2025
Deuterium MRS for In Vivo Measurement of Lipogenesis in the Liver
Gursan A, de Graaf R, Thomas M, Prompers J, De Feyter H. Deuterium MRS for In Vivo Measurement of Lipogenesis in the Liver. NMR In Biomedicine 2025, 38: e70014. PMID: 39994887, DOI: 10.1002/nbm.70014.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDeuteriumLipogenesisLiverMagnetic Resonance SpectroscopyMaleRatsRats, Sprague-DawleyConceptsH-MRSHepatic DNLMRS dataLiver tissueMeasurement of lipogenesisDietary interventionLiver lipidsHepatic de novo lipogenesisLow density lipoproteinDetection of deuteriumGold standard measureMetabolic diseasesIncreased hepatic DNLLiverDensity lipoproteinDrinking waterDeuterium labelingIn vivo measurementsNMR dataExcised liver tissueTissueDeuteriumMRSMethylene resonancesDeuterated waterPrefrontal 5α-reductase 2 mediates male-specific acute stress response
Cadeddu R, Braccagni G, Floris G, Branca C, Corridori E, Salviati S, Sánchez P, Santovito L, Torres J, Ortega E, Pinna G, Moos P, Scheggi S, Bortolato M. Prefrontal 5α-reductase 2 mediates male-specific acute stress response. Science Advances 2025, 11: eadr0563. PMID: 39841836, PMCID: PMC11753402, DOI: 10.1126/sciadv.adr0563.Peer-Reviewed Original ResearchConceptsMedial prefrontal cortexStress reactivityAcute stressAcute stress reactivitySexually dimorphic effectsAcute stress responsePrefrontal cortexStress responseNeurosteroid allopregnanoloneReduced stress responseDimorphic effectsBrain synthesisKnockdown ratsKnockout ratsAllopregnanoloneAP synthesisRatsSingle-nucleus transcriptomesCortexNeurosteroidsDown-regulationIncreased levelsMaleStressResponseL-type calcium channel blockade attenuates the anxiogenic-like effects of cocaine abstinence in female and male rats
Nunes E, Kimble V, Rajadhyaksha A, Addy N. L-type calcium channel blockade attenuates the anxiogenic-like effects of cocaine abstinence in female and male rats. Neuroscience 2025, 568: 314-322. PMID: 39761823, DOI: 10.1016/j.neuroscience.2025.01.003.Peer-Reviewed Original ResearchThis study found that isradipine reduces anxiety and depression-like symptoms during cocaine withdrawal in rats, suggesting potential treatment for mood disorders in addiction.
2024
Molecular mechanism governing the plasticity of use-dependent spike broadening in dorsal root ganglion neurons
Alexander T, Tymanskyj S, Kennedy K, Kaczmarek L, Covarrubias M. Molecular mechanism governing the plasticity of use-dependent spike broadening in dorsal root ganglion neurons. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 122: e2411033121. PMID: 39739796, PMCID: PMC11725888, DOI: 10.1073/pnas.2411033121.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsGanglia, SpinalNeuronal PlasticityNeuronsPhosphorylationRatsRats, Sprague-DawleyShaw Potassium ChannelsConceptsN-terminal inactivation domainDorsal root ganglionDorsal root ganglion neuronsSpike broadeningCumulative inactivationVoltage-gated K<sup>+</sup>Rat dorsal root ganglionViral vector approachPain modulationRoot ganglionGanglion neuronsKv3.4AP widthAction potentialsDynamic clampMechanosensory transductionInactivation domainNeuronsMolecular mechanismsFast recoveryInactivationSlow recoveryPhosphorylationPainRepolarizationEfficacy of GABA aminotransferase inactivator OV329 in models of neuropathic and inflammatory pain without tolerance or addiction
