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024 7 _ |a 10.1002/glia.23544
|2 doi
024 7 _ |a pmid:30585358
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024 7 _ |a 0894-1491
|2 ISSN
024 7 _ |a 1098-1136
|2 ISSN
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037 _ _ |a DZNE-2020-06832
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Rakers, Cordula
|0 P:(DE-2719)2810396
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|e First author
|u dzne
245 _ _ |a Stroke target identification guided by astrocyte transcriptome analysis.
260 _ _ |a Bognor Regis [u.a.]
|c 2019
|b Wiley-Liss
264 _ 1 |3 online
|2 Crossref
|b Wiley
|c 2018-12-26
264 _ 1 |3 print
|2 Crossref
|b Wiley
|c 2019-04-01
336 7 _ |a article
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336 7 _ |a Output Types/Journal article
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336 7 _ |a Journal Article
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336 7 _ |a ARTICLE
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336 7 _ |a JOURNAL_ARTICLE
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336 7 _ |a Journal Article
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520 _ _ |a 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.
536 _ _ |a 342 - Disease Mechanisms and Model Systems (POF3-342)
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536 _ _ |a 344 - Clinical and Health Care Research (POF3-344)
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542 _ _ |i 2018-12-26
|2 Crossref
|u http://doi.wiley.com/10.1002/tdm_license_1.1
542 _ _ |i 2018-12-26
|2 Crossref
|u http://onlinelibrary.wiley.com/termsAndConditions#vor
588 _ _ |a Dataset connected to CrossRef, PubMed,
650 _ 7 |a Connexin 43
|2 NLM Chemicals
650 _ 7 |a Galectin 3
|2 NLM Chemicals
650 _ 7 |a Lipocalin-2
|2 NLM Chemicals
650 _ 7 |a Luminescent Proteins
|2 NLM Chemicals
650 _ 7 |a Nerve Tissue Proteins
|2 NLM Chemicals
650 _ 7 |a STAT3 Transcription Factor
|2 NLM Chemicals
650 _ 7 |a Stat3 protein, mouse
|2 NLM Chemicals
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Astrocytes: metabolism
|2 MeSH
650 _ 2 |a Computational Biology
|2 MeSH
650 _ 2 |a Connexin 43: genetics
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650 _ 2 |a Connexin 43: metabolism
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650 _ 2 |a Disease Models, Animal
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650 _ 2 |a Female
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650 _ 2 |a Galectin 3: genetics
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650 _ 2 |a Galectin 3: metabolism
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650 _ 2 |a Gene Expression Profiling: methods
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650 _ 2 |a Gene Expression Regulation: genetics
|2 MeSH
650 _ 2 |a Immunoprecipitation
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650 _ 2 |a Infarction, Middle Cerebral Artery: pathology
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650 _ 2 |a Infarction, Middle Cerebral Artery: physiopathology
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650 _ 2 |a Lipocalin-2: genetics
|2 MeSH
650 _ 2 |a Lipocalin-2: metabolism
|2 MeSH
650 _ 2 |a Luminescent Proteins: genetics
|2 MeSH
650 _ 2 |a Luminescent Proteins: metabolism
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Mice, Inbred C57BL
|2 MeSH
650 _ 2 |a Mice, Transgenic
|2 MeSH
650 _ 2 |a Nerve Tissue Proteins: metabolism
|2 MeSH
650 _ 2 |a Rhombencephalon: pathology
|2 MeSH
650 _ 2 |a Rotarod Performance Test
|2 MeSH
650 _ 2 |a STAT3 Transcription Factor: genetics
|2 MeSH
650 _ 2 |a STAT3 Transcription Factor: metabolism
|2 MeSH
700 1 _ |a Schleif, Melvin
|0 P:(DE-2719)2810344
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700 1 _ |a Blank, Nelli
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700 1 _ |a Matušková, Hana
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700 1 _ |a Ulas, Thomas
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700 1 _ |a Händler, Kristian
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700 1 _ |a Torres, Santiago Valle
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700 1 _ |a Schumacher, Toni
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700 1 _ |a Tai, Khalid
|0 P:(DE-2719)2811148
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700 1 _ |a Schultze, Joachim L
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700 1 _ |a Jackson, Walker S
|0 P:(DE-2719)2810253
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700 1 _ |a Petzold, Gabor Claus Julius Peter
|0 P:(DE-2719)2810273
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773 1 8 |a 10.1002/glia.23544
|b : Wiley, 2018-12-26
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|t Glia
|v 67
|y 2018
|x 0894-1491
773 _ _ |a 10.1002/glia.23544
|g Vol. 67, no. 4, p. 619 - 633
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856 4 _ |u https://pub.dzne.de/record/140510/files/DZNE-2020-06832_Restricted.pdf
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913 1 _ |a DE-HGF
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914 1 _ |y 2019
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LibraryCollectionCLSMajorCLSMinorLanguageAuthor
Marc 21