Memory and synaptic plasticity are impaired by dysregulated hippocampal O-GlcNAcylation

Yong Ryoul Yang, Seungju Song, Hongik Hwang, Jung Hoon Jung, Su Jeong Kim, Sora Yoon, Jin Hoe Hur, Jae Il Park, Cheol Lee, Dougu Nam, Young Kyo Seo, Joung Hun Kim, Hyewhon Rhim, Pann Ghill Suh

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27 Scopus citations

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.

Original languageEnglish
Article number44921
JournalScientific Reports
Volume7
DOIs
StatePublished - 3 Apr 2017

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