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Blockade of NR2A-containing NMDA Receptors Induces Tau Phosphorylation in Rat Hippocampal Slices

Allyson, Julie and Dontigny, Eve and Cyr, Michel and Massicotte, Guy and Auberson, Yves (2011) Blockade of NR2A-containing NMDA Receptors Induces Tau Phosphorylation in Rat Hippocampal Slices. Neural Plasticity. p. 340168. ISSN 0792-8483

Abstract

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). Western blot analysis indicated, however, that this effect was not reproduced on Ser262 and Ser409 residues located, respectively, in the microtubule-binding and C-terminal domains of Tau proteins. 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.

Item Type: Article
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Date Deposited: 13 Oct 2015 13:16
Last Modified: 13 Oct 2015 13:16
URI: https://oak.novartis.com/id/eprint/2251

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