Chronic Treatment with the GLP1 Analogue Liraglutide Increases Cell Proleration and Dferentiation into Neurons in an AD Mouse Model.docVIP

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Chronic Treatment with the GLP1 Analogue Liraglutide Increases Cell Proleration and Dferentiation into Neurons in an AD Mouse Model.doc

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Chronic Treatment with the GLP1 Analogue Liraglutide Increases Cell Proleration and Dferentiation into Neurons in an AD Mouse Model

ChronicTreatmentwiththeGLP1AnalogueLiraglutide IncreasesCellProliferationandDifferentiationinto NeuronsinanADMouseModel VadivelParthsarathy,ChristianHo¨lscher* SchoolofBiomedicalSciences,UlsterUniversity,Coleraine,UnitedKingdom Abstract Neurogenesisisalifelongprocess,buttherateofcellproliferationanddifferentiationdecreaseswithage.InAlzheimer’s patients,alongwithage,thepresenceofAbinthebraininhibitsthisprocessbyreducingstemcellproliferationandcell differentiation. GLP-1 is a growth factor that has neuroprotective properties. GLP1 receptors are present on neuronal progenitorcells,andtheGLP-1analogueliraglutidehasbeenshowntoincreasecellproliferationinanAlzheimer’sdisease (AD)mousemodel.Hereweinvestigatedacuteandchroniceffectsofliraglutideonprogenitorcellproliferation,neuroblast differentiationandtheirsubsequentdifferentiationintoneuronsinwildtypeandAPP/PS-1miceatdifferentages.APP/PS1 and their littermate controls, aged 3, 6, 12, 15months were injected acutely or chronically with 25nmol/kg liraglutide. Acute treatment with liraglutide showed an increase in cell proliferation in APP/PS1 mice, but not in controls whereas chronictreatmentincreasedcellproliferationatallages(BrdUandKi67markers).Moreover,numbersofimmatureneurons (DCX)wereincreasedinbothacuteandchronictreatedanimalsatallages.Mostnewlygeneratedcellsdifferentiatedinto matureneurons(NeuNmarker).Asignificantincreasewasobservedwithchronicallytreated6,12,15monthAPP/PS1and WTgroups.Theseresultsdemonstratethatliraglutide,whichiscurrentlyonthemarketasatreatmentfortype2diabetes (VictozaTM),increasesneurogenesis,whichmayhavebeneficialeffectsinneurodegenerativedisorderslikeAD. Citation:ParthsarathyV,Ho¨lscherC(2013)ChronicTreatmentwiththeGLP1AnalogueLiraglutideIncreasesCellProliferationandDifferentiationintoNeuronsin anADMouseModel.PLoSONE8(3):e58784.doi:10.1371/journal.pone.0058784 Editor:JavierVitorica,UniversidaddeSevilla,Spain ReceivedJuly13,2012;AcceptedFebruary8,2013;PublishedMarch11,2013 Copyright: ? 2013 Parthsara