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

NAVIGATORE FONZO LORENA; ALFARO MAURO; MAZAFERRO PAULA; GOLINI REBECA; LEPORATTI, JORGE; DELLA VEDOBA CECILIA; RAMIREZ DARIO; DELSOUC BELEN; CASAIS MARILINA; ANZULOVICH, ANA CECILIA

BRAIN RESEARCH

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2021

0006-8993

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.