Abstracts S337 ing,particularly;ithasbeenshownthatamyloidcancause
reduction of glutamatergic transmission and inhibition of synaptic plasticity via increased endocytosis of NMDA re-ceptors. Trace Amines (TAs) are a family of endogenous compoundswithstrongstructuralsimilaritytotheclassical monoamine neurotransmitters. The molecular mechanism of the TAs involves binding to a novel G protein-coupled receptor, called TAAR (trace amine-associated receptor). TAAR1isdistributedintheCNS.Recently,ithasbeenshown thatselectiveactivationofTAAR1areabletoreverse gluta-matergichypofunctioninducedbyselectiveNMDAreceptor antagonists suggestingthatTAAR1 activationmayenhance alsoglutamatergicfunction.Thereareseverallinesof evi-dence suggestingpro-cognitiveaction ofTAAR1agonistsin variousbehavioralexperimentalprotocolsandthereis ev-idence indicating that TAAR1 can modulatefrontal cortex glutamateNMDAreceptor– relatedfunctions[2,3,4,5]. Objectives:1.TostudyinvitrotheroleofTAAR1agonists onbasalcorticalglutamatergictransmissionandtheir ben-eficialeffectonAb-induceddysfunction.
2.Tostudy,invivo,theroleofTAAR1incognitive dysfunc-tioninducedbyAbandthebeneficialroleofTAAR1agonists oncognitioninAlzheimer’smousemodels.
Methods: Invitro experimentswereconductedonprimary cortical cultures.Cortices ofE17 embryo fromTAAR1 and controlmicewereisolatedandincubatedfor14daysat37°C and5%CO2.CellswerethenstimulatedwithAb1-42(1μM, AnaSpec, USA),TAAR1 agonist(RO5256390,Sigma Aldrich, Belgium, 1μM)orboth 1hrat37°C andNMDAsurface ex-pression wasassessed using biotinylation assay and West-ern blots. In vivo studies were performed using 10-weeks miceICVinjectedwith:Ab1-42(3μl),TAAR1agonist(3μl) or bothandvehicletreatedcontrols.7dayslater,aseries ofbehavioraltestswereperformedtoevaluatetheeffects ofAb1-42andTAAR1agonist,includingMorrisWaterMaze (MWM),novelobjectrecognition(NOR)andopenfield. Results: In vitro data showed that, as expected in WT mice, Ab 1-42significantly decreased NMDA surface(NR1: -35± 2.6%; NR2A: -38± 1.8%; NR2B: -47± 4.2%) expres-sionwhileTAAR1agonistpromotestheirmembrane localiza-tion (NR1: +48±4.8%;NR2A: +67±3.5%;NR2B:+52±3.8% p<0.05,Studentttest)oncorticalcells.
Conclusion: Altogether, our results showed that in vitro, TAAR1 agonistdisplayedtheabilityofincreasingNMDA re-ceptorssurfaceexpression,suggestingthepossibilityof dis-playingtherapeuticeffectoncognitiveAb induced impair-ments.Whethertheseeffectsarereproducibleinvivo,are currentlyaddressed.
References
[1] Selkoe,D.J.,2002.Alzheimer’sdiseaseisasynapticfailure. Sci-ence298(5594),789–791.
[2] Guise,K.G.,Shapiro,M.L.,2017.MedialPrefrontalCortex Re-ducesMemoryInterferencebyModifying Hippocampal Encod-ing.Neuron.94(1),183–1925.e8.
[3] Flores-Martínez,E.,Peña-Ortega,F.,2017.Amyloidb Peptide-InducedChangesinPrefrontalCortexActivityandItsResponse toHippocampalInput.Int.J.Pept.,7386809.
[4] Banks,P.J., Burroughs, A.C.,Barker,G.R., Brown,J.T., War-burton, E.C., Bashir, Z.I., 2015. Disruption of hippocampal-prefrontalcortexactivitybydopamineD2R-dependentLTDof
NMDAR transmission. Proc. Natl. Acad. Sci. USA. 112 (35), 11096–111011.
