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.
Sci Rep. 2017 Apr 3;7:44921. doi: 10.1038/srep44921.
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.
O-GlcNAc 修饰的蛋白质在大脑中含量丰富，与神经元功能和神经退行性疾病有关。尽管有几项研究报道了 O-GlcNAc 修饰异常调节对大脑功能的影响，但 O-GlcNAc 修饰在突触功能中的作用仍不清楚。为了了解异常的 O-GlcNAc 修饰对大脑的影响，我们使用 Oga 小鼠，其 O-GlcNAc 修饰水平升高，发现 Oga 小鼠表现出空间学习和记忆受损。与这一结果一致，Oga 小鼠表现出海马突触可塑性缺陷。由于 AMPA 受体磷酸化的失调，Oga 杂合子导致长时程增强和长时程抑制受损。这些结果表明高 O-GlcNAc 修饰在学习和记忆中起作用。
