Spatial and Temporal Profiles of Growth Factor Expression during CNS Demyelination Reveal the Dynamics of Repair Priming 英文参考文献.docVIP

SpatialandTemporalProfilesofGrowthFactor ExpressionduringCNSDemyelinationRevealthe DynamicsofRepairPriming ViktoriaGudi1,2,JelenaSkuljecˇ 1,2,Ozlem¨ Yildiz1,KonstantinFrichert1,ThomasSkripuletz1 ,Darius Moharregh-Khiabani1,ElkeVo?1,KirstenWissel3,SabineWolter4,MartinStangel1,2* 1DepartmentofNeurology,HannoverMedicalSchool,Hannover,Germany,2CenterforSystemsNeuroscience,Hannover,Germany,3DepartmentofOtolaryngology, HannoverMedicalSchool,Hannover,Germany,4DepartmentofPharmacology,HannoverMedicalSchool,Hannover,Germany Abstract Demyelinationisthecauseofdisabilityinvariousneurologicaldisorders.Itisthereforecrucialtounderstandthemolecular regulation of oligodendrocytes, the myelin forming cells in the CNS. Growth factors are known to be essential for the development and maintenance of oligodendrocytes and are involved in the regulation of glial responses in various pathologicalconditions.Weemployedthewellestablishedmurinecuprizonemodeloftoxicdemyelinationtoanalyzethe expressionof13growthfactorsintheCNSduringde-andremyelination.ThetemporalmRNAexpressionprofileduring demyelination and the subsequent remyelination were analyzed separately in the corpus callosum and cerebral cortex usinglasermicrodissectionandreal-timePCRtechniques.DuringdemyelinationasimilarpatternofgrowthfactormRNA expressionwasobservedinbothareaswithastrongup-regulationofNRG1andGDNFandaslightincreaseofCNTFinthe firstweekofcuprizonetreatment.HGF,FGF-2,LIF,IGF-I,andTGF-?1wereup-regulatedmainlyduringpeakdemyelination. In contrast, during remyelination there were regional differences in growth factor mRNA expression levels. GDNF, CNTF, HGF, FGF-2, and BDNF were elevated in the corpus callosum but not in the cortex, suggesting tissue differences in the molecularregulationofremyelinationinthewhiteandgreymatter.Toclarifythecellularsourceweisolatedmicrogliafrom the cuprizone lesions. GDNF, IGF-1, and FGF mRNA were detected in the microglial fraction with a temporal pattern correspondingtothatfromwho