title: Overexpression of α-synuclein in oligodendrocytes does not increase susceptibility to focal striatal excitotoxicity.
abstract: BACKGROUND
  Multiple system atrophy (MSA) is a fatal adult-onset neurodegenerative disease characterized by α-synuclein (α-syn) positive oligodendroglial cytoplasmic inclusions. The latter are associated with a neuronal multisystem neurodegeneration targeting central autonomic, olivopontocerebellar and striatonigral pathways, however the underlying mechanisms of neuronal cell death are poorly understood. Previous experiments have shown that oligodendroglial α-syn pathology increases the susceptibility to mitochondrial stress and proteasomal dysfunction leading to enhanced MSA-like neurodegeneration. Here we analyzed whether oligodendroglial α-syn overexpression in a transgenic mouse model of MSA synergistically interacts with focal neuronal excitotoxic damage generated by a striatal injection of quinolinic acid (QA) to affect the degree of striatal neuronal loss.
  
  
  RESULTS
  QA injury led to comparable striatal neuronal loss and optical density of astro- and microgliosis in the striatum of transgenic and control mice. Respectively, no differences were identified in drug-induced rotation behavior or open field behavior between the groups.
  
  
  CONCLUSIONS
  The failure of oligodendroglial α-syn pathology to exacerbate striatal neuronal loss resulting from QA excitotoxicity contrasts with enhanced striatal neurodegeneration due to oxidative or proteolytic stress, suggesting that enhanced vulnerability to excitotoxicity does not occur in oligodendroglial α-synucleinopathy like MSA.
authors.affiliation: Division of Neurobiology, Department of Neurology, Medical University of Innsbruck, Innrain 66/G2, 6020, Innsbruck, Austria. daniela.kuzdas@i-med.ac.at.
authors.forename: Daniela
authors.initials: D
authors.lastname: Kuzdas-Wood
authors.affiliation: Division of Neurobiology, Department of Neurology, Medical University of Innsbruck, Innrain 66/G2, 6020, Innsbruck, Austria. lisa.fellner@i-med.ac.at.
authors.forename: Lisa
authors.initials: L
authors.lastname: Fellner
authors.affiliation: Division of Neurobiology, Department of Neurology, Medical University of Innsbruck, Innrain 66/G2, 6020, Innsbruck, Austria. Melanie.premstaller@student.i-med.ac.at.
authors.forename: Melanie
authors.initials: M
authors.lastname: Premstaller
authors.affiliation: Department of Neurology, Parkinson Center Nijmegen (ParC), Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. Carlijn.borm@gmail.com.
authors.forename: Carlijn
authors.initials: C
authors.lastname: Borm
authors.affiliation: Department of Neurology, Parkinson Center Nijmegen (ParC), Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. b.bloem@neuro.umcn.nl.
authors.forename: Bastiaan
authors.initials: B
authors.lastname: Bloem
authors.affiliation: Department of Experimental Medical Science, BMC D11, Brain Repair and Imaging in Neural Systems (BRAINS), Lund University, Klinikgatan 32, 22184, Lund, Sweden. deniz.kirik@med.lu.se.
authors.forename: Deniz
authors.initials: D
authors.lastname: Kirik
authors.affiliation: Division of Neurobiology, Department of Neurology, Medical University of Innsbruck, Innrain 66/G2, 6020, Innsbruck, Austria. gregor.wenning@i-med.ac.at.
authors.forename: Gregor K
authors.initials: GK
authors.lastname: Wenning
authors.affiliation: Division of Neurobiology, Department of Neurology, Medical University of Innsbruck, Innrain 66/G2, 6020, Innsbruck, Austria. nadia.stefanova@i-med.ac.at.
authors.forename: Nadia
authors.initials: N
authors.lastname: Stefanova
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D005911:Gliosis / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008822:Mice, Transgenic; D019578:Multiple System Atrophy / Q000473:pathology / Q000503:physiopathology*; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D009836:Oligodendroglia / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D017378:Quinolinic Acid / Q000633:toxicity*; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism*
chemical_list: C497604:SNCA protein, human; D051844:alpha-Synuclein; D017378:Quinolinic Acid