grant
Cannabinoid inhibition of CNS inflammasome activation via modulation of the gut-brain axis
Organization UNIVERSITY OF NEBRASKA MEDICAL CENTERLocation OMAHA, UNITED STATESPosted 15 Apr 2025Deadline 28 Feb 2030
NIHUS FederalResearch GrantFY202618-FDG18F- FDG18FDG2 Fluoro 2 deoxy D glucose2,3,7,8-Tetrachlorodibenzo-p-dioxin Receptors2-Fluoro-2-deoxyglucose9-ene-TetrahydrocannabinolAH ReceptorsAIDS VirusAIDS progressionAIDS/HIVAcquired Immune Deficiency Syndrome VirusAcquired Immunodeficiency Syndrome VirusAffectAgonistAlimentary CanalAminoacetic AcidAnti-InflammatoriesAnti-Inflammatory AgentsAnti-inflammatoryApoptosis-Related Cysteine Protease Caspase 1ApoptoticAryl Hydrocarbon ReceptorAutophagocytosisAutopsyBBB crossingBS-seqBasal GangliaBasal NucleiBehaviorBeta Proprotein Interleukin 1BindingBisulfite-based sequencingBlood PlasmaBlood monocyteBrainBrain Nervous SystemCASP-1CASP1CASP1 geneCB1CB1 ReceptorCB1RCB2CB2 ReceptorCB2RCNR1 geneCNR2CNR2 geneCannabinoid Receptor CB1Cannabinoid Receptor CB2CannabinoidsCaspaseCaspase GeneCaspase-1Caspase-1 GeneCell Communication and SignalingCell DeathCell SignalingCell-Death ProteaseCellular Immune FunctionCellular StressCellular Stress ResponseChemicalsChronicCocaineCocaine use disorderColonCysteine EndopeptidasesCysteine ProteaseCysteine ProteinasesD9-tetrahydrocannabinolDNADNA MethylationDataDegenerative Neurologic DisordersDelta-9-TetrahydrocannabinolDeoxyribonucleic AcidDevelopmentDiagnosisDigestive TractDioxin ReceptorsDioxygenasesDiseaseDisease ProgressionDisorderDoseDrugsEncephalonEpigeneticEpigenetic ChangeEpigenetic MechanismEpigenetic ProcessEpithelial CellsEpitheliumFamilyGI TractGastrointestinal TractGastrointestinal tract structureGene ExpressionGenesGlycineHIVHIV 1 associated neurocognitive disorderHIV associated neurocognitive deficitHIV associated neurocognitive impairmentHIV disease progressionHIV individualsHIV induced neurocognitive deficitHIV induced neurocognitive impairmentHIV infected individualsHIV infected personsHIV neurocognitive impairmentHIV peopleHIV positive individualsHIV positive peopleHIV progressionHIV-1 associated neurocognitive deficitHIV-1 associated neurocognitive disorderHIV-1 associated neurocognitive impairmentHIV-1 disease progressionHIV-associated neurocognitive disorderHIV/AIDSHIV/AIDS progressionHigh PrevalenceHortega cellHumanHuman Immunodeficiency VirusesHypermethylationICE ProteaseICE-like proteaseIFNIFN-Gamma-Inducing Factor GeneIFN-gamma-Inducing FactorIGIFIGIF GeneIL-1 GammaIL-1 Gamma GeneIL-1 betaIL-1 beta ConvertaseIL-1 beta-Converting EnzymeIL-1 βIL-1-bIL-18IL-18 GeneIL-1BCIL-1b Converting EnzymeIL-1gIL-1g GeneIL-1βIL1-BetaIL1-βIL18IL18 ProteinIL18 geneIL1B ProteinIL1B-ConvertaseIL1BCIL1BCEIL1F2IL1F4IL1F4 GeneIL1βImmune Cell ActivationImmune DiseasesImmune DisordersImmune DysfunctionImmune System DiseasesImmune System DisorderImmune System DysfunctionImmune System and Related DisordersImmunofluorescenceImmunofluorescence ImmunologicImmunologic DiseasesImmunological DiseasesImmunological DysfunctionImmunological System DysfunctionImmunomodulationIn VitroIndividualIndolesInfectionInflammasomeInflammationInflammatoryInflammatory ResponseInnate Immune ResponseInterferon-Gamma-Inducing Factor GeneInterferon-gamma-Inducing FactorInterferonsInterleukin 1-B Converting EnzymeInterleukin 1-Beta ConvertaseInterleukin 18 (Interferon-Gamma-Inducing Factor)Interleukin 18 (Interferon-Gamma-Inducing Factor) GeneInterleukin 18 ProproteinInterleukin 18 Proprotein GeneInterleukin 1betaInterleukin-1 Beta Converting EnzymeInterleukin-1 Converting EnzymeInterleukin-1 GammaInterleukin-1 Gamma GeneInterleukin-1 betaInterleukin-18Interleukin-18 PrecursorInterleukin-18 Precursor GeneInterleukin-1βInterventionIntestinalIntestinesIntracellular Communication and SignalingLAV-HTLV-IIILevarterenolLevonorepinephrineLinkLymphadenopathy-Associated VirusMEFV gene productMGC12320MGC12320 GeneMacromolecular Protein ComplexesMarrow monocyteMediatingMedicationMessenger RNAMiceMice MammalsMicrogliaModern