Inhaling xenon ameliorates l‐dopa‐induced dyskinesia in experimental parkinsonism

• Published in: Movement disorders Vol. 33; no. 10; pp. 1632 - 1642
• Main Authors: Baufreton, Jérôme, Milekovic, Tomislav, Li, Qin, McGuire, Steve, Moraud, Eduardo Martin, Porras, Grégory, Sun, Shiqi, Ko, Wai Kin D., Chazalon, Marine, Morin, Stéphanie, Normand, Elisabeth, Farjot, Géraldine, Milet, Aude, Pype, Jan, Pioli, Elsa, Courtine, Gregoire, Bessière, Baptiste, Bezard, Erwan
• Format: Journal Article
• Language: English
• Published: United States Wiley 01.10.2018; John Wiley and Sons Inc
• Subjects: behavior; corticostriatal plasticity; Life Sciences; Neurobiology; Neurons and Cognition; NMDA; primate; rodent; NMDA; primate; corticostriatal plasticity; behavior; rodent
• ISSN: 0885-3185; 1531-8257
• DOI: 10.1002/mds.27404

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.