title: Overexpression of EphB2 in hippocampus rescues impaired NMDA receptors trafficking and cognitive dysfunction in Alzheimer model.
abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disease, which affects more and more people. But there is still no effective treatment for preventing or reversing the progression of the disease. Soluble amyloid-beta (Aβ) oligomers, also known as Aβ-derived diffusible ligands (ADDLs) play an important role in AD. Synaptic activity and cognition critically depend on the function of glutamate receptors. Targeting N-methyl-D-aspartic acid (NMDA) receptors trafficking and its regulation is a new strategy for AD early treatment. EphB2 is a key regulator of synaptic localization of NMDA receptors. Aβ oligomers could bind to the fibronectin repeats domain of EphB2 and trigger EphB2 degradation in the proteasome. Here we identified that overexpression of EphB2 with lentiviral vectors in dorsal hippocampus improved impaired memory deficits and anxiety or depression-like behaviors in APPswe/PS1-dE9 (APP/PS1) transgenic mice. Phosphorylation and surface expression of GluN2B-containing NMDA receptors were also improved. Overexpression of EphB2 also rescued the ADDLs-induced depletion of the expression of EphB2 and GluN2B-containing NMDA receptors trafficking in cultured hippocampal neurons. These results suggest that improving the decreased expression of EphB2 and subsequent GluN2B-containing NMDA receptors trafficking in hippocampus may be a promising strategy for AD treatment.
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.|Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.|Department of Anesthesiology, Xuzhou TCM Hospital, Xuzhou, Jiangsu 221009, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Hu
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.|Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Wei
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.|Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Jin
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.|Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Zheng
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.|Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.
authors.forename: Wen-Yu
authors.initials: WY
authors.lastname: Chen
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.|Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.
authors.forename: Xiao-Ya
authors.initials: XY
authors.lastname: Liu
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.|Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Shi
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.|Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.
authors.forename: Jing-Ru
authors.initials: JR
authors.lastname: Hao
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.|Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Sun
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.|Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.
authors.forename: Can
authors.identifier: 0000-0001-5552-9639
authors.initials: C
authors.lastname: Gao
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D051381:Rats; D017207:Rats, Sprague-Dawley; D036183:Receptor, EphB2 / Q000096:biosynthesis* / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D016229:Amyloid beta-Peptides; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; C586311:Ephb2 protein, mouse; D036183:Receptor, EphB2