[5]Feld, M., Krawczyk, M.C., Sol Fustiñana, M., Blake, M.G., Baratti, C.M.,Romano, A., Boccia, M.M., 2014. Decreaseof ERK/MAPK overactivation in prefrontal cortex reverses early memory deficit in a mouse model ofAlzheimer’s disease. J. Alzheimers.Dis.40(1),69–82.
doi:10.1016/j.euroneuro.2019.09.487
P.480Theeffectsofpropolisextractonage-associated cognitivedeficitsinrats
S.S.Gocmez1 , ∗,G.Celebi1 ,T.Demirta¸s-¸Sahin1 ,E.Aksoz2 , T.Utkan1
1 Kocaeli University Faculty of Medicine, Department of
Pharmacology,Kocaeli,Turkey
2 Balikesir University Faculty of Medicine, Department of
Pharmacology,Balikesir,Turkey
Background:Propolis is widelyusedasalternative medic-inal product due to their antimicrobial, antiinflammatory and antioxidant properties. Previous studies have shown that propolis has a neuroprotective effect and alleviates thecognitiveimpairments inscopolamineorbeta-amyloid induced learning and memory impairment animal models [1,2]. The incidence of thephysiological agingassociated neurodegenerative diseases characterized bymemory loss anddementiaisincreasing.Theaimofthisstudyisto eval-uatetheeffectofchronicpropolisadministrationon cogni-tivedysfunctionsfollowingphysiologicalagingprocesses. Methods:Inthisstudy,maleWistarratsweredividedinto4 groups(n=10foreachgroup):young-control(YC-6months), young-propolis(YP-6months),old-control(OC-24months), old-propolis(OP-24 months). The water-soluble form of propoliswillbepreparedfromfreshTurkishpropolis (Aksu-vitalNaturalProductsCompany).The maincomponentsin thisextractwillbeidentifiedbyGasCromathography-Mass Spectrometry(GC-MS)analysis.Theextractofpropolis(100 mg/kg)wasadministeredorallyfor28consecutivedaysto YPandOPgroups.Attheendof28daysperiod,locomotor activities,passive avoidanceandelevated plusmazetests wereperformedrespectively.Inpassiveavoidance appara-tus,whichmeasuresemotionalmemory,acquisition(onday 1),andretention(onday2)trialswerecarriedout.In ac-quisitiontrial,an electric foot-shockwasdeliveredtothe animal via grid floor.The timetakenfor animals toenter thedarkcompartmentwasrecordedasthetraininglatency. Retentionlatencywasevaluated24-hafteracquisitiontrial. InEPMtest,whichmeasuresspatialmemory,acquisition(on day 1)andretention (onday 2)sessions were performed. Transferlatency(thetimeinwhichtheanimalmovesfrom theopenarmtotheenclosedarm)wasutilizedasanindex of learning and memory processes. The rats were placed intotheopenarmandthetransferlatencywasrecordedfor bothdays.Theresultsofthestudywereevaluatedbyone wayANOVAposthocTukeytest.Thedatawereconsidered tobesignificant statisticallyiftheprobabilityhadavalue of0.05orless.
S338 Abstracts Results:Thereisnostatisticallysignificantdifferences
be-tween thefirstday transferlatenciesin allgroups in pas-siveavoidanceandelevatedplusmazetests.Theretention latenciesinpassiveavoidancetestsignificantlyreducedin physiologically aged,OCgroup comparedtothe YCgroup (p<0.05). Also, the second day transfer latencies in ele-vated plus maze test increased in OC group compared to the young controls (p<0.05). The results of both behav-ioraltestsshownthedevelopmentofcognitivedysfunction because of the physiological aging.After chronic propolis administration,both latenciesinOPgroupreversedtothe youngcontrollevels.
Conclusion:The results ofthe studyhave shown thatthe chronic propolis extract administration may prevent the emotionalandspatialmemoryimpairmentduring physiolog-icalaging.Hencethepropolisextractcouldbeconsidered asanewstrategytopreventorslowdownthedevelopment ofcognitivedysfunctionsfollowingphysiologicalaging pro-cesses.However,furtherstudiesareneededtoexplorethe biologicalmechanismsofpropolisandtosupportthese find-ings.
References
[1]Nanaware, S., Shelar, M., Sinnathambi, A., Mahadik, K.R., Sathiyanarayanan, L., 2017.Neuroprotective effectofIndian propolisinbeta-amyloidinducedmemorydeficit:Impacton be-havioralandbiochemicalparametersinrats.Biomed. Pharma-cother.93,543–553.
