Article
Alpha-synuclein expressing CG4 cell line: a possible in vitro model for multiple system atrophy
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Published: | September 11, 2012 |
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Multiple system atrophy (MSA) is a rare atypical Parkinson syndrome categorized as alpha-synucleinopathy. Common neuropathological characteristics of MSA are a profound and widespread neuronal loss in the striatum, cerebellum, brain stem, and cortex as well as myelin pallor, astrogliosis, microgliosis, and alpha-synuclein aggregation in oligodendrocytes and neurons. In oligodendrocytes of MSA patients, alpha-synuclein is observed within glial cytoplasmatic inclusions (GCIs). The origin as well as the development of these GCIs is still not well understood. To better delineate this process, we analyzed the ability of an oligodendroglial cell line (Central Glia 4; CG4) to take up extracellular alpha-synuclein. Indeed, we detected alpha-synuclein immunopositive inclusions in CG4 cells after 72 h exposure to recombinant human wild-type alpha-synuclein (20 µM). Furthermore, a human wild-type alpha-synuclein expressing CG4 cell line (CG4-WTS) was generated to assess the ability of oligodendrocytes to release alpha-synuclein. However, no alpha-synuclein was detected in supernatants of CG4-WTS cells. Previous neuropathological studies focusing on the transcriptional control of oligodendrogenesis in MSA patients and its preclinical models are rare. Thus, we analyzed the expression profiles of oligodendroglial transcription factors crucial for differentiation comparing CG4 with CG4-WTS cells. We observed that mRNA of hairy enhancer of split-5 (Hes5), an effector of Notch-signaling repressing oligodendrocytic differentiation, is significantly increased in CG4-WTS cells whereas levels of myelin regulatory factor (MRF)-mRNA, an important activator for myelin genes, was significantly reduced. This expression profile suggests that alpha-synuclein delays oligodendrocytic differentiation. Taken together, our results reveal new insights into alpha-synuclein associated pathology of oligodendrocytes in MSA.