Inhaling xenon ameliorates l-dopa-induced dyskinesia in experimental parkinsonism.
Mov Disord
; 33(10): 1632-1642, 2018 10.
Article
en En
| MEDLINE
| ID: mdl-29756234
ABSTRACT
Parkinson's disease motor symptoms are treated with levodopa, but long-term treatment leads to disabling dyskinesia. Altered synaptic transmission and maladaptive plasticity of corticostriatal glutamatergic projections play a critical role in the pathophysiology of dyskinesia. Because the noble gas xenon inhibits excitatory glutamatergic signaling, primarily through allosteric antagonism of the N-methyl-d-aspartate receptors, we aimed to test its putative antidyskinetic capabilities. We first studied the direct effect of xenon gas exposure on corticostriatal plasticity in a murine model of levodopa-induced dyskinesia We then studied the impact of xenon inhalation on behavioral dyskinetic manifestations in the gold-standard rat and primate models of PD and levodopa-induced dyskinesia. Last, we studied the effect of xenon inhalation on axial gait and posture deficits in a primate model of PD with levodopa-induced dyskinesia. This study shows that xenon gas exposure (1) normalized synaptic transmission and reversed maladaptive plasticity of corticostriatal glutamatergic projections associated with levodopa-induced dyskinesia, (2) ameliorated dyskinesia in rat and nonhuman primate models of PD and dyskinesia, and (3) improved gait performance in a nonhuman primate model of PD. These results pave the way for clinical testing of this unconventional but safe approach. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Xenón
/
Levodopa
/
Trastornos Parkinsonianos
/
Discinesia Inducida por Medicamentos
/
Antiparkinsonianos
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Mov Disord
Asunto de la revista:
NEUROLOGIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Francia