[2]Chen,J.,Long,Y.,Han,M.,Wang,T.,Chen,Q.,Wang,R.,2017. Water-soluble derivative of propolis mitigates scopolamine-inducedlearningandmemoryimpairmentinmice.Pharmacol. Biochem.Behav.90,441–446.
doi:10.1016/j.euroneuro.2019.09.488
P.481Increasedrisk-takingbehaviourfollowingaloss by womenwith obesity is associated with ventrome-dialprefrontalcortexandinsulaalterations
T.Steward1 ,A.Juaneda-Segui2 , ∗,G.Mestre-Bach1 , I.Martínez-Zalacaín3 ,N.Vilarrasa4 ,J.M.Menchón2 , C.Soriano-Mas2 ,F.Fernandez-Aranda1
1 Bellvitge University Hospital-IDIBELL/CIBEROBN,
Depart-mentofPsychiatry,Barcelona,Spain
2 Bellvitge University Hospital-IDIBELL/CIBERSAM,
Depart-mentofPsychiatry,Barcelona,Spain
3 BellvitgeUniversityHospital-IDIBELL,Departmentof
Psy-chiatry,Barcelona,Spain
4 Bellvitge University Hospital-IDIBELL/CIBERDEM,
Depart-mentofEndocrinologyandNutrition,Barcelona,Spain Background:Obesityislinkedwithincreasedrisk-taking be-haviorintermsoffoodchoices. Multiplestudieshave sug-gestedthataltered activityin interoceptiveand decision-making circuitry may underlie the heightened risk-taking found in obesity. Whether this riskybehavior is driven by dysfunctionalsalienceprocessingor alackofappreciation ofdanger,orboth,remainsunclear.
Aim:Inthestudyathandweaimedtodescribethebrain re-gionspurportedlyunderpinningtheincreaserisk-taking
be-haviorinobesitybyassessingagroupofadultwomenwith obesityin comparisonwithhealthyweightcontrols during theperformanceofataskassessingriskbehaviorina food-independentcontext.
Methods: Twenty-three adult women with obesity and twenty-three age-matched, healthy weight controls com-pleted the Risky Gains Task during a 3T functional mag-netic resonance imaging scan. The Risky Gains Task con-sists of participantschoosing betweena safe option for a small,guaranteedmonetaryreward andriskyoptionswith largerrewardsbutalsoahigherchanceoflosingmoney.The frequency of risky choice overall and following a winning trial versus a losing trial were compared.Likewise, brain responsesduringwinningtrialsvs.loses,andduringriskvs. safedecisions(overallandfollowingwinningandlosing tri-als)werealsocomparedbetweenbothgroups.TheUPPS-P questionnaire wascompleted byall participants toassess impulsivitytraitlevels.
Results:Asexpected,thebodymassindex(BMI)ofthe obe-sity group (mean=43.59±6.98) was higher than the con-trol group (mean=20.93±6.98; p<0.001). Regarding psy-chometricassessments,therewerenosignificant between-groupdifferencesin UPPS-Pscores,although weobserved trending-level differences in particular UPPS-P subscales. Specifically,scoresinlackofperseverancetendedtobe re-ducedintheobesitygroup(p=0.07),whilescoresin sensa-tionseekingtendedtobehigherinobesesubjects(p=0.08). Neuroimaginganalysesdemonstratedthatparticipantswith obesityshoweddecreasedactivityin therightanterior in-suladuringlosingtrialsincomparisontothecontrolgroup (p<0.05, AlphaSim corrected), suggesting that the insula playsarole ingiving moreweighttopositive responseto rewardovertheimpactofaloss.Inaddition,rightinsula ac-tivationduringlosseswasnegativelycorrelatedwith UPPS-Psensationseekingscores(p=0.30,r=-0.320).Duringsafe trialsfollowingaloss,participantsintheobesegroup pre-senteddecreasedactivationintheventromedialprefrontal cortex(vmPFC) (p<0.05, AlphaSim corrected). vmPFC re-sponseduringpost-losstrialswaspositivelycorrelatedwith safer choices on the task overall (p=0.14, r=-0.371), in-dicating the vmPFC mayunderpin theassessment of risk-takingbehaviors.
Conclusions:Thebrainsofindividualswithobesitymaybe hyposensitivetointeroceptivecuesstemmingfromlosses, therebybringingabout increasedrisk-taking behaviors. In addition,disruptedtuningoftheinsulatowards interocep-tivesignalsmayleadtoalackofinputtothevmPFCwhen weighingthecostsandbenefitsofriskychoices.Thiscould partlyexplainwhyindividualswithobesityovereatdespite harmfuloutcomes.
doi:10.1016/j.euroneuro.2019.09.489
P.482Olfactoryneuronsassurrogatetissueto investi-gatedisordersofthebrain
J.Unterholzner1 , ∗,L.M.Steinmetz1 ,G.Besser2 ,S.Schulz3 , P.Michenthaler1 ,S.Kasper1 ,A.Spittler4 , 5 ,C.A.Mueller2 , R.Lanzenberger1
1 Medical University of Vienna, Department of Psychiatry
