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1、TISSUE-SPECIFICSTEMCELLSNitricOxideExposureDivertsNeuralStemCellFatefromNeurogenesisTowardsAstrogliogenesisaaabRUXANDRACOVACU,ALEXANDREI.DANILOV,BOSONNICHRASMUSSEN,KATARINAHALLE´N,cadcaMORTENC.MOE,ANNALOBELL,CLASB.JOHANSSON,MIKAELA.SVENSSON,TOMASOLSSON,aLOUBRUNDINabDepa
2、rtmentofClinicalNeuroscience,DivisionofNeurology,NeuroimmunologyUnit,DepartmentofMolecularcMedicineandSurgery,DivisionofUrology,DepartmentofNeurosurgery,KarolinskaInstitutet,Stockholm,dSweden;BaxterLaboratoryinGeneticPharmacology,StanfordUniversitySchoolofMedicine,Stanf
3、ord,California,USAKeyWords.Autoimmunedisease•Nitricoxide•Neuralstemcell•Neuraldifferentiation•GlialdifferentiationABSTRACTRegenerationofcellsinthecentralnervoussystemisacreasedabilitytogenerateneuronswasalsofoundtobeprocessthatmightbeaffectedduringneurologicaldiseasetra
4、nsmittedtotheprogenyofthecells.NOexposurewasandtrauma.Becausenitricoxide(NO)anditsderivativesinsteadbeneficialforastroglialdifferentiation,whichwasarepowerfulmediatorsintheinflammatorycascade,weconfirmedbyincreasedactivationoftheJanustyrosinehaveinvestigatedtheeffectsof
5、pathophysiologicalconcen-kinase/signaltransducerandactivatoroftranscriptiontrationsofNOonneurogenesis,gliogenesis,andtheexpres-transductionpathway.OurfindingsrevealanewroleforsionofproneuralgenesinprimaryadultneuralstemcellNOduringneuroinflammatoryconditions,wherebyitsc
6、ultures.AfterexposuretoNO,neurogenesiswasdownregu-proastroglialfate-determiningeffectonneuralstemcellslated,andthiscorrespondedtodecreasedexpressionofthemightdirectlyinfluencetheneuroregenerativeprocess.proneuralgeneneurogenin-2and-III-tubulin.Thede-STEMCELLS2006;24:27
7、92–2800INTRODUCTIONIthasbeendemonstratedthatstemcellsareactivatedduringNitricoxide(NO)isagaseoussecondmessengerinvolvedinneuroinflammatoryconditionsduringwhichtheymigratetoandnumerousphysiologicalprocessessuchasbloodpressureregu-differentiateatthesiteofinjury[18,19].Ine
8、xperimentallation,neurotransmission,andinflammation.StudiesinDro-autoimmuneencephalomyelitis,ananimalmodelforM
