Department of Physiology, School of Medicine and Trinity College Institute of Neuroscience, University of Dublin, Trinity College, Dublin, Ireland.
Hippocampus. 2012 Nov;22(11):2127-35. doi: 10.1002/hipo.22033. Epub 2012 May 10.
Consolidation of long-term memory is dependent on synthesis of new proteins in the hippocampus and associated cortical regions. The neurotrophin brain-derived neurotrophic factor (BDNF) is tightly regulated by activity-dependent cellular processes and is strongly linked with mechanisms underlying learning and memory. BDNF activation of tyrosine receptor kinase (TrkB) stimulates intracellular signaling cascades implicated in plasticity, including the extracellular-signal related kinase (ERK)/mitogen-activated protein kinase (MAPK) pathway and the phosphatidylinositide-3-kinase (PI3K)/Akt pathway. Here, we investigate the role of BDNF, ERK/MAPK, and PI3K/AKT signaling cascade in recognition memory in the rat. We report that recognition memory was associated with increased release of BDNF in the dentate gyrus and perirhinal cortex. This was associated with significant increases in p44ERK activation and c-fos expression in the dentate gyrus and PI3K activation and c-fos expression in the perirhinal cortex. Furthermore, both recognition memory and the associated cell signaling events in dentate gyrus and perirhinal cortex were blocked by intraperitoneal injection of the Trk receptor inhibitor tyrphostin AG879. These data are consistent with the hypothesis that BDNF-stimulated intracellular signaling plays a role in consolidation of recognition memory in the rat.
长期记忆的巩固依赖于海马体和相关皮质区域中新蛋白质的合成。神经营养因子脑源性神经营养因子（BDNF）受活性依赖的细胞过程的严格调节，与学习和记忆的相关机制密切相关。BDNF 激活酪氨酸受体激酶（TrkB）刺激细胞内信号级联反应，包括细胞外信号相关激酶（ERK）/丝裂原激活蛋白激酶（MAPK）途径和磷脂酰肌醇 3-激酶（PI3K）/蛋白激酶 B（Akt）途径。在这里，我们研究了 BDNF、ERK/MAPK 和 PI3K/AKT 信号级联在大鼠识别记忆中的作用。我们报告说，识别记忆与齿状回和边缘区 BDNF 的释放增加有关。这与齿状回中 p44ERK 激活和 c-fos 表达的显著增加以及边缘区中 PI3K 激活和 c-fos 表达的增加有关。此外，腹腔注射 Trk 受体抑制剂 tyrphostin AG879 可阻断大鼠齿状回和边缘区的识别记忆和相关细胞信号事件。这些数据与 BDNF 刺激的细胞内信号在大鼠识别记忆的巩固中起作用的假设一致。
