Differential roles of NR2A and NR2B subtypes in NMDA receptor-dependent protein synthesis in dendrites

Dat, Tran Do; Gong, Ruomu; Tang, Shao-Jun

doi:10.1016/j.neuropharm.2007.05.005

Cited by 19 publications

(12 citation statements)

References 29 publications

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“…There is also evidence that decreased NR2A subunit expression could affect synaptic plasticity (54). While it is well known that NMDARs play an essential role in dendritic protein synthesis, a process critical for synaptic plasticity, the use of highly specific NR2A and NR2B antagonists suggested in one study that NR2A activity was indispensable (85). Finally, on the electrophysiological level, where long-term potentiation and long-term depression reflect plasticity, the relative roles each subunit plays are still being elucidated.…”

Section: Discussionmentioning

confidence: 99%

Intrauterine growth restriction due to uteroplacental insufficiency decreased white matter and altered NMDAR subunit composition in juvenile rat hippocampi

Schober¹,

McKnight²,

Yu³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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Uteroplacental insufficiency (UPI), the major cause of intrauterine growth restriction (IUGR) in developed nations, predisposes to learning impairment. The underlying mechanism is unknown. Neuronal N-methyl-d-aspartate receptors (NMDARs) are critical for synaptogenesis and learning throughout life. We hypothesized that UPI-induced IUGR alters rat hippocampal NMDAR NR2A/NR2B subunit ratio and/or NR1 mRNA isoform expression and synaptic density at day 21 (P21). To test this hypothesis, IUGR was induced by bilateral uterine artery ligation of the late-gestation Sprague-Dawley dam. At P21, hippocampal NMDAR subunit mRNA and protein were measured, as were levels of synaptophysin. Neuronal, synaptic, and glial density in CA1, CA3, and dentate gyrus (DG) was assessed by immunofluorescence. IUGR increased NR1 mRNA isoform NR1-3a and 1-3b expression in both sexes. In P21 males, IUGR increased protein levels of NR1 C2' and decreased NR1 C2, NR2A, and the NR2A-to-NR2B ratio, whereas in females, IUGR increased NR2B protein. In males, IUGR was associated with decreased myelin basic protein-to-neuronal nuclei ratio in CA1, CA3, and DG. We conclude that IUGR has sex-specific effects and that neither neuronal loss nor decreased synaptic density appears to account for the changes in NMDAR subunits. Rather, it is possible that synaptic NMDAR subunit composition is altered. Our results suggest that apparent recovery in the IUGR hippocampus may be associated with synaptic hyperexcitability. We speculate that the NMDAR plays an important role in IUGR-associated cognitive impairment.

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Section: Discussionmentioning

confidence: 99%

Intrauterine growth restriction due to uteroplacental insufficiency decreased white matter and altered NMDAR subunit composition in juvenile rat hippocampi

Schober¹,

McKnight²,

Yu³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Other studies have demonstrated that protein synthesis in dendrites is critical for long-term potentiation (LTP) and long-term depression (LTD) (Kang and Schuman, 1996;Huber et al, 2000;Tang and Schuman, 2002;Bradshaw et al, 2003;Cracco et al, 2005;Mameli et al, 2007). The induction of protein synthesis is, not unexpectedly, dependent upon NMDA receptor activation (Scheetz et al, 2000;Huang et al, 2002b;Gong et al, 2006;Tran et al, 2007).…”

Section: Translational Control Of Glutamate Receptorsmentioning

confidence: 99%

Glutamate Receptor Ion Channels: Structure, Regulation, and Function

et al. 2010

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“…NMDA receptor activation also has been shown to elevate ERK1/2 signaling and increase eIF4E phosphorylation in the hippocampus, perhaps through activating the mTOR pathway. Interestingly, one report indicates that GluN2A-containing NMDA receptors mediate dendritic protein synthesis, whereas GluN2B-containing receptors do not (Tran et al, 2007), and the GluN2A and GluN2B subunits have shown to differentially regulate the mTOR and ERK signaling pathways (Kim et al, 2005, Wang et al, 2011). Thus, it is possible that NMDA receptor subunit expression might, in part, determine the signaling mechanism regulating dendritic protein synthesis.…”

Section: Translational Regulation In Dendrites and At Synapsesmentioning

confidence: 99%

Dendritic protein synthesis in the normal and diseased brain

Swanger

Bassell

2013

Neuroscience

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Synaptic activity is a spatially-limited process that requires a precise, yet dynamic, complement of proteins within the synaptic micro-domain. The maintenance and regulation of these synaptic proteins is regulated, in part, by local mRNA translation in dendrites. Protein synthesis within the postsynaptic compartment allows neurons tight spatial and temporal control of synaptic protein expression, which is critical for proper functioning of synapses and neural circuits. In this review, we discuss the identity of proteins synthesized within dendrites, the receptor-mediated mechanisms regulating their synthesis, and the possible roles for these locally synthesized proteins. We also explore how our current understanding of dendritic protein synthesis in the hippocampus can be applied to new brain regions and to understanding the pathological mechanisms underlying varied neurological diseases.

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Differential roles of NR2A and NR2B subtypes in NMDA receptor-dependent protein synthesis in dendrites

Cited by 19 publications

References 29 publications

Intrauterine growth restriction due to uteroplacental insufficiency decreased white matter and altered NMDAR subunit composition in juvenile rat hippocampi

Intrauterine growth restriction due to uteroplacental insufficiency decreased white matter and altered NMDAR subunit composition in juvenile rat hippocampi

Glutamate Receptor Ion Channels: Structure, Regulation, and Function

Dendritic protein synthesis in the normal and diseased brain

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