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000140510 0247_ $$2doi$$a10.1002/glia.23544
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000140510 037__ $$aDZNE-2020-06832
000140510 041__ $$aEnglish
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000140510 1001_ $$0P:(DE-2719)2810396$$aRakers, Cordula$$b0$$eFirst author$$udzne
000140510 245__ $$aStroke target identification guided by astrocyte transcriptome analysis.
000140510 260__ $$aBognor Regis [u.a.]$$bWiley-Liss$$c2019
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000140510 520__ $$aAstrocytes 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.
000140510 536__ $$0G:(DE-HGF)POF3-342$$a342 - Disease Mechanisms and Model Systems (POF3-342)$$cPOF3-342$$fPOF III$$x0
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000140510 542__ $$2Crossref$$i2018-12-26$$uhttp://doi.wiley.com/10.1002/tdm_license_1.1
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000140510 650_7 $$2NLM Chemicals$$aConnexin 43
000140510 650_7 $$2NLM Chemicals$$aGalectin 3
000140510 650_7 $$2NLM Chemicals$$aLipocalin-2
000140510 650_7 $$2NLM Chemicals$$aLuminescent Proteins
000140510 650_7 $$2NLM Chemicals$$aNerve Tissue Proteins
000140510 650_7 $$2NLM Chemicals$$aSTAT3 Transcription Factor
000140510 650_7 $$2NLM Chemicals$$aStat3 protein, mouse
000140510 650_2 $$2MeSH$$aAnimals
000140510 650_2 $$2MeSH$$aAstrocytes: metabolism
000140510 650_2 $$2MeSH$$aComputational Biology
000140510 650_2 $$2MeSH$$aConnexin 43: genetics
000140510 650_2 $$2MeSH$$aConnexin 43: metabolism
000140510 650_2 $$2MeSH$$aDisease Models, Animal
000140510 650_2 $$2MeSH$$aFemale
000140510 650_2 $$2MeSH$$aGalectin 3: genetics
000140510 650_2 $$2MeSH$$aGalectin 3: metabolism
000140510 650_2 $$2MeSH$$aGene Expression Profiling: methods
000140510 650_2 $$2MeSH$$aGene Expression Regulation: genetics
000140510 650_2 $$2MeSH$$aImmunoprecipitation
000140510 650_2 $$2MeSH$$aInfarction, Middle Cerebral Artery: pathology
000140510 650_2 $$2MeSH$$aInfarction, Middle Cerebral Artery: physiopathology
000140510 650_2 $$2MeSH$$aLipocalin-2: genetics
000140510 650_2 $$2MeSH$$aLipocalin-2: metabolism
000140510 650_2 $$2MeSH$$aLuminescent Proteins: genetics
000140510 650_2 $$2MeSH$$aLuminescent Proteins: metabolism
000140510 650_2 $$2MeSH$$aMale
000140510 650_2 $$2MeSH$$aMice
000140510 650_2 $$2MeSH$$aMice, Inbred C57BL
000140510 650_2 $$2MeSH$$aMice, Transgenic
000140510 650_2 $$2MeSH$$aNerve Tissue Proteins: metabolism
000140510 650_2 $$2MeSH$$aRhombencephalon: pathology
000140510 650_2 $$2MeSH$$aRotarod Performance Test
000140510 650_2 $$2MeSH$$aSTAT3 Transcription Factor: genetics
000140510 650_2 $$2MeSH$$aSTAT3 Transcription Factor: metabolism
000140510 7001_ $$0P:(DE-2719)2810344$$aSchleif, Melvin$$b1$$udzne
000140510 7001_ $$0P:(DE-2719)2811722$$aBlank, Nelli$$b2$$udzne
000140510 7001_ $$0P:(DE-2719)9000859$$aMatušková, Hana$$b3$$udzne
000140510 7001_ $$0P:(DE-HGF)0$$aUlas, Thomas$$b4
000140510 7001_ $$0P:(DE-HGF)0$$aHändler, Kristian$$b5
000140510 7001_ $$aTorres, Santiago Valle$$b6
000140510 7001_ $$0P:(DE-2719)2810699$$aSchumacher, Toni$$b7$$udzne
000140510 7001_ $$0P:(DE-2719)2811148$$aTai, Khalid$$b8$$udzne
000140510 7001_ $$0P:(DE-2719)2811660$$aSchultze, Joachim L$$b9$$udzne
000140510 7001_ $$0P:(DE-2719)2810253$$aJackson, Walker S$$b10$$udzne
000140510 7001_ $$0P:(DE-2719)2810273$$aPetzold, Gabor Claus Julius Peter$$b11$$eLast author$$udzne
000140510 77318 $$2Crossref$$3journal-article$$a10.1002/glia.23544$$b : Wiley, 2018-12-26$$n4$$p619-633$$tGlia$$v67$$x0894-1491$$y2018
000140510 773__ $$0PERI:(DE-600)1474828-9$$a10.1002/glia.23544$$gVol. 67, no. 4, p. 619 - 633$$n4$$p619-633$$q67:4<619 - 633$$tGlia$$v67$$x0894-1491$$y2019
000140510 8564_ $$uhttps://pub.dzne.de/record/140510/files/DZNE-2020-06832_Restricted.pdf
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