title: Wnt-5a prevents Aβ-induced deficits in long-term potentiation and spatial memory in rats.
abstract: Although the neurotoxicity of amyloid β (Aβ) protein in Alzheimer's disease (AD) has been reported widely, the exact molecular mechanism underlying the Aβ-induced synaptic dysfunction and memory impairment remains largely unclear. Growing evidence indicates that wingless-type (Wnt) signaling plays an important role in neuronal development, synapse formation and synaptic plasticity. In the present study, we investigated the neuroprotective action of Wnt-5a against the synaptic damage and memory deficit induced by Aβ25-35 by using in vivo electrophysiological recording and Morris water maze (MWM) test. We found that intracerebroventricular (i.c.v.) injection of Aβ25-35 alone did not affect the baseline field excitatory postsynaptic potentials (fEPSPs) and the paired-pulse facilitation (PPF) in the hippocampal CA1 region of rats, but significantly suppressed high frequency stimulation (HFS) induced long-term potentiation (LTP); pretreatment with Wnt-5a prevented the Aβ25-35-induced suppression of hippocampal LTP in a dose-dependent manner; soluble Frizzled-related protein (sFRP), a specific Wnt antagonist, effectively attenuated the protective effects of Wnt-5a. In MWM test, Aβ25-35 alone significantly disrupted spatial learning and memory ability of rats, while pretreatment with Wnt-5a effectively prevented the impairments induced by Aβ25-35. These results in the present study demonstrated for the first time the neuroprotective effects of Wnt-5a against Aβ-induced in vivo synaptic plasticity impairment and memory disorder, suggesting that Wnt signaling pathway is one of the important targets of Aβ neurotoxicity and Wnt-5a might be used as one of the putative candidates for the therapeutic intervention of AD.
authors.affiliation: Department of Neurology, Xuanwu Hospital of Capital Medical University, 45 Changchun Street, Beijing 100053, China.
authors.forename: Gui-Li
authors.initials: GL
authors.lastname: Zhang
authors.affiliation: Department of Physiology and National Key Discipline of Physiology, Shanxi Medical University, 56 Xinjian South Road, Taiyuan, Shanxi 030001, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Physiology and National Key Discipline of Physiology, Shanxi Medical University, 56 Xinjian South Road, Taiyuan, Shanxi 030001, China.
authors.forename: Shao-Feng
authors.initials: SF
authors.lastname: Li
authors.affiliation: Department of Ultrasonography, Tianjin 4th Centre Hospital, Tianjin 300140, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Lei
authors.affiliation: Department of Neurology, First Affiliated Hospital, Jilin University, 71 Xinmin Street, Changchun, Jilin 130021, China.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Xie
authors.affiliation: Department of Neurology, First Affiliated Hospital, Jilin University, 71 Xinmin Street, Changchun, Jilin 130021, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Deng
authors.affiliation: Department of Neurology, First Affiliated Hospital, Jilin University, 71 Xinmin Street, Changchun, Jilin 130021, China. Electronic address: fengjcgood@163.com.
authors.forename: Jia-Chun
authors.initials: JC
authors.lastname: Feng
authors.affiliation: Department of Physiology and National Key Discipline of Physiology, Shanxi Medical University, 56 Xinjian South Road, Taiyuan, Shanxi 030001, China. Electronic address: jinshunqi2009@163.com.
authors.forename: Jin-Shun
authors.initials: JS
authors.lastname: Qi
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004924:Escape Reaction / Q000187:drug effects; D006023:Glycoproteins / Q000627:therapeutic use; D006624:Hippocampus / Q000187:drug effects; D047908:Intracellular Signaling Peptides and Proteins; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced* / Q000188:drug therapy*; D010446:Peptide Fragments / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D065852:Spatial Memory / Q000187:drug effects*; D051153:Wnt Proteins / Q000627:therapeutic use*; D000071818:Wnt-5a Protein; D000099274:Frizzled-Related Proteins
chemical_list: D016229:Amyloid beta-Peptides; D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D000099274:Frizzled-Related Proteins; C491837:Wnt5a protein, rat; C074636:amyloid beta-protein (25-35)
keywords: Amyloid β protein; In vivo long-term potentiation; Spatial memory; Synaptic plasticity; Wnt-5a