Heparin-binding EGF-like growth factor is required for synaptic plasticity and memory formation
Heparin-binding EGF-like growth factor is required for synaptic plasticity and memory formation
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DOI：
10.1016/j.brainres.2011.09.003
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发表时间：
2011-10-24
期刊：
影响因子：
2.9
通讯作者：
Hara, Hideaki
中科院分区：
文献类型：
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作者：
Oyagi, Atsushi;Moriguchi, Shigeki;Hara, Hideaki
肝素结合型表皮生长因子样生长因子（HB-EGF）是表皮生长因子（EGF）家族成员之一，是多种类型细胞的强效有丝分裂肽。HB-EGF广泛表达于中枢神经系统，包括海马和大脑皮层，被认为在发育和成人神经系统中起关键作用。在这项研究中，我们通过在两种不同的学习任务中测试HB-EGF条件敲除小鼠（KO）来评估HB-EGF在学习和记忆中的作用，并评估这些小鼠海马切片的长期增强（LTP）。HB-EGF KO小鼠在Morris水迷宫中的空间记忆和被动回避实验中的恐惧学习均受到损害。HB-EGF KO小鼠也显示LTP受损，Ca(2+)/钙调素依赖性蛋白激酶II （CaMKII）和磷酸化GluR1活性降低。我们还发现，在HB-EGF KO小鼠中，神经生长因子（NGF）、脑源性神经营养因子（BDNF）、神经营养因子-3 （NT-3）或胶质细胞系源性神经营养因子（GDNF）等神经营养因子的水平在几个脑区域发生了改变。这些结果证实了HB-EGF在突触可塑性和记忆形成中的重要性。(C) 2011 Elsevier B.V.版权所有
Heparin-binding epidermal growth factor-like growth factor (HB-EGF), a member of epidermal growth factor (EGF) family, is a potent mitogenic peptide for various types of cells. HB-EGF is widely expressed in central nervous system, including hippocampus and cerebral cortex, and is considered to play pivotal roles in the developing and adult nervous system. In this study, we assessed the role of HB-EGF in learning and memory by testing HB-EGF conditional knock-out mice (KO) in two different learning tasks, and evaluated the long-term potentiation (LTP) in hippocampus slices from these mice. The HB-EGF KO mice were impaired in spatial memory in the Morris water maze and in fear learning in a passive avoidance test. HB-EGF KO mice also showed an impaired LTP, and reduction in activity of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and phosphorylated GluR1. We also found that the levels of neurotrophic factors, such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), or glial cell line-derived neurotrophic factor (GDNF), were altered in several brain regions in the HB-EGF KO mice. These results confirm the importance of the HB-EGF in synaptic plasticity and memory formation. (C) 2011 Elsevier B.V. All rights reserved.