Inhaling xenon ameliorates l-dopa-induced dyskinesia in experimental parkinsonism.
Mov Disord.. 2018-05-14; :
DOI: 10.1002/mds.27404
Lire sur PubMed
Inhaling xenon ameliorates l-dopa-induced dyskinesia in experimental
parkinsonism.
Baufreton J(1)(2), Milekovic T(3), Li Q(4), McGuire S(4), Moraud EM(3), Porras
G(4), Sun S(3), Ko WKD(4), Chazalon M(1)(2), Morin S(1)(2), Normand E(5)(6),
Farjot G(7), Milet A(7), Pype J(7), Pioli E(4), Courtine G(3), Bessière B(7),
Bezard E(1)(2)(4).
Author information:
(1)Université de Bordeaux, Institut des Maladies Neurodégénératives, Bordeaux,
France.
(2)Centre National de la Recherche Scientifique Unité Mixte de Recherche 5293,
Institut des Maladies Neurodégénératives, Bordeaux, France.
(3)Center for Neuroprosthetics and Brain Mind Institute, School of Life Sciences,
Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
(4)Motac Neuroscience, UK-M15 6WE, Manchester, United Kingdom.
(5)Université de Bordeaux, Institut Interdisciplinaires des Neurosciences,
Bordeaux, France.
(6)Centre National de la Recherche Scientifique Unité Mixte de Recherche 5297,
Institut Interdisciplinaires des Neurosciences, Bordeaux, France.
(7)Air Liquide Healthcare, Paris-Saclay research center, Jouy-en-Josas, France.
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.
© 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on
behalf of International Parkinson and Movement Disorder Society.
DOI: 10.1002/mds.27404
PMID: 29756234