Wirt J, Ferreira L, Jesus C, Woodward T, Oliva I, Xu Z, Crystal J, Pepin R, Silverman R, Hohmann A. Efficacy of GABA aminotransferase inactivator OV329 in models of neuropathic and inflammatory pain without tolerance or addiction. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 122: e2318833121. PMID: 39793055, PMCID: PMC11725897, DOI: 10.1073/pnas.2318833121.Peer-Reviewed Original ResearchConceptsComplete Freund's adjuvantInflammatory painMechanical hypersensitivityAntinociceptive efficacyGlutamate levelsInjection of complete Freund's adjuvantConditioned place preference assayPaclitaxel-induced mechanical hypersensitivitySpinal site of actionSide effectsEnhancement of GABAergic transmissionChemotherapeutic agent paclitaxelPaclitaxel-induced increaseCompared to morphineLumbar spinal cordIncreased endogenous GABA levelsReduced glutamate levelsNeuropathic nociceptionSite of actionGABAergic transmissionAnalgesic strategiesPathological painGABAergic inhibitionSpinal sitesAbuse liabilityNeuroinflammatory history results in overlapping transcriptional signatures with heroin exposure in the nucleus accumbens and alters responsiveness to heroin in male rats
Floris G, Zanda M, Dabrowski K, Daws S. Neuroinflammatory history results in overlapping transcriptional signatures with heroin exposure in the nucleus accumbens and alters responsiveness to heroin in male rats. Translational Psychiatry 2024, 14: 500. PMID: 39702361, PMCID: PMC11659471, DOI: 10.1038/s41398-024-03203-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBehavior, AnimalHeroinLipopolysaccharidesMaleNeuroinflammatory DiseasesNucleus AccumbensRatsRats, Sprague-DawleyTranscriptomeConceptsResponse to heroinNucleus accumbensHeroin exposureOpioid use disorderSelf-administrationHeroin self-administrationMesolimbic dopamine systemOpioid-induced behaviorsMolecular neuroadaptationsDopamine systemOpioid rewardHeroin intakeBehavioral effectsUse disorderPsychiatric researchLipopolysaccharide (LPS)-induced neuroinflammationPreclinical modelsBehavioral ramificationsSensitivity to opioidsOpioid heroinHeroinMale ratsAccumbensHeightened immune responseNeuroinflammationSGLT2 inhibition alters substrate utilization and mitochondrial redox in healthy and failing rat hearts
Goedeke L, Ma Y, Gaspar R, Nasiri A, Lee J, Zhang D, Galsgaard K, Hu X, Zhang J, Guerrera N, Li X, LaMoia T, Hubbard B, Haedersdal S, Wu X, Stack J, Dufour S, Butrico G, Kahn M, Perry R, Cline G, Young L, Shulman G. SGLT2 inhibition alters substrate utilization and mitochondrial redox in healthy and failing rat hearts. Journal Of Clinical Investigation 2024, 134: e176708. PMID: 39680452, PMCID: PMC11645152, DOI: 10.1172/jci176708.Peer-Reviewed Original ResearchConceptsSodium-glucose cotransporter type 2Heart failureKetone oxidationGas chromatography-mass spectrometryFatty acid oxidationLeft ventricular ejection fractionReduced myocardial oxidative stressVentricular ejection fractionKetone supplementationWeeks of treatmentMyocardial oxidative stressDecreased pyruvate oxidationInduce heart failurePlasma glucose levelsIn vivo effectsSGLT2i treatmentEjection fractionAssociated with improvementsAwake ratsSGLT2 inhibitionCardioprotective benefitsLiquid chromatography-tandem mass spectrometryPlasma ketonesRates of ketonizationChromatography-tandem mass spectrometryIntrathecal lactate dehydrogenase A inhibitors FX11 and oxamate alleviate chronic constriction injury-induced nociceptive sensitization through neuroinflammation and angiogenesis
Cheng H, Chen N, Chen W, Wu Z, Sun Y, Teng W, Su F, Sung C, Wen Z. Intrathecal lactate dehydrogenase A inhibitors FX11 and oxamate alleviate chronic constriction injury-induced nociceptive sensitization through neuroinflammation and angiogenesis. The Journal Of Headache And Pain 2024, 25: 207. PMID: 39587478, PMCID: PMC11590346, DOI: 10.1186/s10194-024-01916-x.Peer-Reviewed Original ResearchConceptsLactate dehydrogenase ANeuropathic painNociceptive sensitizationLDHA inhibitorsTreat neuropathic painType of painUpregulation of glycolysisCCI-induced neuroinflammationCentral nervous systemBackgroundNeuropathic painNeuropathic ratsSpinal roleNociceptive behaviorBlood vessel growthImmunohistochemical analysisControl inflammationPainEffective treatmentConclusionIn conclusionHIF-1aCellular mechanismsNervous systemTherapeutic targetVessel growthWestern blottingProteomic Profile of Circulating Extracellular Vesicles in the Brain after Δ9-Tetrahydrocannabinol Inhalation
