Brain-derived neurotrophic factor promotes long-term potentiation-related cytoskeletal changes in adult hippocampus
Brain-derived neurotrophic factor promotes long-term potentiation-related cytoskeletal changes in adult hippocampus
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DOI：
10.1523/jneurosci.4037-06.2007
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发表时间：
2007-03-14
影响因子：
5.3
通讯作者：
Lynch, Gary
中科院分区：
文献类型：
--
作者：
Rex, Christopher S.;Lin, Ching-Yi;Lynch, Gary
脑源性神经营养因子（BDNF）是一种非常有效的，正调节的θ波爆发诱导的长时程增强（LTP）在成人海马。目前的研究测试了神经营养因子是否通过促进树突棘细胞骨架的变化来发挥其作用。当BDNF单独作用于大鼠海马切片时，没有引起丝状肌动蛋白（F-actin）的阳鞘素标记的变化，但显著增加了由θ波爆发刺激阈值水平产生的密集标记的棘的数量。相反，BDNF清道夫TrkB-Fc完全阻断了阈值以上θ刺激水平产生的脊柱f -肌动蛋白的增加。TrkB-Fc在θ波后1 - 2分钟阻滞LTP巩固，而不是10分钟。进一步的实验证实，p21活化激酶和cofilin这两种参与脊柱形态发生的肌动蛋白调节蛋白在成熟海马的脊柱中集中，并进一步表明，在输注BDNF后，两者都发生了快速的、剂量依赖性的磷酸化。这些结果表明，BDNF对肌动蛋白细胞骨架的影响一直保留到成年期，在成年期，它起到积极调节时间依赖性LTP巩固过程的作用。
Brain-derived neurotrophic factor (BDNF) is an extremely potent, positive modulator of theta burst induced long-term potentiation (LTP) in the adult hippocampus. The present studies tested whether the neurotrophin exerts its effects by facilitating cytoskeletal changes in dendritic spines. BDNF caused no changes in phalloidin labeling of filamentous actin (F-actin) when applied alone to rat hippocampal slices but markedly enhanced the number of densely labeled spines produced by a threshold level of theta burst stimulation. Conversely, the BDNF scavenger TrkB-Fc completely blocked increases in spine F-actin produced by suprathreshold levels of theta stimulation. TrkB-Fc also blocked LTP consolidation when applied 1 - 2 min, but not 10 min, after theta trains. Additional experiments confirmed that p21 activated kinase and cofilin, two actin-regulatory proteins implicated in spine morphogenesis, are concentrated in spines in mature hippocampus and further showed that both undergo rapid, dose-dependent phosphorylation after infusion of BDNF. These results demonstrate that the influence of BDNF on the actin cytoskeleton is retained into adulthood in which it serves to positively modulate the time-dependent LTP consolidation process.