title: Protective effects of EphB2 on Aβ1-42 oligomer-induced neurotoxicity and synaptic NMDA receptor signaling in hippocampal neurons.
abstract: Alzheimer's disease (AD) is a neurodegenerative disorder characterized pathologically by the abnormal deposition of extracellular amyloid-β (Aβ) oligomers. However, the nature and precise mechanism of the toxicity of Aβ oligomers are not clearly understood. Aβ oligomers have been previously shown to cause a major loss of EphB2, a member of the EphB family of receptor tyrosine kinases. To determine the effect of EphB2 on Aβ oligomer-induced neurotoxicity and the underlying molecular mechanisms, we examined the EphB2 gene in cultured hippocampal neurons. Using a cellular model of AD, Aβ1-42 oligomers were confirmed to induce neurotoxicity in a time-dependent manner and result in a major decrease of EphB2. EphB2 overexpression could prevent the neurotoxicity of hippocampal neurons from exposure to Aβ1-42 oligomers for 1h. Further analysis revealed that EphB2 overexpression increased synaptic NR1 and NR2B expression in Aβ1-42 oligomer-treated neurons. Moreover, EphB2 overexpression prevented Aβ1-42 oligomer-induced downregulation of dephosphorylated p38 MAPK and phosphorylated CREB. Together, these results suggest that EphB2 is a factor which protects hippocampal neurons against the toxicity of Aβ1-42 oligomers, and we infer that the protection of EphB2 is achieved by increasing the synaptic NMDA receptor level and downstream p38 MAPK and CREB signaling in hippocampal neurons. This study provides new molecular insights into the neuroprotective effect of EphB2 and highlights its potential therapeutic role in the management of AD.
authors.affiliation: Department of Human Anatomy, Hebei Medical University, Shijiazhuang 050017, Hebei, PR China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Geng
authors.forename: Lin
authors.initials: L
authors.lastname: Kang
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Su
authors.forename: Jianxin
authors.initials: J
authors.lastname: Jia
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.forename: Sha
authors.initials: S
authors.lastname: Li
authors.forename: Juan
authors.initials: J
authors.lastname: Du
authors.forename: Huixian
authors.initials: H
authors.lastname: Cui
mesh_terms: D016229:Amyloid beta-Peptides / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D018613:Microscopy, Confocal; D009474:Neurons / Q000378:metabolism*; D010446:Peptide Fragments / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D036183:Receptor, EphB2 / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D016194:Receptors, N-Methyl-D-Aspartate; C075222:amyloid beta-protein (1-42); D036183:Receptor, EphB2
keywords: 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazoliumbromide; AD; Alzheimer’s disease; Amyloid-β; Aβ; CREB; DIV; DMSO; EphB2; FBS; LDH; LTP; MAPK; MTT; N-methyl-D-aspartate receptor; NMDA receptor; NMDAR; Neurotoxicity; amyloid-β; cAMP response element binding protein; days in vitro; dimethyl sulfoxide; fetal bovine serum; hAPP; human amyloid precursor protein; lactate dehydrogenase; long-term potentiation; mitogen-activated protein kinase