Behavioral Consequences of NMDA Antagonist-Induced Neuroapoptosis in the Infant Mouse Brain 英文参考文献.docVIP

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Behavioral Consequences of NMDA Antagonist-Induced Neuroapoptosis in the Infant Mouse Brain 英文参考文献.doc

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Behavioral Consequences of NMDA Antagonist-Induced Neuroapoptosis in the Infant Mouse Brain 英文参考文献

BehavioralConsequencesofNMDAAntagonist-Induced NeuroapoptosisintheInfantMouseBrain CarlaM.Yuede1,2*.,DavidF.Wozniak1.,CatherineE.Creeley1,GeorgeT.Taylor2,JohnW.Olney1, NuriB.Farber1. 1DepartmentofPsychiatry,WashingtonUniversitySchoolofMedicine,St.Louis,Missouri,UnitedStatesofAmerica,2DepartmentofPsychology,UniversityofMissouri, St.Louis,Missouri,UnitedStatesofAmerica Abstract Background: Exposure to NMDA glutamate antagonists during the brain growth spurt period causes widespread neuroapoptosisintherodentbrain.Thisperiodinrodentsoccursduringthefirsttwoweeksafterbirth,andcorrespondsto thethirdtrimesterofpregnancyandseveralyearsafterbirthinhumans.Thedevelopinghumanbrainmaybeexposedto NMDAantagoniststhroughdrug-abusingmothersorthroughanesthesia. Methodology/PrincipalFindings:Weevaluatedthelong-termneurobehavioraleffectsofmiceexposedtoasingledoseof theNMDAantagonist,phencyclidine(PCP),orsaline,onpostnatalday2(P2)orP7,oronbothP2andP7.PCPtreatmenton P2 + P7 caused more severe cognitive impairments than either single treatment. Histological examination of acute neuroapoptosisresultingfromexposuretoPCPindicatedthattheregionalpatternofdegenerationinducedbyPCPinP2 pupswasdifferentfromthatinP7pups.TheextentofdamagewhenevaluatedquantitativelyonP7wasgreaterforpups previouslytreatedonP2comparedtopupstreatedonlyonP7. Conclusions:ThesefindingssignifythatPCPinducesdifferentpatternsofneuroapoptosisdependingonthedevelopmental ageatthetimeofexposure,andthatexposureattwoseparatedevelopmentalagescausesmoresevereneuropathological andneurobehavioralconsequencesthanasingletreatment. Citation:YuedeCM,WozniakDF,CreeleyCE,TaylorGT,OlneyJW,etal.(2010)BehavioralConsequencesofNMDAAntagonist-InducedNeuroapoptosisinthe InfantMouseBrain.PLoSONE5(6):e11374.doi:10.1371/journal.pone.0011374 Editor:JoeZ.Tsien,MedicalCollegeofGeorgia,UnitedStatesofAmerica ReceivedMay9,2010;AcceptedMay27,2010;PublishedJune29,2010 Copyright: ? 2010 Yuede et al. This is an open-access article distributed under the terms of