期刊
NEUROPHARMACOLOGY
卷 92, 期 -, 页码 108-115出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2015.01.007
关键词
Parkinson's disease; NMDA receptor; GluN2B; GluN2D; Striatum; 6-Hydroxydopamine lesion
资金
- Swedish Research Council [2008-2636, 2011-2770]
- Loo and Hans Ostermans foundation for geriatric research
- Parkinsonfonden
- Stiftelse Lars Hiertas Minne
- Tore Nilsons Stiftelse for medicinsk forskning
- Svenska Lakaresallskapet
- Karolinska Institute
- Swedish Society for Medical Research (SSMF)
The GluN2B subunit of NMDA receptors (NMDARs) is an attractive drug target for therapeutic intervention in Parkinson's disease (PD). We have used whole-cell patch clamp recordings in brain slices to examine the contribution of GluN2B and GluN2D to functional NMDARs in the striatum of the unilateral 6-hydroxydopamine-lesioned mouse model of PD. We found that current/voltage relationships of NMDAR-mediated excitatory post synaptic currents were altered in a population of medium spiny projection neurons (MSNs) in the dopamine-depleted striatum. Using antagonists for GluN2B- and GluN2D-containing NMDARs, we found that GluN2B contributes to functional NMDARs in MSNs in the intact striatum and in the striatum of control mice. The function of GluN2B-containing NMDARs is however reduced in MSNs from the dopamine-depleted striatum. GluN2D is absent in MSNs from intact striatum and from control mice, but the contribution of this subunit to functional NMDARs is increased in the dopamine-depleted striatum. These changes in the subunit composition of NMDARs are associated with a decreased protein level of GluN2B and an increased level of GluN2D in the dopamine-depleted striatum. In cholinergic interneurons from the intact striatum and control mice, both GluN2B and GluN2D contribute to functional NMDARs. The functions of G1uN2D, and to some extent GluN2B, are reduced in the dopamine-depleted striatum. Our findings demonstrate a cell-type specific reorganization of GluN2B and GluN2D in a mouse model of PD and suggest GluN2D as a potential target for the management of the disease. (C) 2015 Elsevier Ltd. All rights reserved.
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