Early Life Stress Enhancement of Limbic Epileptogenesis in Adult Rats Mechanistic Insights 英文参考文献.docVIP

EarlyLifeStressEnhancementofLimbicEpileptogenesis inAdultRats:MechanisticInsights GauravKumar1,NigelC.Jones1,MargaretJ.Morris2,SandraRees3,TerenceJ.O’Brien1,4,5,MichaelR. Salzberg6,7 * 1DepartmentofMedicine,RoyalMelbourneHospital,UniversityofMelbourne,Parkville,Australia,2DepartmentofPharmacology,SchoolofMedicalSciences,University of New South Wales, Sydney, Australia, 3Department of Anatomy and Cell Biology, University of Melbourne, Parkville, Australia, 4Department of Neurology, Royal MelbourneHospital,UniversityofMelbourne,Parkville,Australia,5DepartmentofSurgery,RoyalMelbourneHospital,UniversityofMelbourne,Parkville,Australia,6St. Vincent’sMentalHealthService,St.Vincent’sHospital,Fitzroy,Australia,7DepartmentofPsychiatry,St.Vincent’sHospital,UniversityofMelbourne,Fitzroy,Australia Abstract Background:Exposuretoearlypostnatalstressisknowntohastentheprogressionofkindlingepileptogenesisinadultrats. Despitethesignificanceofthisforunderstandingmesialtemporallobeepilepsy(MTLE)anditsassociatedpsychopathology, researchfindingsregardingunderlyingmechanismsaresparse.Ofseveralpossibilities,oneimportantcandidatemechanism is early life ‘programming’ of the hypothalamic-pituitary-adrenal (HPA) axis by postnatal stress. Elevated corticosterone (CORT) in turn has consequences for neurogenesis and cell death relevant to epileptogenesis. Here we tested the hypothesesthatMSwouldaugmentseizure-relatedcorticosterone(CORT)releaseandenhanceneuroplasticchangesinthe hippocampus. Methodology/PrincipalFindings:Eight-weekoldWistarrats,previouslyexposedonpostnataldays2–14toeithermaternal separation stress (MS) or control brief early handling (EH), underwent rapid amygdala kindling. We measured seizure- inducedserumCORTlevelsandpost-kindlingneurogenesis(usingBrdU).Threeweekspost-kindling,ratswereeuthanized forhistologyofthehippocampalCA3cregion(pyramidalcellcounts)anddentategyrus(DG)(tocountBrdU-labelledcells and measure mossy fibre sprouting). As in our previous studies, rats exposed to M