Nicotinamide Protects against Ethanol-Induced Apoptotic Neurodegeneration in the Developing Mouse Brain 英文参考文献.docVIP

o PL SMEDICINE NicotinamideProtectsagainstEthanol-Induced ApoptoticNeurodegeneration intheDevelopingMouseBrain Alessandro Ieraci, Daniel G.Herrera* DepartmentofPsychiatry,WeillMedicalCollegeofCornellUniversity,NewYork,NewYork,UnitedStatesofAmerica Funding:AIwassupportedbythe Reader’sDigestFellowship,andDGH wassupportedbygrantsfromthe NationalAllianceforResearchon SchizophreniaandDepressionand theReader’sDigestFoundation. ABSTRACT Background Exposure to alcohol during brain development may cause a neurological syndrome called fetal alcohol syndrome (FAS). Ethanol induces apoptotic neuronal death at specific developmental stages, particularly during the brain-growth spurt, which occurs from the beginningofthirdtrimesterofgestationandcontinuesforseveralyearsafterbirthinhumans, whilst occuring in the first two postnatal weeks in mice. Administration of a single dose of ethanolin7-dpostnatal(P7)micetriggersactivationofcaspase-3andwidespreadapoptotic neuronal death in the forebrain, providing a possible explanation for the microencephaly observedinhumanFAS.Thepresentstudywasaimedatdeterminingwhethernicotinamide maypreventethanol-inducedneurodegeneration. CompetingInterests:Theauthors havedeclaredthatnocompeting interestsexist. AcademicEditor:CatherineY. Spong,NationalInstituteofChild HealthandHumanDevelopment, UnitedStatesofAmerica Citation:IeraciAandHerreraDG (2006)Nicotinamideprotectsagainst ethanol-inducedapoptotic neurodegenerationinthe developingmousebrain.PLoSMed 3(4):e101. MethodsandFindings P7 mice were treated with a single dose of ethanol (5g/kg), and nicotinamide was administeredfrom0hto8hafterethanolexposure.Theeffectsofnicotinamideonethanol- induced activation of caspase-3 and release of cytochrome-c from the mitochondria were analyzedbyWesternblot(n?4–7/group).DensityofFluoro-JadeB–positivecellsandNeuN- positivecellswasdeterminedinthecingulatedcortex,CA1regionofthehippocampus, and lateral dorsal nucleus of the thalamus (n ? 5–6/group). Open field