Overexpression of α-synuclein in oligodendrocytes does not increase susceptibility to focal striatal excitotoxicity

BMC Neuroscience

Research Article

Deniz Kirik¹  Carlijn Borm²  Bastiaan Bloem²  Melanie Premstaller³  Daniela Kuzdas-Wood³  Lisa Fellner³  Nadia Stefanova³  Gregor K. Wenning³ 

[1] Department of Experimental Medical Science, BMC D11, Brain Repair and Imaging in Neural Systems (BRAINS), Lund University, Klinikgatan 32, 22184, Lund, Sweden;Department of Neurology, Parkinson Center Nijmegen (ParC), Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands;Division of Neurobiology, Department of Neurology, Medical University of Innsbruck, Innrain 66/G2, 6020, Innsbruck, Austria;

关键词: Excitotoxicity;    Alpha-synuclein;    Quinolinic acid;    Neurodegeneration;    Striatum;    Multiple system atrophy;   

DOI  :  10.1186/s12868-015-0227-6

 received in 2015-08-26, accepted in 2015-11-25,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundMultiple 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.ResultsQA 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.ConclusionsThe 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.

【 授权许可】

CC BY   
© Kuzdas-Wood et al. 2015