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. Brain Res Bull. 2015 Oct 16; Authors: Stein LR, Zorumski CF, Imai SI, Izumi Y Abstract 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. PMID: 26481044 [PubMed - as supplied by publisher]
Source: Brain Research Bulletin - Category: Neurology Authors: Tags: Brain Res Bull Source Type: research