title: Memory and synaptic plasticity are impaired by dysregulated hippocampal O-GlcNAcylation.
abstract: O-GlcNAcylated proteins are abundant in the brain and are associated with neuronal functions and neurodegenerative diseases. Although several studies have reported the effects of aberrant regulation of O-GlcNAcylation on brain function, the roles of O-GlcNAcylation in synaptic function remain unclear. To understand the effect of aberrant O-GlcNAcylation on the brain, we used Oga+/-mice which have an increased level of O-GlcNAcylation, and found that Oga+/-mice exhibited impaired spatial learning and memory. Consistent with this result, Oga+/-mice showed a defect in hippocampal synaptic plasticity. Oga heterozygosity causes impairment of both long-term potentiation and long-term depression due to dysregulation of AMPA receptor phosphorylation. These results demonstrate a role for hyper-O-GlcNAcylation in learning and memory.
authors.affiliation: School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea.|Aging Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea.
authors.forename: Yong Ryoul
authors.initials: YR
authors.lastname: Yang
authors.affiliation: Center for Neuroscience, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 136-791, South Korea.|Department of Neuroscience, University of Science and Technology (UST), Daejeon 305-333, South Korea.
authors.forename: Seungju
authors.initials: S
authors.lastname: Song
authors.affiliation: Center for Neuroscience, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 136-791, South Korea.
authors.forename: Hongik
authors.initials: H
authors.lastname: Hwang
authors.affiliation: Department of Life Science, Pohang University of Science and Technology, Pohang, Gyungbuk 790-784, Republic of Korea.
authors.forename: Jung Hoon
authors.initials: JH
authors.lastname: Jung
authors.affiliation: Department of Life Science, Pohang University of Science and Technology, Pohang, Gyungbuk 790-784, Republic of Korea.
authors.forename: Su-Jeong
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea.
authors.forename: Sora
authors.initials: S
authors.lastname: Yoon
authors.affiliation: School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea.
authors.forename: Jin-Hoe
authors.initials: JH
authors.lastname: Hur
authors.affiliation: Korea Basic Science Institute, Gwangju 61186, Republic of Korea.
authors.forename: Jae-Il
authors.initials: JI
authors.lastname: Park
authors.affiliation: School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea.
authors.forename: Cheol
authors.initials: C
authors.lastname: Lee
authors.affiliation: School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea.
authors.forename: Dougu
authors.initials: D
authors.lastname: Nam
authors.affiliation: School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea.
authors.forename: Young-Kyo
authors.initials: YK
authors.lastname: Seo
authors.affiliation: Department of Life Science, Pohang University of Science and Technology, Pohang, Gyungbuk 790-784, Republic of Korea.
authors.forename: Joung-Hun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Center for Neuroscience, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 136-791, South Korea.|Department of Neuroscience, University of Science and Technology (UST), Daejeon 305-333, South Korea.
authors.forename: Hyewhon
authors.initials: H
authors.lastname: Rhim
authors.affiliation: School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea.
authors.forename: Pann-Ghill
authors.initials: PG
authors.lastname: Suh
mesh_terms: D000818:Animals; D049229:Dendritic Spines / Q000378:metabolism; D059330:GABAergic Neurons / Q000378:metabolism; D006031:Glycosylation; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D008568:Memory; D051379:Mice; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism; D009473:Neuronal Plasticity; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D065853:Spatial Learning; D065852:Spatial Memory; D009435:Synaptic Transmission; D001619:beta-N-Acetylhexosaminidases / Q000235:genetics / Q000378:metabolism
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D017351:N-Acetylglucosaminyltransferases; C449880:O-GlcNAc transferase; C110628:hexosaminidase C; D001619:beta-N-Acetylhexosaminidases