ManMolecularMolecular InteractionMultiprotein ComplexesMurineMusNervous System Degenerative DiseasesNeural Degenerative DiseasesNeural degenerative DisordersNeurocognitive Impairment in HIVNeurocognitive Impairment in HIV-1Neurodegenerative DiseasesNeurodegenerative DisordersNeurologic Degenerative ConditionsNeurologic DysfunctionsNoradrenalineNorepinephrineNuclear TranslocatorOrganPET/CTPET/CT scanPLWHPWHPathogenesisPathogenicityPathway interactionsPharmaceutical PreparationsPlasmaPlasma SerumPolyaromatic Hydrocarbon ReceptorsPreinterleukin 1 BetaProductionProgress into acquired immunodeficiency syndromeProgress to acquired immunodeficiency syndromeProgression in HIVProgression in HIV-1Progression to AIDSProgression towards AIDSPropertyPropionatesProteobacteriaPurple BacteriaRIP1RIP3RIPK1RIPK1 geneRIPK3RIPK3 geneReceptor ProteinReceptor-Interacting Protein 3Receptor-Interacting Serine/Threonine Kinase 1Receptor-Interacting Serine/Threonine Protein Kinase 3Reticuloendothelial System, Serum, PlasmaRisk FactorsSIVSignal TransductionSignal Transduction SystemsSignalingSignaling Factor Proto-OncogeneSignaling Pathway GeneSignaling ProteinSimian Immunodeficiency VirusesSiteT-CellsT-LymphocyteTCDD ReceptorsTestingTetTetanus Helper PeptideTetrahydrocannabinolTherapeuticTransmissionUpregulationViralVirus-HIVacquired immunodeficiency syndrome progressionaddictionaddictive disorderalimentary tractantiretroviral therapyantiretroviral treatmentautophagybiological signal transductionbisulfite sequencingbisulfite-seqblood-brain barrier crossingbloodbrain barrier crossingbowelcannabinoid receptor 1cannabinoid receptor 2cannabinoid receptor type 1cannabinoid receptor type 2cannabinoid type 1cell stresschallenge in rhesus macaquesco-morbidco-morbiditycocaine usecomorbiditycystein proteasecystein proteinasecysteine endopeptidasedegenerative diseases of motor and sensory neuronsdegenerative neurological diseasesdelta(1)-THCdelta(1)-Tetrahydrocannabinoldelta(9)-THCdelta(9)-Tetrahydrocannabinoldevelopmentaldigestive canaldrug/agentdysbacteriosisdysbiosisdysbioticepigenetic regulationepigeneticallyfluorodeoxyglucosegitter cellgut dysbiosisgut to brain axisgut-brain axisgut-brain communicationgut-brain interactionsgut-brain relationshipgut-brain signalinghuman immunodeficiency virus progressionimmune activationimmune functionimmune modulationimmune regulationimmunologic reactivity controlimmunomodulatoryimmunoregulationimmunoregulatoryindividuals infected with HIVindividuals with HIVindividuals with human immunodeficiency virusinfected rhesus macaquesinfected rhesus monkeyinfection in rhesus macaquesinfection of rhesus macaquesinhibitorlipophilicitymRNAmarenostrinmesogliamicrobialmicrobial imbalancemicrobiota-gut-brain axismicrobiota-gut-brain interactionsmicrobiota-gut-brain signalingmicroglial cellmicrogliocytemonocytenecrocytosisnecropsyneural inflammationneurodegenerative illnessneuroinflammationneuroinflammatoryneurological dysfunctionneuroprotectionneuroprotectivepathwaypeople infected with HIVpeople infected with human immunodeficiency viruspeople living with HIVpeople with HIVpeople with human immunodeficiency virusperivascular glial cellpositron emission computed tomographypostmortempreventpreventingprogression to acquired immunodeficiency syndromepromoterpromotorprotein expressionpsychostimulantpyrinreceptorrhesus challengerhesus macaque challengerhesus monkey infectiontherapy adherencetherapy compliancethymus derived lymphocytetransmission processΔ(1)-THCΔ(1)-tetrahydrocannabinolΔ(9)-THCΔ(9)-tetrahydrocannabinolΔ-9-tetrahydrocannabinolΔ9-tetrahydrocannabinol
Description preview
ABSTRACT
The primary objective of this proposal is to investigate Cocaine/HIV/SIV induced changes in inflammasome
activation and their epigenetic regulation in the intestine and brain and its modulation by long-term, low-dose
cannabinoids and combination antiretroviral therapy. The NLRP3 (NOD-like receptor family, pyrin domain
containing)…
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