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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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5377249 | PMC |
| http://dx.doi.org/10.1038/srep44921 | DOI Listing |
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