Prenatal Stress Induces Long-Term Effects in Cell Turnover in the Hippocampus-Hypothalamus-Pituitary Axis in Adult Male Rats 英文参考文献.docVIP

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Prenatal Stress Induces Long-Term Effects in Cell Turnover in the Hippocampus-Hypothalamus-Pituitary Axis in Adult Male Rats 英文参考文献.doc

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Prenatal Stress Induces Long-Term Effects in Cell Turnover in the Hippocampus-Hypothalamus-Pituitary Axis in Adult Male Rats 英文参考文献

PrenatalStressInducesLong-TermEffectsinCell TurnoverintheHippocampus-Hypothalamus-Pituitary AxisinAdultMaleRats EvaBaquedano1,2,CristinaGarc?′a-Ca′ceres1,2,YolandaDiz-Chaves3,NataliaLagunas3,IsabelCalmarza- Font3,In?igoAzcoitia4,LuisM.Garcia-Segura3,Jesu′sArgente1,2,JulieA.Chowen1,2,LauraM.Frago1,2 * 1DepartmentofPediatrics,UniversidadAuto′nomadeMadrid-HospitalInfantilUniversitarioNin?oJesu′s,Madrid,Spain,2CIBERFisiopatolog?′adeObesidadyNutricio′n (CIBERobn),InstitutodeInvestigacio′nSanitariaPrincesa,InstitutodeSaludCarlosIII,Madrid,Spain,3LaboratoryofNeuroactiveSteroids,InstitutoCajal,ConsejoSuperior deInvestigacionesCient?′ficas(CSIC),Madrid,Spain,4DepartmentofCellularBiology,SchoolofBiology,UniversidadComplutensedeMadrid,Madrid,Spain Abstract Subchronicgestationalstressleadstopermanentmodificationsinthehippocampus-hypothalamus-pituitary-adrenalaxisof offspringprobablyduetotheincreaseincirculatingglucocorticoidsknowntoaffectprenatalprogramming.Theaimofthis studywastoinvestigatewhethercellturnoverisaffectedinthehippocampus-hypothalamus-pituitaryaxisbysubchronic prenatalstressandtheintracellularmechanismsinvolved.Restraintstresswasperformedinpregnantratsduringthelast weekofgestation(45minutes;3times/day).Onlymaleoffspringwereusedforthisstudyandweresacrificedat6monthsof age.Inprenatallystressedadultsadecreaseinmarkersofcelldeathandproliferationwasobservedinthehippocampus, hypothalamus and pituitary. This was associated with an increase in insulin-like growth factor-I mRNA levels, phosphorylation ofCREB andcalpastatin levelsandinhibitionofcalpain -2 andcaspase -8activation. Levels oftheanti- apoptotic protein Bcl-2 were increased and levels of the pro-apoptotic factor p53 were reduced. In conclusion, prenatal restraintstressinducesalong-termdecreaseincellturnoverinthehippocampus-hypothalamus-pituitaryaxisthatmightbe atleastpartlymediatedbyanautocrine-paracrineIGF-Ieffect.Thesechangescouldconditiontheresponseofthisaxisto futurephysiologicalandpathophysiologicalsi