Regional, developmental and interspecies expression of the four NMDAR2 subunits, examined using monoclonal antibodies

Laurie, David J.; Bartke, Ilse; Schoepfer, Ralf; Naujoks, Kurt; Seeburg, Peter H.

doi:10.1016/s0169-328x(97)00206-4

Cited by 214 publications

(174 citation statements)

References 55 publications

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“…For example, NR2A and NR2B are most abundant in forebrain and limbic areas, NR2C is expressed predominantly in the cerebellum, and NR2D is expressed mainly in midbrain and medullary neurons. 11,12 Here, therefore, we first review NMDA receptor expression in different regions of the pain transmission pathway, from the DRG to the anterior cingulate cortex.…”

Section: Synaptic Plasticity In the Brainmentioning

confidence: 99%

Targeting the NMDA Receptor Subunit NR2B for the Treatment of Neuropathic Pain

2009

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Summary:Neuropathic pain is generally defined as a chronic pain state resulting from peripheral or central nerve injury, or both. An effective treatment for neuropathic pain is still lacking. The NMDA receptor, one type of the ionotropic glutamate receptors, is known to be important for triggering long-lasting changes in synapses. NMDA receptor-dependent synaptic plasticity plays roles not only in physiological functions such as learning and memory, but also in unwanted pathological conditions such as chronic pain. This review addresses recent progress on NMDA receptors in neuropathic pain, with particular emphasis on the NR2B-subunitcontaining receptors. The expression and function of NMDA receptors in synaptic plasticity in the pain transmission pathway from dorsal root ganglia to the anterior cingulate cortex is reviewed, and preclinical and clinical investigations of selective NMDA receptor in neuropathic pain are discussed. The NMDA receptors, in particular NR2B-containing NMDA receptors, serve as promising targets for treatment of neuropathic pain.

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Section: Synaptic Plasticity In the Brainmentioning

confidence: 99%

Targeting the NMDA Receptor Subunit NR2B for the Treatment of Neuropathic Pain

2009

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“…(Malayev et al, 2002). NR2 subunit expression differs regionally and during development (Laurie et al, 1997;Monyer et al, 1994). Thus, pregnenolone sulfate may have different effects in different regions and at different times during development.…”

Section: Action At Ligand-gated Ion-channel Receptorsmentioning

confidence: 99%

“…Receptors containing the δ subunit are unique as they are benzodiazepine-insensitive (Shivers et al, 1989) and neurosteroid sensitive (Mihalek et al, 1999;Stell et al, 2003;Wohlfarth et al, 2002). GABA A receptors containing this subunit are highly abundant in the cerebellar granule cells, hippocampus and thalamus (Laurie et al, 1997;Laurie et al, 1992a) and cortex (Mihalek et al, 1999;Pirker et al, 2000). Ablation of the δ subunit in vivo in mice results in reduced sensitivity to neurosteroids (Mihalek et al, 1999), and results in concomitant reduced expression of α4 subunits in the hippocampus and forebrain (Korpi et al, 2002;Peng et al, 2002) and increased expression in γ2 subunits in the forebrain (Korpi et al, 2002;Peng et al, 2002) and cerebellar granule cells (Tretter et al, 2001), but only in regions that express the δ subunit.…”

Section: Gaba a Receptor Expression During Embryonic Developmentmentioning

confidence: 99%

Neurosteroid regulation of central nervous system development

Mellon

2007

Pharmacology & Therapeutics

189

117

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Neurosteroids are a relatively new class of neuroactive compounds, brought to prominence in the past two decades. Despite knowing of their presence in the nervous system of various species for over twenty years and knowing of their functions as GABA A and NMDA ligands, new and unexpected functions of these compounds are continuously being identified. Absence or reduced concentrations of neurosteroids during development and in adults may be associated with neurodevelopmental, psychiatric, or behavioral disorders. Treatment with physiologic or pharmacologic concentrations of these compounds may also promote neurogenesis, neuronal survival, myelination, increased memory, and reduced neurotoxicity. This review highlights what is currently known about the neurodevelopmental functions and mechanisms of action of four distinct neurosteroids -pregnenolone, progesterone, allopregnanolone and dehydroepiandrosterone.

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“…NMDARs are heteromers composed of two essential NR1 subunits and two or three NR2 subunits (Seeburg, 1993;Cull-Candy et al, 2001). There are four NR2 subunits (NR2A-NR2D), but the NR2A and NR2B subunits predominate in the adult rat hippocampus (Laurie et al, 1997;Wenzel et al, 1997). Because the presence of different NR2 subunits may confer distinct gating and pharmacological properties to heteromeric NMDARs (Monyer et al, 1994) and couple them to different cytoplasmic signaling cascades (Sala et al, 2000;Kohr et al, 2003), we next discerned which NMDAR subpopulations are required for the induction of LTD by LFS in slices from stressed rats.…”

Section: Ltd Observed In Slices From Stressed Rats Relies On Nr2b-conmentioning

confidence: 99%

Behavioral Stress Enhances Hippocampal CA1 Long-Term Depression through the Blockade of the Glutamate Uptake

Yang¹,

Huang²,

Hsu³

2005

J. Neurosci.

169

112

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Behavioral stress has been shown to enhance long-term depression (LTD) in the CA1 region of the hippocampus, but the underlying mechanisms remain unclear. In the present study, we found that selectively blocking NR2B-containing NMDA receptors (NMDARs) abolishes the induction of LTD by prolonged low-frequency stimulation (LFS) in slices from stressed animals. Additionally, there is no need to activate NR2A-containing or synaptic NMDARs to induce this LTD, suggesting that LTD observed in slices from stressed animals is triggered primarily by extrasynaptic NMDAR activation. In contrast, stress has no effect on LTD induced by either a brief bath application of NMDA or a combination of LFS with the glutamate-uptake inhibitor DL-threo-␤-benzyloxyaspartate (DL-TBOA). Furthermore, saturation of LFS-induced LTD in slices from stressed animals occludes the subsequent induction of LTD by LFS in the presence of DL-TBOA. We also found that stress induces a profound decrease in the glutamate uptake in the synaptosomal fraction of the hippocampal CA1 region. These effects were prevented when the animals were given a glucocorticoid receptor antagonist, 11␤,17␤-11[4-(dimethylamino)phenyl]-17-hydroxy-17-(1-(propynyl)-estra-4,9-dien-3-one, before experiencing stress. These results suggest that the blockade of glutamate uptake is a potential mechanism underlying the stress-induced enhancement of LTD and point to a novel role for glutamate-uptake machinery in the regulation of synaptic plasticity induction.

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Regional, developmental and interspecies expression of the four NMDAR2 subunits, examined using monoclonal antibodies

Cited by 214 publications

References 55 publications

Targeting the NMDA Receptor Subunit NR2B for the Treatment of Neuropathic Pain

Targeting the NMDA Receptor Subunit NR2B for the Treatment of Neuropathic Pain

Neurosteroid regulation of central nervous system development

Behavioral Stress Enhances Hippocampal CA1 Long-Term Depression through the Blockade of the Glutamate Uptake

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