Methamphetamine Preconditioning Alters Midbrain Transcriptional Responses to Methamphetamine-Induced Injury in the Rat Striatum 英文参考文献.docVIP

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Methamphetamine Preconditioning Alters Midbrain Transcriptional Responses to Methamphetamine-Induced Injury in the Rat Striatum 英文参考文献.doc

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Methamphetamine Preconditioning Alters Midbrain Transcriptional Responses to Methamphetamine-Induced Injury in the Rat Striatum 英文参考文献

MethamphetaminePreconditioningAltersMidbrain TranscriptionalResponsestoMethamphetamine- InducedInjuryintheRatStriatum JeanLudCadet1*,MichaelT.McCoy1,NingShengCai1,IrinaN.Krasnova1,BruceLadenheim1 ,Genevieve Beauvais1,NataschaWilson1,WilliamWoodIII2,KevinG.Becker2,AmberB.Hodges1,3 1Molecular Neuropsychiatry Research Branch, DHHS/NIH/NIDA Intramural Research Program, Baltimore, Maryland, United States of America, 2Gene Expression and GenomicsUnit,NIH/NIAIntramuralResearchProgram,Baltimore,Maryland,UnitedStatesofAmerica,3DepartmentofPsychology,MorganStateUniversity,Baltimore, Maryland,UnitedStatesofAmerica Abstract Methamphetamine(METH)isanillicitdrugwhichisneurotoxictothemammalianbrain.Numerousstudieshaverevealed significantdecreasesindopamineandserotoninlevelsinthebrainsofanimalsexposedtomoderate-to-largeMETHdoses given within short intervals of time. In contrast, repeated injections of small nontoxic doses of the drug followed by a challenge with toxic METH doses afford significant protection against monoamine depletion. The present study was undertakentotestthepossibilitythatrepeatedinjectionsofthedrugmightbeaccompaniedbytranscriptionalchanges involved in rendering the nigrostriatal dopaminergic system refractory to METH toxicity. Our results confirm that METH preconditioning can provide significant protection against METH-induced striatal dopamine depletion. In addition, the presenceandabsenceofMETHpreconditioningwereassociatedwithsubstantialdifferencesintheidentityofthegenes whoseexpressionwasaffectedbyatoxicMETHchallenge.QuantitativePCRconfirmedMETH-inducedchangesingenesof interestandidentifiedadditionalgenesthatweredifferentiallyimpactedbythetoxicMETHchallengeinthepresenceof METHpreconditioning.Thesegenesincludesmallheatshock27kD27protein2(HspB2),thyrotropin-releasinghormone (TRH),brainderivedneurotrophicfactor(BDNF),c-fos,andsomeencodingantioxidantproteinsincludingCuZnsuperoxide dismutase(CuZnSOD),glutathioneperoxidase(GPx)-1,andhemeoxygenase-1(Hmox-1).These