title: The noble gas xenon provides protection and trophic stimulation to midbrain dopamine neurons.
abstract: Despite its low chemical reactivity, the noble gas xenon possesses a remarkable spectrum of biological effects. In particular, xenon is a strong neuroprotectant in preclinical models of hypoxic-ischemic brain injury. In this study, we wished to determine whether xenon retained its neuroprotective potential in experimental settings that model the progressive loss of midbrain dopamine (DA) neurons in Parkinson's disease. Using rat midbrain cultures, we established that xenon was partially protective for DA neurons through either direct or indirect effects on these neurons. So, when DA neurons were exposed to l-trans-pyrrolidine-2,4-dicarboxylic acid so as to increase ambient glutamate levels and generate slow and sustained excitotoxicity, the effect of xenon on DA neurons was direct. The vitamin E analog Trolox also partially rescued DA neurons in this setting and enhanced neuroprotection by xenon. However, in the situation where DA cell death was spontaneous, the protection of DA neurons by xenon appeared indirect as it occurred through the repression of a mechanism mediated by proliferating glial cells, presumably astrocytes and their precursor cells. Xenon also exerted trophic effects for DA neurons in this paradigm. The effects of xenon were mimicked and improved by the N-methyl-d-aspartate glutamate receptor antagonist memantine and xenon itself appeared to work by antagonizing N-methyl-d-aspartate receptors. Note that another noble gas argon could not reproduce xenon effects. Overall, present data indicate that xenon can provide protection and trophic support to DA neurons that are vulnerable in Parkinson's disease. This suggests that xenon might have some therapeutic value for this disorder.
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Inserm, CNRS, Institut du Cerveau et de la Moelle épinière (ICM), Hôpital Pitié-Salpêtrière, Paris, France.
authors.forename: Jérémie
authors.initials: J
authors.lastname: Lavaur
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Inserm, CNRS, Institut du Cerveau et de la Moelle épinière (ICM), Hôpital Pitié-Salpêtrière, Paris, France.
authors.forename: Déborah
authors.initials: D
authors.lastname: Le Nogue
authors.affiliation: Air Liquide Santé International, Medical R&D Paris, Saclay Research Center, Jouy-en Josas, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Lemaire
authors.affiliation: Air Liquide Santé International, Medical R&D Paris, Saclay Research Center, Jouy-en Josas, France.
authors.forename: Jan
authors.initials: J
authors.lastname: Pype
authors.affiliation: Air Liquide Santé International, Medical R&D Paris, Saclay Research Center, Jouy-en Josas, France.
authors.forename: Géraldine
authors.initials: G
authors.lastname: Farjot
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Inserm, CNRS, Institut du Cerveau et de la Moelle épinière (ICM), Hôpital Pitié-Salpêtrière, Paris, France.
authors.forename: Etienne C
authors.initials: EC
authors.lastname: Hirsch
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Inserm, CNRS, Institut du Cerveau et de la Moelle épinière (ICM), Hôpital Pitié-Salpêtrière, Paris, France.
authors.forename: Patrick P
authors.identifier: 0000-0001-5607-3119
authors.initials: PP
authors.lastname: Michel
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology; D003998:Dicarboxylic Acids / Q000037:antagonists & inhibitors / Q000633:toxicity; D059290:Dopaminergic Neurons / Q000187:drug effects*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008559:Memantine / Q000494:pharmacology; D008636:Mesencephalon / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009924:Organ Culture Techniques; D011759:Pyrrolidines / Q000037:antagonists & inhibitors / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D014978:Xenon / Q000494:pharmacology*
chemical_list: D018685:Anesthetics, Inhalation; D000975:Antioxidants; D002839:Chromans; D003998:Dicarboxylic Acids; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D011759:Pyrrolidines; D014978:Xenon; C083486:pyrrolidine-2,4-dicarboxylic acid; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D008559:Memantine
keywords: 
  NMDA
  ; astroglial cells; dopamine neurons; glutamate; neurodegeneration; xenon