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| Status |
Public on Jan 12, 2010 |
| Title |
The responses of astrocytes stimulated by extracellular a-synuclein |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by array
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| Summary |
Abnormal neuronal aggregation of a-synuclein is implicated in the development of Parkinson’s disease. Glial cells also show extensive a-synuclein pathology and are thought to contribute to disease progression. However, the mechanism that produces the glial a-synuclein pathology and the interaction between neurons and glia in the disease-inflicted microenvironment remain unknown. Here, we show that in neuronal cells misfolded a-synuclein proteins are selectively translocated into vesicles, leading to exocytosis of the aggregated forms. More importantly, our data demonstrate that astrocytes take up the neuron-derived a-synuclein aggregates and produce a-synuclein inclusions similar to the ones found in human brains. This uptake is paralleled by changes in the gene expression profile reflecting an inflammatory response. These results suggest that astroglial a-synuclein pathology is produced by cell-to-cell transmission of neuronal a-synuclein aggregates. This transmission step is thus an important mediator of pathogenic glial responses and could qualify as a new therapeutic target.
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| Overall design |
To determine how astrocytes respond to extracellular a-synuclein, gene expression profiles were established and analyzed for nearly 22,000 rat genes using the Illumina RatRef-12 Expression BeadChip. Total RNA was isolated from astrocytes exposed for 6h or 24h to conditioned medium from cultures of a-synuclein or lacZ expressing cells.
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| Contributor(s) |
Lee H, Cho J, Rho S, Hwang D, Lee S |
| Citation(s) |
20071342 |
| |
| Submission date |
May 28, 2008 |
| Last update date |
Jul 29, 2014 |
| Contact name |
Seung-Jae Lee |
| E-mail(s) |
sjlee@konkuk.ac.kr
|
| Organization name |
Konkuk university
|
| Lab |
Laboratory of neurological diseases
|
| Street address |
1 Hwayang-dong, Gwangjin-Gu
|
| City |
Seoul |
| ZIP/Postal code |
143701 |
| Country |
South Korea |
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| Platforms (1) |
| GPL6101 |
Illumina ratRef-12 v1.0 expression beadchip |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA106199 |
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