BDNF and its pro-peptide are stored in presynaptic dense core vesicles in brain neurons.
BDNF and its pro-peptide are stored in presynaptic dense core vesicles in brain neurons.
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DOI：
10.1083/jcb.201201038
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发表时间：
2012-03-19
期刊：
影响因子：
--
通讯作者：
Barde YA
中科院分区：
文献类型：
--
作者：
Dieni S;Matsumoto T;Dekkers M;Rauskolb S;Ionescu MS;Deogracias R;Gundelfinger ED;Kojima M;Nestel S;Frotscher M;Barde YA
与长期建立的神经营养因子功能的逆行模型相比，脑源性神经营养因子在中枢神经系统中的特异性免疫组织化学定位支持突触前定位和顺行功能的替代模型。虽然脑源性神经营养因子（BDNF）调节许多和复杂的生物过程，包括记忆力的保持，其在成熟的中枢神经系统中的极低水平有很大的复杂的尝试可靠localit.Using严格的特异性控制，我们发现，抗体反应与BDNF或其前肽都染色大致密的核心囊泡在兴奋性突触前末梢的成年小鼠海马。这两个部分的丰度都是BDNF原的10倍。缺乏突触后定位在巴松管突变体中得到证实，巴松管突变体是一种具有明显升高的BDNF水平的神经衰弱倾向的小鼠系。这些发现挑战了以前基于培养神经元的研究结论，该结论表明BDNF的合成和释放依赖于树突的活性。相反，它们为BDNF的顺行作用模式提供了超微结构基础，与来自外周神经系统中神经生长因子实验的长期建立的逆行模型形成对比。
Contrasting with the long-established retrograde model for neurotrophin function, specific immunohistochemical localization of brain-derived neurotrophic factor in the central nervous system supports the alternative model of presynaptic localization and anterograde function. Although brain-derived neurotrophic factor (BDNF) regulates numerous and complex biological processes including memory retention, its extremely low levels in the mature central nervous system have greatly complicated attempts to reliably localize it. Using rigorous specificity controls, we found that antibodies reacting either with BDNF or its pro-peptide both stained large dense core vesicles in excitatory presynaptic terminals of the adult mouse hippocampus. Both moieties were ∼10-fold more abundant than pro-BDNF. The lack of postsynaptic localization was confirmed in Bassoon mutants, a seizure-prone mouse line exhibiting markedly elevated levels of BDNF. These findings challenge previous conclusions based on work with cultured neurons, which suggested activity-dependent dendritic synthesis and release of BDNF. They instead provide an ultrastructural basis for an anterograde mode of action of BDNF, contrasting with the long-established retrograde model derived from experiments with nerve growth factor in the peripheral nervous system.
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影响因子：
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