Exposure to N-Ethyl-N-Nitrosourea in Adult Mice Alters Structural and Functional Integrity of Neurogenic Sites 英文参考文献.docVIP

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Exposure to N-Ethyl-N-Nitrosourea in Adult Mice Alters Structural and Functional Integrity of Neurogenic Sites 英文参考文献.doc

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Exposure to N-Ethyl-N-Nitrosourea in Adult Mice Alters Structural and Functional Integrity of Neurogenic Sites 英文参考文献

ExposuretoN-Ethyl-N-NitrosoureainAdultMiceAlters StructuralandFunctionalIntegrityofNeurogenicSites VivianCapilla-Gonzalez1*,SaraGil-Perotin1,2,AntonioFerragud3,LuisBonet-Ponce1,JuanJose Canales3,JoseManuelGarcia-Verdugo1,4 1LaboratoriodeNeurobiologiaComparada,InstitutoCavanillesdeBiodiversidadyBiologiaEvolutiva,UniversidaddeValencia,Valencia,Spain, 2ServiciodeMedicina Intensiva, Hospital Universitario La Fe, Valencia, Spain, 3Behavioural Neuroscience, Department of Psychology, University of Canterbury, Christchurch, New Zealand, 4LaboratoriodeMorfologiaCelular,UnidadmixtaCentrodeInvestigacionPrincipeFelipe-UVEG,CIBERNED,Valencia,Spain Abstract Background:PreviousstudieshaveshownthatprenatalexposuretothemutagenN-ethyl-N-nitrosourea(ENU),aN-nitroso compound (NOC) found in the environment, disrupts developmental neurogenesis and alters memory formation. Previously,weshowedthatpostnatalENUtreatmentinducedlastingdeficitsinproliferationofneuralprogenitorsinthe subventricularzone(SVZ),themainneurogenicregionintheadultmousebrain.Thepresentstudyisaimedtoexamine,in miceexposedtoENU,boththestructuralfeaturesofadultneurogenicsites,incorporatingthedentategyrus(DG),andthe behavioralperformanceintaskssensitivetomanipulationsofadultneurogenesis. Methodology/PrincipalFindings:2-montholdmicereceived5dosesofENUandweresacrificed45daysaftertreatment. Then, an ultrastructural analysis of the SVZ and DG was performed to determine cellular composition in these regions, confirming a significant alteration. After bromodeoxyuridine injections, an S-phase exogenous marker, the immunohis- tochemicalanalysisrevealedadeficitinproliferationandadecreasedrecruitmentofnewlygeneratedcellsinneurogenic areas of ENU-treated animals. Behavioral effects were also detected after ENU-exposure, observing impairment in odor discrimination task (habituation-dishabituation test) and a deficit in spatial memory (Barnes maze performance), two functionsprimarilyrelatedtotheSVZandtheDGregions,respectively.