Behavioral Impact of the Regulation of the Brain 2-Oxoglutarate Dehydrogenase Complex by Synthetic Phosphonate Analog of 2-Oxoglutarate Implications into the Role of the Complex in Neurodegenerative Diseases英文文献资料.docVIP

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Behavioral Impact of the Regulation of the Brain 2-Oxoglutarate Dehydrogenase Complex by Synthetic Phosphonate Analog of 2-Oxoglutarate Implications into the Role of the Complex in Neurodegenerative Diseases英文文献资料.doc

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Behavioral Impact of the Regulation of the Brain 2-Oxoglutarate Dehydrogenase Complex by Synthetic Phosphonate Analog of 2-Oxoglutarate Implications into the Role of the Complex in Neurodegenerative Diseases英文文献资料

SAGE-HindawiAccesstoResearch InternationalJournalofAlzheimer’sDisease Volume2010,ArticleID749061,8pages doi:10.4061/2010/749061 ResearchArticle BehavioralImpactoftheRegulationof theBrain2-OxoglutarateDehydrogenaseComplexby SyntheticPhosphonateAnalogof2-Oxoglutarate:Implications intotheRoleoftheComplexinNeurodegenerativeDiseases L.Tro?mova, M.Lovat, A.Groznaya, E.E?mova, T.Dunaeva, M.Maslova, 1 2 2 2 2 2 A.Graf, andV.Bunik 3 2 1 2 3 DepartmentsofBiophysics,BiologyFaculty,LomonosovMoscowStateUniversity,Moscow119992,Russia DepartmentsofPhysiology,BiologyFaculty,LomonosovMoscowStateUniversity,Moscow119992,Russia BelozerskyInstituteofPhysico-ChemicalBiology,LomonosovMoscowStateUniversity,Moscow119992,Russia CorrespondenceshouldbeaddressedtoV.Bunik,bunik@belozersky.msu.ru Received15May2010;Revised5July2010;Accepted30September2010 AcademicEditor:GemmaCasadesus Copyright?2010L.Tro?movaetal.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense, whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited. Decreasedactivityofthemitochondrial2-oxoglutaratedehydrogenasecomplex(OGDHC)inbrainaccompaniesneurodegener- ativediseases.Torevealmolecularmechanismsofthisassociation,wetreatedratswithaspeci?cinhibitorofOGDHC,succinyl phosphonate,orexposedthemtohypoxicstress.Inmalestreatedwithsuccinylphosphonateandinpregnancy-sensitizedfemales experiencingacutehypobarichypoxia,werevealedupregulationofbrainOGDHC(within24hours),withtheactivityincrease presumablyrepresentingthecompensatoryresponseofbraintotheOGDHCinhibition.Thisup-regulationofbrainOGDHCwas accompaniedbyanincreaseinexploratoryactivityandadecreaseinanxietyoftheexperimentalanimals.Remarkably,thehypoxia- inducedelevationofbrainOGDHCandmostoftheassociatedbehavioralchangeswereabrogatedbysuccinylphosphonate. Theantagonisticactionofhypoxiaandsuccinylphosphonatedemonstratespotentialtherapeuticsigni?canceoft