INVESTIGADORES
NAVIGATORE FONZO Lorena Silvina
artículos
Título:
INTRACEREBROVENTRICULAR INJECTION OF AMYLOID-BETA PEPTIDE (1-42) AGGREGATES MODIFIES DAILY TEMPORAL ORGANIZATION OF CLOCK FACTORS EXPRESSION, PROTEIN CARBONYLS AND ANTIOXIDANT ENZYMES IN THE RAT HIPPOCAMPUS
Autor/es:
NAVIGATORE FONZO LORENA; ALFARO MAURO; MAZAFERRO PAULA; GOLINI REBECA; LEPORATTI, JORGE; DELLA VEDOBA CECILIA; RAMIREZ DARIO; DELSOUC BELEN; CASAIS MARILINA; ANZULOVICH, ANA CECILIA
Revista:
BRAIN RESEARCH
Editorial:
ELSEVIER SCIENCE BV
Referencias:
Lugar: Amsterdam; Año: 2021
ISSN:
0006-8993
Resumen:
ABSTRACTAlzheimerdisease(AD)isthemostfrequentformofdementiaintheelderly.Itischaracterizedbythedete-riorationofmemoryandlearning.ThehistopathologicalhallmarksofADincludethepresenceofextracellu-lardepositsofamyloidbetapeptide,intracellularneurofibrillarytangles,neuronandsynapseloss,inthebrain,includingthehippocampus.AccumulationofAβpeptidecausesanincreaseinintracellularreactiveoxygenspecies(ROS)andfreeradicalsassociatedtoadeficientantioxidantdefensesystem.Besidesoxida-tivestressandcognitivedeficit,ADpatientsshowalterationsintheircircadianrhythms.TheobjectiveofthisworkwastoinvestigatetheeffectsofanintracerebroventricularinjectionofamyloidbetapeptideAβ(1?42)aggregatesontemporalpatternsofproteinoxidation,antioxidantenzymesandclockfactorsintherathippocampus.Four-month-oldmaleHoltzmanratsdividedintothegroupscontrol(CO)andAβ-injected(Aβ),weremaintainedunder12 h-light12h-darkconditionsandreceivedwaterandfoodad-libitum.Hip-pocampussampleswereisolatedevery6 hduringa24 hperiod.Ourresultsshoweddailypatternsofpro-teincarbonyls,catalase(CAT)andglutathioneperoxidase(GPx)expressionandactivity,aswellasRorαandRev-erbßmRNA,intherathippocampus.Interestingly,anintracerebroventricularinjectionofAβaggre-gatesmodifieddailyoscillationofproteincarbonylslevels,phase-shifteddailyrhythmsofclockgenesandhadadifferentialeffectonthedailyexpressionandactivityofCATandGPx.Thus,Aβaggregatesmightaf-fectclock-mediatedtranscriptionalregulationofantioxidantenzymes,byaffectingtheformationofBMAL1:CLOCKheterodimer,probably,asaconsequenceofthealterationoftheredoxstateobservedinratsinjectedwithAβ.