Rex Christopher S, Lin Ching-Yi, Kramár Eniko A, Chen Lulu Y, Gall Christine M, Lynch Gary
Department of Neurobiology and Behavior, University of California, Irvine, Irvine, California 92697-4292, USA.
J Neurosci. 2007 Mar 14;27(11):3017-29. doi: 10.1523/JNEUROSCI.4037-06.2007.
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.
脑源性神经营养因子（BDNF）是成年海马体中对theta爆发诱导的长时程增强（LTP）极具效力的正向调节剂。本研究检测了这种神经营养因子是否通过促进树突棘的细胞骨架变化来发挥其作用。单独应用于大鼠海马切片时，BDNF对丝状肌动蛋白（F-肌动蛋白）的鬼笔环肽标记没有影响，但显著增加了由阈值水平的theta爆发刺激产生的密集标记棘突的数量。相反，BDNF清除剂TrkB-Fc完全阻断了由超阈值水平的theta刺激产生的棘突F-肌动蛋白的增加。当在theta序列刺激后1-2分钟（而非10分钟）应用TrkB-Fc时，它也阻断了LTP巩固。额外的实验证实，参与棘突形态发生的两种肌动蛋白调节蛋白p21活化激酶和丝切蛋白在成熟海马体的棘突中聚集，并且进一步表明，在注入BDNF后，两者都经历快速的、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在成年期依然存在，在其中它起到正向调节时间依赖性LTP巩固过程的作用。
