GABAergic Control of Critical Developmental Periods for Anxiety- and Depression-Related Behavior in Mice 英文参考文献.docVIP
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GABAergic Control of Critical Developmental Periods for Anxiety- and Depression-Related Behavior in Mice 英文参考文献
GABAergicControlofCriticalDevelopmentalPeriodsfor
Anxiety-andDepression-RelatedBehaviorinMice
QiuyingShen1,2,4,ThomasFuchs1,4,NadiaSahir1,4,BernhardLuscher1,2,3,4
*
1Department of Biology, Pennsylvania State University, University Park, Pennsylvania, United States of America, 2Department of Biochemistry Molecular Biology,
Pennsylvania StateUniversity, UniversityPark,Pennsylvania, UnitedStatesofAmerica,3DepartmentofPsychiatry,Pennsylvania StateUniversity, CollegeofMedicine,
Hershey, Pennsylvania, United States of America, 4Center for Molecular Investigation of Neurological Disorders, Pennsylvania State University, University Park,
Pennsylvania,UnitedStatesofAmerica
Abstract
Vulnerabilityforanxietyanddepressivedisordersisthoughttohaveoriginsinearlylifeandisincreasinglyrecognizedto
involvedeficitsinGABAergicneurotransmission.Micethatwererenderedheterozygousforthec2subunitgeneofGABAA
receptors(GABAARs)showbehavioral,cognitive,neuroendocrineandpharmacologicfeaturesexpectedofamousemodel
ofmelancholicanxiousdepression,includingreducedsurvivalofadult-bornhippocampalneurons.Hereweembarkedon
elucidatingthedevelopmentalsubstrateunderlyingthisphenotype,focusingontheElevatedPlusMazeandForcedSwim
Test as relevant behavioral paradigms. In a first series of experiments using hemizygous tamoxifen-induced genetic
inactivationofafloxedc2genomiclocusweshowthatreducingthegenedosageatpostnataldays(P)13/14butnotP27/28
resultsinalteredbehaviorinbothofthesetestsinadulthood,reminiscentoftheanxious-depressivephenotypepreviously
describedforglobalheterozygousmice.However,incontrasttoglobalheterozygousmice,thebehavioralchangesinduced
byc2subunitknockdownatP13/14occurredwithoutchangesinadulthippocampalneurogenesis,indicatingthataltered
neurogenesisisnotanabsoluteprerequisiteforanxiety-anddepression-relatedbehaviorinthismodel.Inaseparateseries
ofexperimentsusingapharmacologicalapproach,acutebuttransientpotentiationofGABAARswithdiazepamuncovered
distinctdevelopmentalvulnerabilitiesforalter
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