Nampt is required for long-term depression and the function of GluN2B subunit-containing NMDA receptors.
Nampt is required for long-term depression and the function of GluN2B subunit-containing NMDA receptors.
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DOI：
10.1016/j.brainresbull.2015.10.005
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发表时间：
2015-10
影响因子：
3.8
通讯作者：
Izumi Y
中科院分区：
文献类型：
--
作者：
Stein LR;Zorumski CF;Imai S;Izumi Y
烟酰胺腺嘌呤二核苷酸（Nicotinamide adenine dinucleotide，NAD+）是细胞代谢中许多生物学过程所必需的辅酶/辅底物。哺乳动物NAD+生物合成的主要途径中的限速步骤由烟酰胺磷酸核糖基转移酶（Nampt）介导。之前，我们发现前脑兴奋性神经元中缺乏Nampt的小鼠（CamKIIαNampt−/−小鼠）表现出多动症，学习和记忆受损，焦虑样行为减少。然而，尚不清楚这些功能效应是否伴随着突触变化。在这里，我们发现CamKIIαNampt−/−小鼠在出生后第30天在Schaffer侧支通路中的长时程抑制（LTD）诱导受损，但长时程增强（LTP）诱导正常。药理学评估表明，CamKIIαNampt−/−小鼠在NMDAR亚基表达发生变化之前，也显示出含有N-甲基-D-天冬氨酸受体（NMDAR）的突触GluN 2B（NR 2B）功能障碍。这些结果支持了一个新的，重要的作用，Nampt介导的NAD+的生物合成LTD和功能的GluN 2B含有NMDAR。
Nicotinamide adenine dinucleotide (NAD+) is an essential coenzyme/cosubstrate for many biological processes in cellular metabolism. The rate-limiting step in the major pathway of mammalian NAD+ biosynthesis is mediated by nicotinamide phosphoribosyltransferase (Nampt). Previously, we showed that mice lacking Nampt in forebrain excitatory neurons (CamKIIαNampt−/− mice) exhibited hyperactivity, impaired learning and memory, and reduced anxiety-like behaviors. However, it remained unclear if these functional effects were accompanied by synaptic changes. Here, we show that CamKIIαNampt−/− mice have impaired induction of long-term depression (LTD) in the Schaffer collateral pathway, but normal induction of long-term potentiation (LTP), at postnatal day 30. Pharmacological assessments demonstrated that CamKIIαNampt−/− mice also display dysfunction of synaptic GluN2B (NR2B)-containing N-methyl-D-aspartate receptors (NMDARs) prior to changes in NMDAR subunit expression. These results support a novel, important role for Nampt-mediated NAD+ biosynthesis in LTD and in the function of GluN2B–containing NMDARs.