Blockade of NR2A-Containing NMDA Receptors Induces Tau Phosphorylation in Rat Hippocampal Slices
Physiological activation of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors has been proposed to play a key role in both neuronal cell function and dysfunction. In the present study, we used selective NMDA receptor antagonists to investigate the involvement of NR2A and NR2B subunits i...
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| Format: | Article |
| Language: | English |
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Wiley
2010-01-01
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| Series: | Neural Plasticity |
| Online Access: | http://dx.doi.org/10.1155/2010/340168 |
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| author | Julie Allyson Eve Dontigny Yves Auberson Michel Cyr Guy Massicotte |
| author_facet | Julie Allyson Eve Dontigny Yves Auberson Michel Cyr Guy Massicotte |
| author_sort | Julie Allyson |
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| description | Physiological activation of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors has been proposed to play a key role in both neuronal cell function and dysfunction. In the present study, we used selective NMDA receptor antagonists to investigate the involvement of NR2A and NR2B subunits in the modulatory effect of basal NMDA receptor activity on the phosphorylation of Tau proteins. We observed, in acute hippocampal slice preparations, that blockade of NR2A-containing NMDA receptors by the NR2A antagonist NVP-AAM077 provoked the hyperphosphorylation of a residue located in the proline-rich domain of Tau (i.e., Ser199). This effect seemed to be Ser199 specific as there was no increase in phosphorylation at Ser262 and Ser409 residues located in the microtubule-binding and C-terminal domains of Tau proteins, respectively. From a mechanistic perspective, our study revealed that blockade of NR2A-containing receptors influences Tau phosphorylation probably by increasing calcium influx into neurons, which seems to rely on accumulation of new NR1/NR2B receptors in neuronal membranes and could involve the cyclin-dependent kinase 5 pathway. |
| format | Article |
| id | doaj-art-3074dee4450741bca9e6d1b68f01e758 |
| institution | Kabale University |
| issn | 2090-5904 1687-5443 |
| language | English |
| publishDate | 2010-01-01 |
| publisher | Wiley |
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| series | Neural Plasticity |
| spelling | doaj-art-3074dee4450741bca9e6d1b68f01e7582025-02-03T01:09:10ZengWileyNeural Plasticity2090-59041687-54432010-01-01201010.1155/2010/340168340168Blockade of NR2A-Containing NMDA Receptors Induces Tau Phosphorylation in Rat Hippocampal SlicesJulie Allyson0Eve Dontigny1Yves Auberson2Michel Cyr3Guy Massicotte4Département de chimie-biologie, Université du Québec à Trois-Rivières, Trois-Rivières, QC, G9A 5H7, CanadaDépartement de chimie-biologie, Université du Québec à Trois-Rivières, Trois-Rivières, QC, G9A 5H7, CanadaNovartis Institutes for BioMedical Research, 4002 Basel, SwitzerlandDépartement de chimie-biologie, Université du Québec à Trois-Rivières, Trois-Rivières, QC, G9A 5H7, CanadaDépartement de chimie-biologie, Université du Québec à Trois-Rivières, Trois-Rivières, QC, G9A 5H7, CanadaPhysiological activation of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors has been proposed to play a key role in both neuronal cell function and dysfunction. In the present study, we used selective NMDA receptor antagonists to investigate the involvement of NR2A and NR2B subunits in the modulatory effect of basal NMDA receptor activity on the phosphorylation of Tau proteins. We observed, in acute hippocampal slice preparations, that blockade of NR2A-containing NMDA receptors by the NR2A antagonist NVP-AAM077 provoked the hyperphosphorylation of a residue located in the proline-rich domain of Tau (i.e., Ser199). This effect seemed to be Ser199 specific as there was no increase in phosphorylation at Ser262 and Ser409 residues located in the microtubule-binding and C-terminal domains of Tau proteins, respectively. From a mechanistic perspective, our study revealed that blockade of NR2A-containing receptors influences Tau phosphorylation probably by increasing calcium influx into neurons, which seems to rely on accumulation of new NR1/NR2B receptors in neuronal membranes and could involve the cyclin-dependent kinase 5 pathway.http://dx.doi.org/10.1155/2010/340168 |
| spellingShingle | Julie Allyson Eve Dontigny Yves Auberson Michel Cyr Guy Massicotte Blockade of NR2A-Containing NMDA Receptors Induces Tau Phosphorylation in Rat Hippocampal Slices Neural Plasticity |
| title | Blockade of NR2A-Containing NMDA Receptors Induces Tau Phosphorylation in Rat Hippocampal Slices |
| title_full | Blockade of NR2A-Containing NMDA Receptors Induces Tau Phosphorylation in Rat Hippocampal Slices |
| title_fullStr | Blockade of NR2A-Containing NMDA Receptors Induces Tau Phosphorylation in Rat Hippocampal Slices |
| title_full_unstemmed | Blockade of NR2A-Containing NMDA Receptors Induces Tau Phosphorylation in Rat Hippocampal Slices |
| title_short | Blockade of NR2A-Containing NMDA Receptors Induces Tau Phosphorylation in Rat Hippocampal Slices |
| title_sort | blockade of nr2a containing nmda receptors induces tau phosphorylation in rat hippocampal slices |
| url | http://dx.doi.org/10.1155/2010/340168 |
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