Role of Gap Junction Protein Connexin43 in Astrogliosis Induced by Brain Injury 英文参考文献.docVIP

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Role of Gap Junction Protein Connexin43 in Astrogliosis Induced by Brain Injury 英文参考文献.doc

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Role of Gap Junction Protein Connexin43 in Astrogliosis Induced by Brain Injury 英文参考文献

RoleofGapJunctionProteinConnexin43inAstrogliosis InducedbyBrainInjury NicolasTheodoric,JohnF.Bechberger,ChristianC.Naus,Wun-CheySin* DepartmentofCellularandPhysiologicalSciences,LifeSciencesInstitute,TheUniversityofBritishColumbia,Vancouver,BritishColumbia,Canada Abstract Astrogliosis is a process that involves morphological and biochemical changes associated with astrocyte activation in response to cell damage in the brain. The upregulation of intermediate filament proteins including glial fibrillary acidic protein (GFAP), nestin and vimentin are often used as indicators for astrogliosis. Although connexin43 (Cx43), achannel protein widely expressed in adult astrocytes, exhibits enhanced immunoreactivity in the peri-lesion region, its role in astrogliosisisstillunclear.Here,wecorrelatedthetemporalandspatialexpressionofCx43totheactivationofastrocytes andmicrogliainresponsetoanacuteneedlestabwoundinvivo.WefoundlargenumbersofmicrogliadevoidofCx43in theneedlewoundat3dayspostinjury(dpi)whilereactiveastrocytesexpressingCx43werepresentintheperipheralzone surroundingtheinjurysite.AredistributionofCx43totheneedlesite,correspondingtotheincreasedpresenceofGFAP- positivereactiveastrocytesintheregion,wasonlyapparentfrom6dpiandsustaineduntilatleast15dpi.Interestingly,the extentofmicroglialactivationandsubsequentastrogliosisinthebrainofCx43knockoutmicewassignificantlylargerthan thoseofwildtype,suggestingthat Cx43expressionlimits thedegreeofmicrogliosis. AlthoughCx43isnotessential for astrogliosisandmicroglialactivationinducedbyaneedleinjury,ourresultsdemonstratethatCx43isausefulmarkerfor injuryinducedastrogliosisduetoitsenhancedexpressionspecificallywithinasmallregionofthelesionforanextended period.Asachannelprotein,Cx43isapotentialinvivodiagnostictoolofasymptomaticbraininjury. Citation:TheodoricN,BechbergerJF,NausCC,SinW-C(2012)RoleofGapJunctionProteinConnexin43inAstrogliosisInducedbyBrainInjury.PLoSONE7(10): e47311.doi:10.1371/journal.pone.0047311 Editor:MichelleL.Bloc