle BDNF for activity-dependent secretion and LTP maintenance.
作者信息
Santi Spartaco, Cappello Silvia, Riccio Massimo, Bergami Matteo, Aicardi Giorgio, Schenk Ursula, Matteoli Michela, Canossa Marco
机构信息
CNR-ITOI/ISMN, Bologna, Italy.
出版信息
EMBO J. 2006 Sep 20;25(18):4372-80. doi: 10.1038/sj.emboj.7601303. Epub 2006 Sep 7.
Abstract
Regulation of brain-derived neurotrophic factor (BDNF) secretion plays a critical role in long-term potentiation (LTP). It is generally thought that the supply for this secretion is newly synthesized BDNF targeted to the synapse. Here we provide evidence that hippocampal neurons additionally recycle BDNF for activity-dependent secretion. Exogenously applied BDNF is internalized by cultured neurons and rapidly becomes available for activity-dependent secretion, which is controlled by the same mechanisms that regulate the secretion of newly synthesized BDNF. Moreover, BDNF recycling replaced the new synthesis pathway in mediating the maintenance of LTP in hippocampal slices: the late phase LTP, which is abolished by protein synthesis inhibition, was rescued in slices preincubated with BDNF. Thus, endocytosed BDNF is fed back to the activity-dependent releasable pool required for LTP maintenance.
摘要
脑源性神经营养因子（BDNF）分泌的调节在长时程增强（LTP）中起着关键作用。一般认为，这种分泌的供应是靶向突触的新合成的BDNF。在这里，我们提供证据表明，海马神经元还会回收BDNF用于依赖活动的分泌。外源性应用的BDNF被培养的神经元内化，并迅速可用于依赖活动的分泌，其受调控新合成BDNF分泌的相同机制控制。此外，BDNF回收在介导海马切片中LTP的维持方面取代了新合成途径：蛋白质合成抑制可消除的晚期LTP，在用BDNF预孵育的切片中得以挽救。因此，内吞的BDNF被反馈到LTP维持所需的依赖活动的可释放池中。
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本文引用的文献
1
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Neuron. 2005 Oct 6;48(1):123-37. doi: 10.1016/j.neuron.2005.09.005.
2
Cell-specific expression of the epm1 (cystatin B) gene in developing rat cerebellum.大鼠小脑发育过程中epm1（胱抑素B）基因的细胞特异性表达。
Neurobiol Dis. 2005 Oct;20(1):104-14. doi: 10.1016/j.nbd.2005.02.012.
3
BDNF function in adult synaptic plasticity: the synaptic consolidation hypothesis.脑源性神经营养因子在成体突触可塑性中的作用：突触巩固假说
Prog Neurobiol. 2005 Jun;76(2):99-125. doi: 10.1016/j.pneurobio.2005.06.003.
4
The yin and yang of neurotrophin action.神经营养因子作用的阴阳学说。
Nat Rev Neurosci. 2005 Aug;6(8):603-14. doi: 10.1038/nrn1726.
5
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Mol Cell Neurosci. 2005 May;29(1):11-25. doi: 10.1016/j.mcn.2005.02.004.
6
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7
Induction of long-term potentiation and depression is reflected by corresponding changes in secretion of endogenous brain-derived neurotrophic factor.长期增强和抑制的诱导通过内源性脑源性神经营养因子分泌的相应变化得以体现。
Proc Natl Acad Sci U S A. 2004 Nov 2;101(44):15788-92. doi: 10.1073/pnas.0406960101. Epub 2004 Oct 25.
8
Cleavage of proBDNF by tPA/plasmin is essential for long-term hippocampal plasticity.组织型纤溶酶原激活物/纤溶酶对脑源性神经营养因子前体的切割对于海马体的长期可塑性至关重要。
Science. 2004 Oct 15;306(5695):487-91. doi: 10.1126/science.1100135.
9
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J Neurosci. 2004 Aug 18;24(33):7366-77. doi: 10.1523/JNEUROSCI.1739-04.2004.
10
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J Neurosci. 2004 May 5;24(18):4401-11. doi: 10.1523/JNEUROSCI.0348-04.2004.
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