NMDA receptor blockade ameliorates abnormalities of spike firing of subthalamic nucleus neurons in a parkinsonian nonhuman primate.
J Neurosci Res
; 96(7): 1324-1335, 2018 07.
Article
em En
| MEDLINE
| ID: mdl-29577359
ABSTRACT
N-methyl-D-aspartate receptors (NMDARs) are ion channels comprising tetrameric assemblies of GluN1 and GluN2 receptor subunits that mediate excitatory neurotransmission in the central nervous system. Of the four different GluN2 subunits, the GluN2D subunit-containing NMDARs have been suggested as a target for antiparkinsonian therapy because of their expression pattern in some of the basal ganglia nuclei that show abnormal firing patterns in the parkinsonian state, specifically the subthalamic nucleus (STN). In this study, we demonstrate that blockade of NMDARs altered spike firing in the STN in a male nonhuman primate that had been rendered parkinsonian by treatment with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. In accompanying experiments in male rodents, we found that GluN2D-NMDAR expression in the STN was reduced in acutely or chronically dopamine-depleted animals. Taken together, our data suggest that blockade of NMDARs in the STN may be a viable antiparkinsonian strategy, but that the ultimate success of this approach may be complicated by parkinsonism-associated changes in NMDAR expression in the STN.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
2-Amino-5-fosfonovalerato
/
Receptores de N-Metil-D-Aspartato
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Núcleo Subtalâmico
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Transtornos Parkinsonianos
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article