Role of brain-derived neurotrophic factor (BDNF) in learning and memory

我们研究了脑源性神经营养因子(BDNF)促进学习和记忆的细胞机制。我们的研究结果表明：(1)8臂放射臂迷宫空间记忆的形成与海马区BDNF及其受体TrkB磷酸化水平的增加有关。(2)侧脑室持续注射反义BDNF寡核苷酸可抑制大鼠的空间记忆获得及记忆保持和/或提取过程。(3)PI3-K/Akt信号通路激活和新的蛋白质合成与BDNF依赖的学习记忆有关。(4)BDNF/TrkB信号与NMDA受体通过src家族酪氨酸激酶Fyn的相互作用对空间记忆的形成也起重要作用。这些结果表明，BDNF分别通过TrkB/PI3-K/Akt和TrkB/Fyn/NR2B信号通路激活新的蛋白质合成和NMDA受体在空间记忆的形成和维持中起关键作用。此外，我们还获得了一些关于空间记忆的神经机制的数据：(1)在放射状臂迷宫中，海马CA3区是空间记忆形成的必需区域。(2)海马区PKA/CREB信号通路的激活在放射臂迷宫的空间记忆形成中起重要作用。(3)利用八臂径向臂迷宫开发了一种新的学习记忆任务，并对其进行了表征。(4)将β-淀粉样蛋白或冈田酸直接注入脑内会导致学习和记忆障碍。

We investigated cellular mechanisms by which brain-derived neurotrophic factor (BDNF) facilitates learning and memory. Our findings indicated that (1) Spatial memory formation in an 8-arm radial arm maze is associated with an increase in the mRNA levels of BDNF and its receptor TrkB phosphorylation in the hippocampus. (2) Continuous intracerebroventricular infusion of antisense BDNF oligonucleotide inhibited the processes of spatial memory acquisition as well as memory retention and/or retrival. (3) Activation of PI3-K/Akt signaling pathway and new protein synthesis is associated with BDNF-dependent learning and memory. (4) Interaction between BDNF/TrkB signaling and NMDA receptors via a src-family tyrosine kinase Fyn is also important for spatial memory formation.These results suggest that BDNF plays a crucial role in spatial memory formation and maintenance by activating new protein synthesis and NMDA receptors in the hippocampus, via TrkB/PI3-K/Akt and TrkB/Fyn/NR2B signaling pathways, respectively.Furthermore, we obtained some data regarding neural mechanism of spatial memory : (1)The CA3 region of the hippocampus is obligatory for spatial memory formation in the radial arm maze. (2) The activation of PKA/CREB signaling pathway in the hippocampus plays an important role in spatial memory formation in the radial arm maze. (3) A novel learning and memory task using an 8-arm radial arm maze was developed and characterized. (4) Direct infusion of p-amyloid or okadaic acid into the brain induces learning and memory impairment.