Lallai V, Lam T, Garcia-Milian R, Chen Y, Fowler J, Manca L, Piomelli D, Williams K, Nairn A, Fowler C. Proteomic Profile of Circulating Extracellular Vesicles in the Brain after Δ9-Tetrahydrocannabinol Inhalation. Biomolecules 2024, 14: 1143. PMID: 39334909, PMCID: PMC11430348, DOI: 10.3390/biom14091143.Peer-Reviewed Original ResearchConceptsImmediate early gene c-fosChronic THC exposureEarly gene c-fosCannabinoid 1 receptorGene c-fosSex-specific mannerTHC exposurePsychoactive componentExtracellular vesiclesCentral signaling mechanismDrug effectsTHCChoroid plexus epithelial cellsFemale ratsC-fosPlexus epithelial cellsBrainCannabisRelease of EVsRegulate intercellular communicationCerebrospinal fluidEpithelial cellsIntercellular signaling mediatorsEV signalingIntercellular communicationHigh-fat diet, microbiome-gut-brain axis signaling, and anxiety-like behavior in male rats
de Noronha S, de Moraes L, Hassell J, Stamper C, Arnold M, Heinze J, Foxx C, Lieb M, Cler K, Karns B, Jaekel S, Loupy K, Silva F, Chianca-Jr. D, Lowry C, de Menezes R. High-fat diet, microbiome-gut-brain axis signaling, and anxiety-like behavior in male rats. Biological Research 2024, 57: 23. PMID: 38705984, PMCID: PMC11071217, DOI: 10.1186/s40659-024-00505-1.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnxietyBehavior, AnimalBrain-Gut AxisDiet, High-FatGastrointestinal MicrobiomeMaleObesityRatsRats, Sprague-DawleySignal TransductionConceptsDefensive behavioral responsesSerotonergic gene expressionDorsal raphe nucleusSlc6a4 mRNA expressionBehavioral responsesMicrobiome-gut-brainRaphe nucleusAnxiety-related behavioral responsesBrain serotonergic systemSerotonergic brain systemAnxiety-like behaviorMale ratsAxis signalingHigh-fat dietBrain systemsSerotonergic systemAssociated with stressCommunity compositionGut microbiomeGene expressionAbundance of BlautiaHTR1AGut microbiome diversityTPH2SLC6A4TRPM7 facilitates fibroblast-like synoviocyte proliferation, metastasis and inflammation through increasing IL-6 stability via the PKCα-HuR axis in rheumatoid arthritis
Lin Y, Chen Y, Hu W, Liu X, Hao W, Xing J, Ding J, Xu Y, Yao F, Zhao Y, Wang K, Li S, Yu Q, Hu W, Zhou R. TRPM7 facilitates fibroblast-like synoviocyte proliferation, metastasis and inflammation through increasing IL-6 stability via the PKCα-HuR axis in rheumatoid arthritis. International Immunopharmacology 2024, 132: 111933. PMID: 38581988, DOI: 10.1016/j.intimp.2024.111933.Peer-Reviewed Original ResearchConceptsTransient receptor potential melastatin 7Rheumatoid arthritisInhibition of transient receptor potential melastatin 7Human RA patientsSynovial hyperplasiaAdjuvant-induced arthritis ratsIncreased TRPM7 expressionIL-6 mRNATreatment of RAPathogenesis of RAFibroblast-like synoviocytesTRPM7 silencingProgression of rheumatoid arthritisTRPM7 expressionChannel inhibitionCation channelsRA patientsMetastasisPharmacological inhibitionArthritis ratsInflammationNuclear translocationSynoviocyte proliferationHyperplasiaProliferationThe Neuroprotective Role of Quinoa (Chenopodium quinoa, Wild) Supplementation in Hippocampal Morphology and Memory of Adolescent Stressed Rats
Terreros G, Pérez M, Muñoz-LLancao P, D’Espessailles A, Martínez E, Dagnino-Subiabre A. The Neuroprotective Role of Quinoa (Chenopodium quinoa, Wild) Supplementation in Hippocampal Morphology and Memory of Adolescent Stressed Rats. Nutrients 2024, 16: 381. PMID: 38337665, PMCID: PMC10857380, DOI: 10.3390/nu16030381.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChenopodium quinoaDietary SupplementsHippocampusMaleMaze LearningRatsRats, Sprague-DawleyStress, PsychologicalConceptsStressed ratsInfluence anxiety-like behaviorStress-induced dendritic atrophyVulnerability to chronic stressRat chowAnxiety-like behaviorChronically stressed ratsRestraint stress protocolNon-stressedLocomotor activitySpatial memoryY-mazeCognitive performanceHippocampal morphologyMale Sprague-Dawley ratsDendritic atrophyChronic stressPrepubertal male Sprague-Dawley ratsStress protocolNeuroprotective roleSprague-Dawley ratsDendritic lengthCA3 areaPyramidal neuronsBrain physiology
