140510 20250417133306.0 10.1002/glia.23544 doi pmid:30585358 pmid 0894-1491 ISSN 1098-1136 ISSN altmetric:53162274 altmetric DZNE-2020-06832 English 610 Rakers, Cordula P:(DE-2719)2810396 0 First author dzne Stroke target identification guided by astrocyte transcriptome analysis. Bognor Regis [u.a.] 2019 Wiley-Liss online Crossref Wiley 2018-12-26 print Crossref Wiley 2019-04-01 article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1744889540_11896 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote Astrocytes support normal brain function, but may also contribute to neurodegeneration when they become reactive under pathological conditions such as stroke. However, the molecular underpinnings of this context-dependent interplay between beneficial and detrimental properties in reactive astrogliosis have remained incompletely understood. Therefore, using the RiboTag technique, we immunopurified translating mRNAs specifically from astrocytes 72 hr after transient middle cerebral artery occlusion in mice (tMCAO), thereby generating a stroke-specific astroglial translatome database. We found that compared to control brains, reactive astrocytes after tMCAO show an enrichment of transcripts linked to the A2 phenotype, which has been associated with neuroprotection. However, we found that astrocytes also upregulate a large number of potentially neurotoxic genes. In total, we identified the differential expression of 1,003 genes and 38 transcription factors, of which Stat3, Sp1, and Spi1 were the most prominent. To further explore the effects of Stat3-mediated pathways on stroke pathogenesis, we subjected mice with an astrocyte-specific conditional deletion of Stat3 to tMCAO, and found that these mice have reduced stroke volume and improved motor outcome 72 hr after focal ischemia. Taken together, our study extends the emerging database of novel astrocyte-specific targets for stroke therapy, and supports the role of astrocytes as critical safeguards of brain function in health and disease. 342 - Disease Mechanisms and Model Systems (POF3-342) G:(DE-HGF)POF3-342 POF3-342 POF III 0 344 - Clinical and Health Care Research (POF3-344) G:(DE-HGF)POF3-344 POF3-344 POF III 1 2018-12-26 Crossref http://doi.wiley.com/10.1002/tdm_license_1.1 2018-12-26 Crossref http://onlinelibrary.wiley.com/termsAndConditions#vor Dataset connected to CrossRef, PubMed, Connexin 43 NLM Chemicals Galectin 3 NLM Chemicals Lipocalin-2 NLM Chemicals Luminescent Proteins NLM Chemicals Nerve Tissue Proteins NLM Chemicals STAT3 Transcription Factor NLM Chemicals Stat3 protein, mouse NLM Chemicals Animals MeSH Astrocytes: metabolism MeSH Computational Biology MeSH Connexin 43: genetics MeSH Connexin 43: metabolism MeSH Disease Models, Animal MeSH Female MeSH Galectin 3: genetics MeSH Galectin 3: metabolism MeSH Gene Expression Profiling: methods MeSH Gene Expression Regulation: genetics MeSH Immunoprecipitation MeSH Infarction, Middle Cerebral Artery: pathology MeSH Infarction, Middle Cerebral Artery: physiopathology MeSH Lipocalin-2: genetics MeSH Lipocalin-2: metabolism MeSH Luminescent Proteins: genetics MeSH Luminescent Proteins: metabolism MeSH Male MeSH Mice MeSH Mice, Inbred C57BL MeSH Mice, Transgenic MeSH Nerve Tissue Proteins: metabolism MeSH Rhombencephalon: pathology MeSH Rotarod Performance Test MeSH STAT3 Transcription Factor: genetics MeSH STAT3 Transcription Factor: metabolism MeSH Schleif, Melvin P:(DE-2719)2810344 1 dzne Blank, Nelli P:(DE-2719)2811722 2 dzne Matušková, Hana P:(DE-2719)9000859 3 dzne Ulas, Thomas P:(DE-HGF)0 4 Händler, Kristian P:(DE-HGF)0 5 Torres, Santiago Valle 6 Schumacher, Toni P:(DE-2719)2810699 7 dzne Tai, Khalid P:(DE-2719)2811148 8 dzne Schultze, Joachim L P:(DE-2719)2811660 9 dzne Jackson, Walker S P:(DE-2719)2810253 10 dzne Petzold, Gabor Claus Julius Peter P:(DE-2719)2810273 11 Last author dzne 10.1002/glia.23544 : Wiley, 2018-12-26 4 619-633 journal-article Crossref Glia 67 2018 0894-1491 10.1002/glia.23544 Vol. 67, no. 4, p. 619 - 633 PERI:(DE-600)1474828-9 4 67:4<619 - 633 619-633 Glia 67 2019 0894-1491 http://pub.dzne.de/record/140510/files/DZNE-2020-06832_Restricted.pdf http://pub.dzne.de/record/140510/files/DZNE-2020-06832_Restricted.pdf?subformat=pdfa pdfa VDB oai:pub.dzne.de:140510 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 0 P:(DE-2719)2810396 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 1 P:(DE-2719)2810344 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 2 P:(DE-2719)2811722 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 3 P:(DE-2719)9000859 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 7 P:(DE-2719)2810699 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 8 P:(DE-2719)2811148 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 9 P:(DE-2719)2811660 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 10 P:(DE-2719)2810253 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 11 P:(DE-2719)2810273 DE-HGF Gesundheit Erkrankungen des Nervensystems G:(DE-HGF)POF3-340 G:(DE-HGF)POF3-342 G:(DE-HGF)POF3 G:(DE-HGF)POF3-300 G:(DE-HGF)POF Disease Mechanisms and Model Systems 0 DE-HGF Gesundheit Erkrankungen des Nervensystems G:(DE-HGF)POF3-340 G:(DE-HGF)POF3-344 G:(DE-HGF)POF3 G:(DE-HGF)POF3-300 G:(DE-HGF)POF Clinical and Health Care Research 1 2019 Nationallizenz StatID:(DE-HGF)0420 StatID 2022-11-08 ger DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2022-11-08 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2022-11-08 DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2022-11-08 DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2022-11-08 DBCoverage StatID:(DE-HGF)1050 StatID BIOSIS Previews 2022-11-08 DBCoverage StatID:(DE-HGF)1030 StatID Current Contents - 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