title: Neuroplastin 65 mediates cognitive functions via excitatory/inhibitory synapse imbalance and ERK signal pathway.
abstract: Neuroplastin 65 (NP65) is a brain-specific glycoprotein component of synaptic membrane, which is predominantly located in the forebrain such as the cortex, amygdala and striatum and hippocampus. Previous studies have shown that NP65 is implicated in synaptic plasticity, so it was hypothesized to play roles in cognitive functions. To test this hypothesis, we generated NP65 knock-out (KO) mice and found that the null mice exhibited enhanced hippocampus-dependent learning and memory as manifested by Morris water maze test and step-through passive avoidance test, but showed anxiety-like behaviors as manifested by open field test and light/dark exploration test. In addition, molecular and cellular studies revealed several alterations including: (1) the enhanced ratio of excitatory to inhibitory synapses; (2) increased expression of NMDA receptors NR2A; (3) enhanced activation of ERK signaling; (4) lowered number of the mushroom- and bifurcate-shaped dendritic spines in NP65 KO mice. Together, our findings suggest that NP65 may mediate cognitive functions.
authors.affiliation: Department of Anatomy and Neurobiology, Tongji University School of Medicine, Shanghai 200092, China.
authors.forename: Siyiti
authors.initials: S
authors.lastname: Amuti
authors.affiliation: Research Center for Sectional and Imaging Anatomy, Shandong University School of Medicine, Jinan, Shandong 250012, China.
authors.forename: Yuchun
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Anatomy and Neurobiology, Tongji University School of Medicine, Shanghai 200092, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Anatomy and Neurobiology, Tongji University School of Medicine, Shanghai 200092, China.
authors.forename: Lifen
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Anatomy and Neurobiology, Tongji University School of Medicine, Shanghai 200092, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Anatomy and Neurobiology, Tongji University School of Medicine, Shanghai 200092, China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Anatomy and Neurobiology, Tongji University School of Medicine, Shanghai 200092, China.
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Anatomy and Neurobiology, Tongji University School of Medicine, Shanghai 200092, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Jiang
authors.affiliation: Department of Neurology, Shanghai Tongji Hospital, Tongji University School of Medicine, 200065, China.
authors.forename: Geying
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Anatomy and Neurobiology, Tongji University School of Medicine, Shanghai 200092, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Neurology, Shanghai Tongji Hospital, Tongji University School of Medicine, 200065, China; Department of Anatomy and Neurobiology, Tongji University School of Medicine, Shanghai 200092, China. Electronic address: yqiongl@tongji.edu.cn.
authors.forename: Qionglan
authors.initials: Q
authors.lastname: Yuan
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics; D001362:Avoidance Learning / Q000502:physiology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003071:Cognition / Q000502:physiology*; D049229:Dendritic Spines / Q000473:pathology; D007858:Learning / Q000502:physiology*; D020935:MAP Kinase Signaling System; D018782:Maze Learning / Q000502:physiology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008568:Memory / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013569:Synapses / Q000378:metabolism / Q000502:physiology*
chemical_list: D008562:Membrane Glycoproteins; D016194:Receptors, N-Methyl-D-Aspartate; C577174:neuroplastin protein, mouse
keywords: Anxiety behaviors; Learning and memory; Neuroplastin 65; Synaptic plasticity