Academic Journal
RNA-seq and network analysis reveal unique glial gene expression signatures during prion infection
| العنوان: | RNA-seq and network analysis reveal unique glial gene expression signatures during prion infection |
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| المؤلفون: | Carroll, James A., Race, Brent, Williams, Katie, Striebel, James, Chesebro, Bruce |
| المساهمون: | Division of Intramural Research, National Institute of Allergy and Infectious Diseases |
| المصدر: | Molecular Brain ; volume 13, issue 1 ; ISSN 1756-6606 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2020 |
| الوصف: | Background Prion diseases and prion-like disorders, including Alzheimer’s disease and Parkinson’s disease, are characterized by gliosis and accumulation of misfolded aggregated host proteins. Ablating microglia in prion-infected brain by treatment with the colony-stimulating factor-1 receptor (CSF-1R) inhibitor, PLX5622, increased accumulation of misfolded prion protein and decreased survival time. Methods To better understand the role of glia during neurodegeneration, we used RNA-seq technology, network analysis, and hierarchical cluster analysis to compare gene expression in brains of prion-infected versus mock-inoculated mice. Comparisons were also made between PLX5622-treated prion-infected mice and untreated prion-infected mice to assess mechanisms involved in disease acceleration in the absence of microglia. Results RNA-seq and network analysis suggested that microglia responded to prion infection through activation of integrin CD11c/18 and did not adopt the expression signature associated with other neurodegenerative disease models. Instead, microglia acquired an alternative molecular signature late in the disease process. Furthermore, astrocytes expressed a signature pattern of genes which appeared to be specific for prion diseases. Comparisons were also made with prion-infected mice treated with PLX5622 to assess the impact of microglia ablation on astrocyte gene expression during prion infection. In the presence of microglia, a unique mix of transcripts associated with A1- and A2-reactive astrocytes was increased in brains of prion-infected mice. After ablation of microglia, this reactive astrocyte expression pattern was enhanced. Thus, after prion infection, microglia appeared to decrease the overall A1/A2-astrocyte responses which might contribute to increased survival after infection. Conclusions RNA-seq analysis indicated dysregulation of over 300 biological processes within the CNS during prion disease. Distinctive microglia- and astrocyte-associated expression signatures were identified ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1186/s13041-020-00610-8 |
| DOI: | 10.1186/s13041-020-00610-8.pdf |
| DOI: | 10.1186/s13041-020-00610-8/fulltext.html |
| الاتاحة: | http://dx.doi.org/10.1186/s13041-020-00610-8 https://link.springer.com/content/pdf/10.1186/s13041-020-00610-8.pdf https://link.springer.com/article/10.1186/s13041-020-00610-8/fulltext.html |
| Rights: | http://creativecommons.org/licenses/by/4.0/ ; http://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.66E3572D |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/s13041-020-00610-8 |
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