Selective Decline of Synaptic Protein Levels in the Frontal Cortex of Female Mice Deficient in the Extracellular Metalloproteinase ADAMTS1 英文参考文献.docVIP

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Selective Decline of Synaptic Protein Levels in the Frontal Cortex of Female Mice Deficient in the Extracellular Metalloproteinase ADAMTS1 英文参考文献.doc

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Selective Decline of Synaptic Protein Levels in the Frontal Cortex of Female Mice Deficient in the Extracellular Metalloproteinase ADAMTS1 英文参考文献

SelectiveDeclineofSynapticProteinLevelsinthe FrontalCortexofFemaleMiceDeficientinthe ExtracellularMetalloproteinaseADAMTS1 MatthewD.Howell1,AntoniX.Torres-Collado2,M.LuisaIruela-Arispe2,PaulE.Gottschall1* 1UniversityofArkansasforMedicalSciences,DepartmentofPharmacologyandToxicology,LittleRock,Arkansas,UnitedStatesofAmerica,2UniversityofCalifornia,Los Angeles,DepartmentofMolecular,Cell,andDevelopmentalBiology,LosAngeles,California,UnitedStatesofAmerica Abstract Thechondroitinsulfate-bearingproteoglycans,alsoknownaslecticans,areamajorcomponentoftheextracellularmatrix (ECM) in the central nervous system and regulate neural plasticity. Growing evidence indicates that endogenous, extracellularmetalloproteinasesthatcleavelecticansmediateneuralplasticitybyalteringthestructureofECMaggregates. The bulk of this in vivo data examined the matrix metalloproteinases, but another metalloproteinase family that cleaves lecticans, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS), modulates structural plasticity in vitro,althoughfewinvivostudieshavetestedthisconcept.Thus,thepurposeofthisstudywastoexaminetheneurological phenotypeofamousedeficientinADAMTS1.Adamts1mRNAwasabsentintheADAMTS1nullmousefrontalcortex,but there was no change in the abundance or proteolytic processing of the prominent lecticans brevican and versican V2. However,therewasamarkedincreaseintheperinatallecticanneurocaninjuvenileADAMTS1nullfemalefrontalcortex. Moreprominently,thereweredeclinesinsynapticproteinlevelsintheADAMTS1nullfemale,butnotmale,frontalcortex beginning at postnatal day 28. These synaptic marker declines did not affect learning or memory in the adult female ADAMTS1nullmicewhentestedwiththeradial-armwatermaze.TheseresultsindicatethatinvivoAdamts1knockoutleads to sexual dimorphism in frontal cortex synaptic protein levels. Since changes in lectican abundance and proteolytic processingdidnotaccompanythesynapticproteindeclines,ADAMTS1mayplayanonproteolyticroleinregulatingneural