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| Status |
Public on Jun 30, 2023 |
| Title |
Molecular and functional features of synucleinopathy-associated astrocytes |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Astrocyte (AC) involvement is a common neuropathological feature in human synucleinopathy-associated neurodegeneration. However, our understanding of the in vivo characteristics of reactive ACs in synucleinopathy remained limited. Here we report the transcriptomic and functional features of a unique synucleinopathy-associated AC (SAA) subtype in a mouse model. SAAs share a convergent transcriptomic state across synucleinopathy-laden brain regions, and are at least partially reliant on microglia for their phenotypic maintenance in vivo. Intravital imaging revealed that an upregulation of the excitatory amino acid transporter 2 (EAAT2) in synucleinopathy-affected ACs is associated with depressed neuronal activities. This is potentially mediated via increased AC glutamate uptake, as pharmacological induction of EAAT2 reproduced the same effect. With cross-species comparative analysis, we showed that the core SAA transcriptomic features are present in human aged and synucleinopathy-affected midbrain ACs, while important distinct characteristics also exist. Collectively, our results uncovered complex reactive AC changes that likely play important adaptive roles in synucleinopathy.
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| Overall design |
Mouse brain frontal cortex and midbran two regions from Huα-Syn(A53T) and wildtype mice group(3 mice each group) were acquired to perform scRNAseq.
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| Contributor(s) |
Ko H, Li Z |
| Citation missing |
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| |
| Submission date |
Jun 06, 2022 |
| Last update date |
Jun 30, 2023 |
| Contact name |
Ho Ko |
| Organization name |
The Chinese University of Hong Kong
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| Department |
Medicine and Therapeutics
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| Lab |
Ko Lab, Division of Neurology
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| Street address |
30-32 Ngan Shing Street, Shatin
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| City |
Hong Kong |
| ZIP/Postal code |
999077 |
| Country |
China |
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| Platforms (1) |
| GPL18480 |
Illumina HiSeq 1500 (Mus musculus) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA846176 |
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