title: Heparin-binding EGF-like growth factor is required for synaptic plasticity and memory formation.
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 Ca²⁺/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.
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu 501-1196, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Oyagi
authors.forename: Shigeki
authors.initials: S
authors.lastname: Moriguchi
authors.forename: Atsumi
authors.initials: A
authors.lastname: Nitta
authors.forename: Kenta
authors.initials: K
authors.lastname: Murata
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Oida
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tsuruma
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Shimazawa
authors.forename: Kohji
authors.initials: K
authors.lastname: Fukunaga
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hara
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D066257:Heparin-binding EGF-like Growth Factor; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology; D036341:Intercellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D017774:Long-Term Potentiation / Q000235:genetics; D008568:Memory / Q000502:physiology*; D008569:Memory Disorders / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000235:genetics*; D009924:Organ Culture Techniques; D009435:Synaptic Transmission / Q000235:genetics*
chemical_list: C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins