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NMDA Receptor Subunits (nmda + receptor_subunit)
Selected AbstractsLasting changes in NMDAR1 mRNA level in various regions of cerebral cortex in epileptogenesis of amygdaloid-kindled ratPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 5 2000Shiuichi Kikuchi MD Abstract The involvement of NMDA receptor subunit, NR1, with kindling phenomenon has been reported, but the role of NR1 in epileptogenesis is still unknown. We have examined the expression levels of NR1 mRNA in the cerebral cortices of amygdaloid-kindled rats. Northern blot analysis showed a significant increase in NR1 mRNA expression level in the ipsilateral frontal and temporal cortices at 4 weeks after the last generalized seizure. At the same time, NR1 mRNA decreased in the bilateral piriform cortices. These data suggest that NR1-mediated transmission may have an impact in the neurobiological basis of enduring epileptogenesis. [source] Presynaptic localization of an AMPA-type glutamate receptor in corticostriatal and thalamostriatal axon terminalsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2004Fumino Fujiyama Abstract The neostriatum is known to receive glutamatergic projections from the cerebral cortex and thalamic nuclei. Vesicular glutamate transporters 1 and 2 (VGluT1 and VGluT2) are located on axon terminals of corticostriatal and thalamostriatal afferents, respectively, whereas VGluT3 is found in axon terminals of cholinergic interneurons in the neostriatum. In the present study, the postsynaptic localization of ionotropic glutamate receptors was examined in rat neostriatum by the postembedding immunogold method for double labelling of VGluT and glutamate receptors. Immunoreactive gold particles for AMPA receptor subunits GluR1 and GluR2/3 were frequently found not only on postsynaptic but also on presynaptic profiles immunopositive for VGluT1 and VGluT2 in the neostriatum, and GluR4-immunoreactive particles were observed on postsynaptic and presynaptic profiles positive for VGluT1. Quantitative analysis revealed that 27,45% of GluR1-, GluR2-, GluR2/3- and GluR4-immunopositive particles found in VGluT1- or VGluT2-positive synaptic structures in the neostriatum were associated with the presynaptic profiles of VGluT-positive axons. In contrast, VGluT-positive presynaptic profiles in the neostriatum showed almost no immunoreactivity for NMDA receptor subunits NR1 or NR2A/B. Furthermore, almost no GluR2/3-immunopositive particles were observed in presynaptic profiles of VGluT3-positive (cholinergic) terminals that made asymmetric synapses in the neostriatum, or in those of VGluT1- or VGluT2-positive terminals in the neocortex. The present results indicate that AMPA receptor subunits but not NMDA receptor subunits are located on axon terminals of corticostriatal and thalamostriatal afferents, and suggest that glutamate released from these axon terminals controls the activity of the terminals through the presynaptic AMPA autoreceptors. [source] NMDA receptor subunits GluR,1, GluR,3 and GluR,1 are enriched at the mossy fibre,granule cell synapse in the adult mouse cerebellumEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2001Kazuyuki Yamada Abstract Cerebellar N -methyl- d -aspartate (NMDA) receptors are concentrated in the granular layer and are involved in motor coordination and the induction of long-term potentiation at mossy fibre,granule cell synapses. In the present study, we used immunohistochemistry to examine the distribution of NMDA receptor subunits in the adult mouse cerebellum. We found that appropriate pepsin pretreatment of sections greatly enhanced the sensitivity and specificity of immunohistochemical detection. As a result, intense immunolabelling for GluR,1 (NR2A), GluR,3 (NR2C), and GluR,1 (NR1) all appeared in synaptic glomeruli of the granular layer. Double immunofluorescence showed that these subunits were colocalized in individual synaptic glomeruli. Within the glomerulus, NMDA receptor subunits were located between centrally-located huge mossy fibre terminals and peripherally-located tiny Golgi axon terminals. By immunoelectron microscopy, all three subunits were detected at the postsynaptic junction in granule cell dendrites, forming synapses with mossy fibre terminals. Consistent with the known functional localization, GluR,1, GluR,3, and GluR,1 are, thus, anatomically concentrated at the mossy fibre,granule cell synapse. By contrast, immunohistochemical signals were very low in Purkinje cell somata and dendrites in the molecular layer. The lack of GluR,1 immunolabelling in Purkinje cells was unexpected because the cells express GluR,1 mRNA at high levels and high levels of GluR,1 protein in the molecular layer were revealed by immunoblot. As