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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Reversible modulations of neuronal plasticity by VEGF
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Reversible modulations of neuronal plasticity by VEGF

机译：VEGF对神经元可塑性的可逆调节

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摘要

Neurons, astrocytes, and blood vessels are organized in functional "neurovascular units" in which the vasculature can impact neuronal activity and, in turn, dynamically adjust to its change. Here we explored different mechanisms by which VEGF, a pleiotropic factor known to possess multiple activities vis-a-vis blood vessels and neurons, may affect adult neurogenesis and cognition. Conditional transgenic systems were used to reversibly overexpress VEGF or block endogenous VEGF in the hippocampus of adult mice. Importantly, this was done in settings that allowed the uncoupling of VEGF-promoted angiogenesis, neurogenesis, and memory. VEGF overexpression was found to augment all three processes, whereas VEGF blockade impaired memory without reducing hippocampal perfusion or neurogenesis. Pertinent to the general debate regarding the relative contribution of adult neurogenesis to memory, we found that memory gain by VEGF overexpression and memory impairment by VEGF blockade were already evident at early time points at which newly added neurons could not yet have become functional. Surprisingly, VEGF induction markedly increased in vivo long-term potentiation (LTP) responses in the dentate gyrus, and VEGF blockade completely abrogated LTP. Switching off ectopic VEGF production resulted in a return to a normal memory and LTP, indicating that ongoing VEGF is required to maintain increased plasticity. In summary, the study not only uncovered a surprising role for VEGF in neuronal plasticity, but also suggests that improved memory by VEGF is primarily a result of increasing plasticity of mature neurons rather than the contribution of newly added hippocampal neurons.
机译：神经元，星形胶质细胞和血管组织在功能性“神经血管单位”中，其中的脉管系统可以影响神经元的活动，进而动态地适应其变化。在这里，我们探讨了不同的机制，VEGF是一种已知的多效性因子，相对于血管和神经元具有多种活性，可以影响成人的神经发生和认知。条件转基因系统用于成年小鼠海马中可逆性过表达VEGF或阻断内源性VEGF。重要的是，这是在允许VEGF促进的血管生成，神经发生和记忆解偶联的环境中完成的。发现VEGF过度表达增强了所有三个过程，而VEGF阻断在不减少海马灌注或神经发生的情况下损害了记忆。与有关成人神经发生对记忆的相对贡献的一般性辩论有关，我们发现在新添加的神经元尚未发挥功能的早期时间点，VEGF过度表达引起的记忆增加和VEGF阻断引起的记忆障碍已经很明显。出人意料的是，VEGF诱导显着增加了齿状回体内的体内长期增强（LTP）反应，并且VEGF阻断完全消除了LTP。关闭异位VEGF的产生导致恢复正常的记忆力和LTP，表明需要持续的VEGF来维持增加的可塑性。总而言之，该研究不仅揭示了VEGF在神经元可塑性中的令人惊讶的作用，而且表明VEGF改善的记忆力主要是增加成熟神经元的可塑性而不是新添加的海马神经元的贡献。

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    Tamar Licht; Inbal Goshen; Avi Avital; Tirzah Kreisel; Salman Zubedat; Ronen Eavri; Menahem Segal; Ra2 Yirmiya; Eli Keshet;

  • 作者单位

    Deparment of Developmental Biology and Cancer Research, Hebrew University Hadassah Medical School, Jerusalem 91120, Israel;

    Department of Psychology, Hebrew University, Jerusalem 91905, Israel;

    Department of Psychology and Center for Psychobiological Research, Yezreel Valley College,Emek Yezreel 19300, Israel,Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel;

    Department of Psychology, Hebrew University, Jerusalem 91905, Israel;

    Department of Psychology and Center for Psychobiological Research, Yezreel Valley College,Emek Yezreel 19300, Israel;

    Deparment of Developmental Biology and Cancer Research, Hebrew University Hadassah Medical School, Jerusalem 91120, Israel;

    Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel;

    Department of Psychology, Hebrew University, Jerusalem 91905, Israel;

    Deparment of Developmental Biology and Cancer Research, Hebrew University Hadassah Medical School, Jerusalem 91120, Israel;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    vascular biology; neural stem cells; learning;

    机译：血管生物学;神经干细胞;学习;

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