Signaling mechanisms mediating BDNF modulation of memory formation in vivo in the hippocampus
Signaling mechanisms mediating BDNF modulation of memory formation in vivo in the hippocampus
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DOI：
10.1023/a:1021848706159
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发表时间：
2002-12-01
影响因子：
4
通讯作者：
Medina, JH
中科院分区：
文献类型：
--
作者：
Alonso, M;Vianna, MRM;Medina, JH
鉴于脑源性神经营养因子（BDNF）调节短期突触功能和活动依赖性突触可塑性在成年海马，在这里，我们研究了在体内海马介导的长期记忆（LTM）形成的一个审判恐惧动机的学习任务的BDNF调制的信号传导机制。将功能阻断性抗BDNF抗体注入背侧海马CA 1区，可降低细胞外信号调节激酶2（ERK 2）和CREB的激活，并损害LTM保留评分。通过PD 098059抑制ERK 1/2活化产生类似的效果，并且还减少CREB磷酸化。相反，海马内给予重组人BDNF增加ERK 1/2和CREB激活，促进LTM。激活p38，激活PKC亚型，激活AKT后BDNF或抗BDNF输注不变。此外，在细胞核样品中未发现α PKA和β PKA催化亚基的变化。因此，我们的研究结果表明，BDNF发挥其作用，在海马CA 1区的LTM形成在体内，至少部分，通过CREB激活。此外，BDNF诱导的CREB激活似乎主要通过ERK 1/2信号通路的激活来介导。
Given that brain-derived neutrophic factor (BDNF) modulates both short-term synaptic function and activity-dependent synaptic plasticity in the adult hippocampus, here we examined signaling mechanisms in vivo in the hippocampus mediating BDNF modulation of long-term memory (LTM) formation of a one-trial fear-motivated learning task in rats. Bilateral infusions of function-blocking anti-BDNF antibody into the CA1 region of the dorsal hippocampus decreased extracellular-signal regulated kinase 2 (ERK2) and CREB activation and impaired LTM retention scores. Inhibition of ERK1/2 activation by PD098059 produced similar effects and also reduced CREB phosphorylation. In contrast, intrahippocampal administration of recombinant human BDNF increased ERK1/2 and CREB activation and facilitated LTM. Activated-p38, activated-PKC isoforms, and activated-AKT were unaltered after BDNF or anti-BDNF infusion. In addition, no changes were found on alphaPKA and betaPKA catalytic subunits in nuclear samples. Thus, our results suggest that BDNF exerts its role in LTM formation in vivo in CA1 region of the hippocampus, at least in part, via CREB activation. Moreover, BDNF-induced CREB activation appears to be mediated mainly through the activation of ERK1/2 signaling pathway.