Stem cell factor and granulocyte colony-stimulating factor reduce β-amyloid deposits in the brains of APPPS1 transgenic mice 英文参考文献.docVIP

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Stem cell factor and granulocyte colony-stimulating factor reduce β-amyloid deposits in the brains of APPPS1 transgenic mice 英文参考文献.doc

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Stem cell factor and granulocyte colony-stimulating factor reduce β-amyloid deposits in the brains of APPPS1 transgenic mice 英文参考文献

Lietal.Alzheimer’sResearchTherapy2011,3:8 /content/3/2/8 RESEARCH OpenAccess Stemcellfactorandgranulocytecolony- stimulatingfactorreduceb-amyloiddepositsin thebrainsofAPP/PS1transgenicmice BinLi1,MariaEGonzalez-Toledo1,Chun-ShuPiao1,AllenGu2,RogerEKelley1,3 andLi-RuZhao1,4* Abstract Introduction:Alzheimer’sdisease(AD)iswidelyrecognizedasaseriouspublichealthproblemandheavyfinancial burden.Currently,thereisnotreatmentthatcandelayorstoptheprogressivebraindamageinAD.Recently,we demonstratedthatstemcellfactor(SCF)incombinationwithgranulocytecolony-stimulatingfactor(G-CSF)(SCF +G-CSF)hastherapeuticeffectsonchronicstroke.ThepurposeofthepresentstudyistodeterminewhetherSCF +G-CSFcanreducetheburdenofb-amyloiddepositsinamousemodelofAD. Methods:APP/PS1transgenicmicewereusedasthemodelofAD.Totrackbonemarrow-derivedcellsinthe brain,thebonemarrowoftheAPP/PS1micewasreplacedwiththebonemarrowfrommiceexpressinggreen fluorescentprotein(GFP).Sixweeksafterbonemarrowtransplantation,micewererandomlydividedintoasaline controlgroupandaSCF+G-CSF-treatedgroup.SCFincombinationwithG-CSFwasadministeredsubcutaneously for12days.Circulatingbonemarrowstemcells(CD117+ cells)werequantified1dayafterthefinalinjection.Nine monthsaftertreatment,attheageof18months,miceweresacrificed.Brainsectionswereprocessedfor immunohistochemistrytoidentifyb-amyloiddepositsandGFPexpressingbonemarrow-derivedmicrogliainthe brain. Results:SystemicadministrationofSCF+G-CSFtoAPP/PS1transgenicmiceleadstolong-termreductionof b-amyloiddepositioninthebrain.Inaddition,wehavealsoobservedthattheSCF+G-CSFtreatmentincreases circulatingbonemarrowstemcellsandaugmentsbonemarrow-derivedmicroglialcellsinthebrainsofAPP/PS1 mice.Moreover,SCF+G-CSFtreatmentresultsinenhancementoftheco-localizationofbonemarrow-derived microgliaandb-amyloiddepositsinthebrain. Conclusions:Thesedatasuggestthatbonemarrow-derivedmicrogliaplayaroleinSCF+G-CSF-inducedlong-term effectstoreduceb-amyloiddeposits.Thisstudyprovidesinsightsintothecontributionofthe