Behavioral Characterization of GCLM-Knockout Mice, a Model for Enhanced Susceptibility to Oxidative Stress英文文献资料.docVIP

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Behavioral Characterization of GCLM-Knockout Mice, a Model for Enhanced Susceptibility to Oxidative Stress英文文献资料.doc

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Behavioral Characterization of GCLM-Knockout Mice, a Model for Enhanced Susceptibility to Oxidative Stress英文文献资料

HindawiPublishingCorporation JournalofToxicology Volume2011,ArticleID157687,7pages doi:10.1155/2011/157687 ResearchArticle BehavioralCharacterizationofGCLM-KnockoutMice,aModel forEnhancedSusceptibilitytoOxidativeStress TerranceJ.Kavanagh, TobyB.Cole,1,2,3GennaroGiordano,1AilaL.Co,2,3IsaacMohar,1 1 andLucioG.Costa 1,4 1 2 3 4 DepartmentofEnvironmentalandOccupationalHealthSciences,UniversityofWashington,Seattle,WA98195,USA DivisionofMedicalGenetics,UniversityofWashington,Seattle,WA98195,USA DepartmentofGenomeSciences,UniversityofWashington,Seattle,WA98195,USA DepartmentofHumanAnatomy,PharmacologyandForensicScience,UniversityofParmaMedicalSchool,43121Parma,Italy CorrespondenceshouldbeaddressedtoLucioG.Costa,lgcosta@ Received20November2010;Accepted25February2011 AcademicEditor:M.TeresaColominaFosch Copyright?2011TobyB.Coleetal.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense, whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited. Glutathione(GSH)isamajorplayerincellulardefenseagainstoxidativestress.Deletionofthemodi?ersubunitofglutamate cysteineligase(GCLM),the?rstandtherate-limitingenzymeinthesynthesisofGSH,leadstosigni?cantlylowerGSHlevels inalltissuesincludingthebrain.GCLM-knockout(Gclm?/?)micemaythusrepresentamodelforcompromisedresponseto oxidativestressamenabletoinvitroandinvivoinvestigations.InordertodeterminewhetherthediminishedGSHcontentwould byitselfcausebehavioralalterations,aseriesofbehavioraltestswerecarriedoutcomparingyoungadultGclm?/?withwild-type mice.Testsincludedtherotarod,acousticstartlere?exandprepulseinhibitionofthestartlere?ex,open?eldbehavior,andthe platformreversalvariantoftheMorrisWaterMaze.Resultsshowednodi?erencesbetweenGclm?/?andwild-typemiceinanyof theneurobehavioraltests.However,moresubtlealterations,orchangeswhichmayappearasanimalsage,cannotbeexcluded. 1.Introduction catalyticactivityandisthesiteofGSHfeedbackinhibition. By lowerin