NMDA receptor GluN2D subunit participates to levodopa-induced dyskinesia pathophysiology.

NMDA receptor GluN2D subunit participates to levodopa-induced dyskinesia pathophysiology. Neurobiol Dis. 2018 Sep 24;: Authors: Mellone M, Zianni E, Stanic J, Campanelli F, Marino G, Ghiglieri V, Longhi A, Thiolat ML, Li Q, Calabresi P, Bezard E, Picconi B, Di Luca M, Gardoni F Abstract In the striatum, specific N-methyl-d-aspartate receptor (NMDAR) subtypes are found in different neuronal cells. Spiny projection neurons (SPNs) are characterized by NMDARs expressing GluN2A and GluN2B subunits, while GluN2D is exclusively detected in striatal cholinergic interneurons (ChIs). In Parkinson's disease (PD), dopamine depletion and prolonged treatment with levodopa (L-DOPA) trigger adaptive changes in the glutamatergic transmission from the cortex to the striatum, also resulting in the aberrant function of striatal NMDARs. While modifications of GluN2A- and GluN2B-NMDARs in SPNs have been extensively documented, only few studies reported GluN2D dysfunction in PD and no data are available in L-DOPA-induced dyskinesia (LID). Here we investigate the contribution of a specific NMDAR subtype (GluN2D-NMDAR) to PD and LID, and whether this receptor could represent a candidate for future pharmacological interventions. Our results show that GluN2D synaptic abundance is selectively augmented in the striatum of L-DOPA-treated male parkinsonian rats displaying a dyskinetic phenotype. This event is associated to a dramatic increase in GluN2D binding to ...
Source: Neurobiology of Disease - Category: Neurology Authors: Tags: Neurobiol Dis Source Type: research