Heparin-binding EGF-like growth factor is required for synaptic plasticity and memory formation

Atsushi Oyagi, Shigeki Moriguchi, Atsumi Nitta, Kenta Murata, Yasuhisa Oida, Kazuhiro Tsuruma, Masamitsu Shimazawa, Kohji Fukunaga, Hideaki Hara

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)97-104
Number of pages8
JournalBrain research
Volume1419
DOIs
Publication statusPublished - 2011 Oct 24

Keywords

  • CaMKII
  • HB-EGF
  • Keywords
  • LTP
  • Memory
  • Neurotrophic factor

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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