2023
Lysophosphatidic acid triggers inflammation in the liver and white adipose tissue in rat models of 1-acyl-sn-glycerol-3-phosphate acyltransferase 2 deficiency and overnutrition
Sakuma I, Gaspar R, Luukkonen P, Kahn M, Zhang D, Zhang X, Murray S, Golla J, Vatner D, Samuel V, Petersen K, Shulman G. Lysophosphatidic acid triggers inflammation in the liver and white adipose tissue in rat models of 1-acyl-sn-glycerol-3-phosphate acyltransferase 2 deficiency and overnutrition. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2312666120. PMID: 38127985, PMCID: PMC10756285, DOI: 10.1073/pnas.2312666120.Peer-Reviewed Original ResearchUse of a polymeric implant system to assess the neurotoxicity of subacute exposure to 2,2′,5,5′-tetrachlorobiphenyl-4-ol, a human metabolite of PCB 52, in male adolescent rats
Wang H, Bullert A, Li X, Stevens H, Klingelhutz A, Ankrum J, Adamcakova-Dodd A, Thorne P, Lehmler H. Use of a polymeric implant system to assess the neurotoxicity of subacute exposure to 2,2′,5,5′-tetrachlorobiphenyl-4-ol, a human metabolite of PCB 52, in male adolescent rats. Toxicology 2023, 500: 153677. PMID: 37995827, PMCID: PMC10757425, DOI: 10.1016/j.tox.2023.153677.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAnimalsChildHumansMaleNeoplasmsNeurotoxicity SyndromesPolychlorinated BiphenylsRatsRats, Sprague-DawleyTandem Mass SpectrometryConceptsPersistent organic pollutantsPolychlorinated biphenylsPolymeric implantsDrug delivery systemsPCB 52Tandem mass spectrometryOrganic pollutantsMass spectrometryGas chromatographySustained releaseDelivery systemHuman metabolitesHole-board testAdolescent Sprague DawleyMale adolescent ratsAnxiety-like behaviorOpen field testLoading concentrationStraightforward methodHydroxylated metabolitesSubacute neurotoxicitySubacute exposureImmune inhibitionNeurotoxic outcomesSprague-DawleyThe Sympathetic Nervous System Promotes Hepatic Lymphangiogenesis, which Is Protective Against Liver Fibrosis
Tanaka M, Jeong J, Thomas C, Zhang X, Zhang P, Saruwatari J, Kondo R, McConnell M, Utsumi T, Iwakiri Y. The Sympathetic Nervous System Promotes Hepatic Lymphangiogenesis, which Is Protective Against Liver Fibrosis. American Journal Of Pathology 2023, 193: 2182-2202. PMID: 37673329, PMCID: PMC10699132, DOI: 10.1016/j.ajpath.2023.08.004.Peer-Reviewed Original ResearchConceptsPartial portal vein ligationNoncirrhotic portal hypertensionCirrhotic patientsVascular endothelial growth factorLiver fibrosisEndothelial growth factorPortal hypertensionSympathetic denervationSympathetic nervesBDL ratsVascular diseaseIdiopathic noncirrhotic portal hypertensionGrowth factorPortal hypertensive patientsPortal vein ligationSympathetic nervous systemMechanisms of lymphangiogenesisCeliac ganglionectomyHypertensive patientsLymphatic vessel numberLiver biopsyLiver cirrhosisVein ligationPPVL ratsHepatic lymphatic vesselsVoltage-gated potassium channels control extended access cocaine seeking: a role for nucleus accumbens astrocytes
Xia M, Anderson T, Prantzalos E, Hawkinson T, Clarke H, Keohane S, Sun R, Turner J, Ortinski P. Voltage-gated potassium channels control extended access cocaine seeking: a role for nucleus accumbens astrocytes. Neuropsychopharmacology 2023, 49: 551-560. PMID: 37660129, PMCID: PMC10789875, DOI: 10.1038/s41386-023-01718-w.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAstrocytesCocaineDopamineNucleus AccumbensPotassium Channels, Voltage-GatedRatsRats, Sprague-DawleyConceptsNucleus accumbens shellNAc astrocytesCocaine self-administration trainingCocaine-associated behaviorsReward-related learningSelf-administration trainingImpact of dopamineCocaine-seekingAccumbens shellDopaminergic signalingBehavioral effectsDopamine levelsCocaineInhibition of Kv7 channelsIntracellular Ca2+ transientsDopamineAstrocytic Ca2+ signalingExogenous dopamineBehavioral implicationsCa2+ transientsDrug useCa2+ imagingVoltage-gated channel activityPotassium channel functionCa2+ signalingEvaluation of toxicity profile of kratom (Mitragyna speciosa Korth) decoction in rats