Purkinje cells are exceptionally lacking GluR, expression, the discrepant result may provide in vivo evidence suggesting the importance of accompanying GluR, subunits in synaptic localization of GluR,1. [source] Protein aggregation in postsynaptic density after transient brain ischemiaJOURNAL OF NEUROCHEMISTRY, Issue 2003M. Ber, sewicz Brief cerebral ischemia causes changes in synaptic transmission and in consequence in neuronal function manifested in delayed cell death of CA1 hippocampal region. Postsynaptic density (PSD) is composed by a network of interacting proteins, including scaffolding proteins, neurotransmitter receptors, cytoskeletal proteins and protein kinases. PSD dynamically modulates signal transduction what influence the cell fate. We investigated the composition of the PSD network and effect of ischemia on its complexity. Two experimental procedures were applied. The interaction between PSD-95 and Src, Fyn, Raf-1, paxilin or NMDA receptor subunits were explored using coimmunoprecipitation method. In addition, the effect of ischemia-reperfusion on the density of PSD were evaluated by measurement of is solubility. We find out the decrease in solubility of the PSD-95, NR2A, NR2B and Raf-1. Of interest, the latter was restricted to surviving regions of hippocampus. Acknowledgement:, Financed by PBZ-KBN-002/CD/P05/2000. [source] Transient Expression of NMDA Receptor Subunit NR2B in the Developing Rat HeartJOURNAL OF NEUROCHEMISTRY, Issue 6 2000Silke Seeber Abstract: NMDA receptors represent a subtype of the ionotropicglutamate receptor family, comprising three classes of subunits (NR1, NR2A-D,NR3), which exhibit distinct patterns of regional and developmental expressionin the CNS. Recently, some NMDA receptor subunits have also been described inadult extraneuronal tissues and keratinocytes. However, their developmentalexpression patterns are currently unknown. With use of RT-PCR and western blotanalysis, the expression of NMDA receptor subunit NR2B was investigated in thedeveloping rat heart. NR2B mRNA and protein were detected in heart tissue ofrats from embryonic day 14 until postnatal day 21 but disappeared 10 weeksafter birth. In contrast, no NMDA receptor subunit NR1,,-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor subunitGluR2, or anchoring postsynaptic density protein-95 could be detected in ratheart at any developmental stage. Confocal microscopy of cultured cardiacmyocytes (CMs) from neonatal rats revealed distinct NR2B staining mainly ofintracellular structures. However, no functional NMDA receptor could bedetected on CMs by whole-cell recordings. In conclusion, high concentrationsof NR2B protein can be detected in early rat heart development, but itsfunction still remains elusive. [source] Long-lasting effects of elevated neonatal leptin on rat hippocampal function, synaptic proteins and NMDA receptor subunitsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 4 2007Claire-Dominique Walker Abstract The high circulating levels of leptin in neonatal rodents do not seem to be regulating energy balance at this age, but rather may play an important role for brain development. We tested the hypothesis that high neonatal leptin levels modify hippocampal function and production of synaptic proteins with possible long-term consequences on long-term potentiation (LTP) in adulthood. We first showed that in postnatal day (PND) 10 neonates, acute leptin treatment functionally activated leptin receptors (ObR) in the CA1 and DG regions of the hippocampus through the induction of phosphoERK1/2, but not phosphoSTAT3 protein although both phospho-proteins were induced in the arcuate nucleus. We next examined whether chronic leptin administration (3 mg/kg BW, intraperitoneally) during the first 2 weeks of life (postnatal day, PND 2,14) produces a functional signal in the hippocampus that alters the expression of NMDA receptor subunits (NR1, NR2A, NR2B), synaptic proteins and LTP in the short and long-term. In PND 10 as in adults (PND 70) rats, chronic leptin treatment increased NR1 expression in the hippocampus while reducing NR2B protein levels. Elevated hippocampal concentrations of synapsin2A and synaptophysin were detected during leptin treatment on PND 10 suggesting increased neurotransmitter release. In adults, only SNAP-25 expression was increased after neonatal leptin treatment. LTP was reduced dramatically by leptin treatment in preweaning rats although the changes did not persist until adulthood. Elevated exposure to leptin during a critical period of neonatal hippocampal development might serve to enhance NMDA-dependent functions other than LTP and have important effects on synaptogenesis and neurotransmitter release. © 2007 Wiley-Liss, Inc. [source] | ||||||||||