Hassan Z, Singh D, Suhaimi F, Chear N, Harun N, See C, Kaur G, Mat N, Bakar S, Yusof N, Kasinather V, Chawarski M, Murugaiyah V, Ramanathan S. Evaluation of toxicity profile of kratom (Mitragyna speciosa Korth) decoction in rats. Regulatory Toxicology And Pharmacology 2023, 143: 105466. PMID: 37536550, DOI: 10.1016/j.yrtph.2023.105466.Peer-Reviewed Original ResearchConceptsDays of treatmentToxicity profileFemale Sprague-Dawley ratsOpioid replacement therapyLow platelet countEnd of treatmentSprague-Dawley ratsEvidence of toxicityOccurrence of mortalityPlatelet countDawley ratsHematology profileBody weightMitragyna speciosa KorthBrain tissueHistopathology analysisHistological investigationHerbal drug preparationsDecoctionUric acidDrug preparationTherapeutic propertiesKidneyMortalityRatsTherapeutic efficacy of intravenous infusion of mesenchymal stem cells in rat perinatal brain injury
Terada K, Sasaki M, Nagahama H, Kataoka-Sasaki Y, Oka S, Ukai R, Yokoyama T, Iizuka Y, Sakai T, Fukumura S, Tsugawa T, Kocsis J, Honmou O. Therapeutic efficacy of intravenous infusion of mesenchymal stem cells in rat perinatal brain injury. Pediatric Research 2023, 94: 1921-1928. PMID: 37422495, DOI: 10.1038/s41390-023-02717-9.Peer-Reviewed Original ResearchConceptsPerinatal brain injuryBrain injuryMesenchymal stem cellsIntravenous infusionVehicle groupBrain volumeTherapeutic efficacyInfused mesenchymal stem cellsLeft common carotid arteryHistological analysisNon-ischemic hemispherePostnatal day 7Common carotid arteryEmbryonic day 18Stem cellsHypoxia-ischemiaMSC infusionPreterm infantsGABAergic cellsNeurological functionSignificant complicationsCortical synapsesFunctional improvementCarotid arteryIntravenous administrationGene and protein expression and metabolic flux analysis reveals metabolic scaling in liver ex vivo and in vivo
Akingbesote N, Leitner B, Jovin D, Desrouleaux R, Owusu D, Zhu W, Li Z, Pollak M, Perry R. Gene and protein expression and metabolic flux analysis reveals metabolic scaling in liver ex vivo and in vivo. ELife 2023, 12: e78335. PMID: 37219930, PMCID: PMC10205083, DOI: 10.7554/elife.78335.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsLiverMetabolic Flux AnalysisMiceMice, Inbred C57BLOxygen ConsumptionRatsRats, Sprague-DawleyConceptsMetabolic scalingMetabolic fluxMetabolic processesBody sizeMitochondrial metabolic processesMultiple cellular compartmentsVivo metabolic fluxesLevel of genesKey metabolic pathwaysProtein expressionMetabolic flux analysisAspects of metabolismCellular compartmentsGene expressionDifferential expressionMetabolic pathwaysGenesFlux analysisOxidative damageEnzyme activitySubstrate supplyFold rangeSpeciesExpressionMetabolic rateOrbitofrontal cortex microRNAs support long-lasting heroin seeking behavior in male rats
Zanda M, Floris G, Daws S. Orbitofrontal cortex microRNAs support long-lasting heroin seeking behavior in male rats. Translational Psychiatry 2023, 13: 117. PMID: 37031193, PMCID: PMC10082780, DOI: 10.1038/s41398-023-02423-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCravingCuesDrug-Seeking BehaviorHeroinMaleMicroRNAsOpioid-Related DisordersPrefrontal CortexRatsRats, Sprague-DawleySelf AdministrationConceptsOpioid use disorderOrbitofrontal cortexHL animalsHeroin seekingDrug cravingSelf-administer heroinLong-term heroinMaintenance of abstinenceDrug seeking behaviorOpioid useHeroin cravingMale ratsPreclinical studiesUse disordersDrug useExposure paradigmBrain regionsAbstinence periodAbstinenceHeroinDrug cuesSeeking behaviourLow dosageCravingProteomic analysis
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