2025
Uric Acid Stroke Cerebroprotection Transcended Sex, Age, and Comorbidities in a Multicenter Preclinical Trial
Patel R, Kumskova M, Kodali H, Budnik I, Kuznetsov V, Jain A, Jha A, Thedens D, Dhanesha N, Sutariya B, Nagarkatti K, Lamb J, Kamat P, Shi Y, Avery B, Imai T, Jin X, Chauhan A, Boisserand L, Khan M, Dhandapani K, Sanganahalli B, Sansing L, Hess D, Koehler R, McCullough L, Aronowski J, Ayata C, Diniz M, Lyden P, Planas A, Chamorro A, Chauhan A, Leira E, Investigators O. Uric Acid Stroke Cerebroprotection Transcended Sex, Age, and Comorbidities in a Multicenter Preclinical Trial. Stroke 2025, 56: 965-973. PMID: 40091742, PMCID: PMC11932773, DOI: 10.1161/strokeaha.124.048748.Peer-Reviewed Original ResearchConceptsUA-treated animalsPrimary functional outcomeFunctional outcomesMiddle cerebral artery filament occlusionModified intention-to-treat populationIntention-to-treat populationUric acidHuman clinical trialsImprove functional outcomesStudy drugIntravenous salineEffects of UARelevant to patientsClinical trialsPrimary outcomeSaline controlsSecondary outcomesPreclinical trialsDay 2Survival rateDay 7Filament occlusionGroups of animalsComorbiditiesDiverse comorbiditiesDrugging Disordered Proteins by Conformational Selection to Inform Therapeutic Intervention
Bogin B, Levine Z. Drugging Disordered Proteins by Conformational Selection to Inform Therapeutic Intervention. Journal Of Chemical Theory And Computation 2025, 21: 3204-3215. PMID: 40029731, DOI: 10.1021/acs.jctc.4c01160.Peer-Reviewed Original ResearchConceptsIslet amyloid polypeptideIntrinsically disordered proteinsConformational selectionDisordered proteinsHuman islet amyloid polypeptideMolecular dynamics simulationsStable binding sitesSelf-assembling sequencesIAPP sequenceFixed conformationAmyloid polypeptideUmbrella samplingBinding preferencesConformational specificityTwo-state modelDynamics simulationsConformational heterogeneityNew conformationsBinding sitesMolecular binding mechanismsConformationBinding mechanismFoldamersStructural conformationProteinDeuterium 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 ResearchConceptsH-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 waterIncreasing rat numbers in cities are linked to climate warming, urbanization, and human population
Richardson J, McCoy E, Parlavecchio N, Szykowny R, Beech-Brown E, Buijs J, Buckley J, Corrigan R, Costa F, DeLaney R, Denny R, Helms L, Lee W, Murray M, Riegel C, Souza F, Ulrich J, Why A, Kiyokawa Y. Increasing rat numbers in cities are linked to climate warming, urbanization, and human population. Science Advances 2025, 11: eads6782. PMID: 39888984, PMCID: PMC11784805, DOI: 10.1126/sciadv.ads6782.Peer-Reviewed Original ResearchConceptsRat numbersHuman populationSeasonal activity periodFuture management strategiesMitigation needsFood availabilityFuture vulnerabilityLong-term trendsPublic complaintsBiological impactClimate warmingEnvironmental changesWarmer temperaturesCommensal pestsManagement strategiesCityRat populationsWashington D.C.Estimate trendsUrbanizationNew YorkUrban ratsActive periodIncreasing trendWarmingBridging animal models and humans: neuroimaging as intermediate phenotypes linking genetic or stress factors to anhedonia
Guo H, Xiao Y, Dong S, Yang J, Zhao P, Zhao T, Cai A, Tang L, Liu J, Wang H, Hua R, Liu R, Wei Y, Sun D, Liu Z, Xia M, He Y, Wu Y, Si T, Womer F, Xu F, Tang Y, Wang J, Zhang W, Zhang X, Wang F. Bridging animal models and humans: neuroimaging as intermediate phenotypes linking genetic or stress factors to anhedonia. BMC Medicine 2025, 23: 38. PMID: 39849528, PMCID: PMC11755933, DOI: 10.1186/s12916-025-03850-4.Peer-Reviewed Original ResearchConceptsIntermediate phenotypesCore symptoms of depressionAmplitude of low-frequency fluctuationNeuroimaging patternsSubtypes of depressionCore depressive symptomsExpression of risk genesDiverse clinical populationsSymptoms of depressionRodent modelsAssociated with depressionLow-frequency fluctuationsStress-related changesDepression subtypesCore symptomsCross-species validationPsychiatric disordersNeuropsychiatric disordersDepressive symptomsBehavioral manifestationsStress modelDepression cohortClinical populationsSensorimotor regionsAnhedoniaContextual cues facilitate dynamic value encoding in the mesolimbic dopamine system
Fraser K, Collins V, Wolff A, Ottenheimer D, Bornhoft K, Pat F, Chen B, Janak P, Saunders B. Contextual cues facilitate dynamic value encoding in the mesolimbic dopamine system. Current Biology 2025, 35: 746-760.e5. PMID: 39855205, PMCID: PMC11859769, DOI: 10.1016/j.cub.2024.12.031.Peer-Reviewed Original ResearchConceptsMesolimbic dopamine systemConditioned stimulusDopamine systemNucleus accumbensDopamine functionDopamine releaseOccasion setterDopamine neuronsActivity of ventral tegmental area dopamine neuronsVentral tegmental area dopamine neuronsTheory of dopamine functionNon-overlapping presentationSucrose deliverySucrose rewardContextual cuesBehavioral outputAdaptive behaviorDynamic environmental contextBehavioral responsesFemale ratsAccumbensStimuliSeeking behaviorDopamineMotor controlPrefrontal 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 levelsMaleStressResponseSelective Mu-Opioid Receptor Imaging Using 18F‑Labeled Carfentanils
Lee S, Pearson T, Dhaynaut M, MacDonagh A, Wey H, Wilks M, Roth B, Hooker J, Normandin M. Selective Mu-Opioid Receptor Imaging Using 18F‑Labeled Carfentanils. Journal Of Medicinal Chemistry 2025, 68: 1632-1644. PMID: 39772615, DOI: 10.1021/acs.jmedchem.4c02287.Peer-Reviewed Original ResearchConceptsMu-opioid receptorsPositron emission tomographyIn vivo PET scansCarbon-11Neurobiological studiesCopper-mediated radiofluorinationMu-opioidReceptor imagingPET scansBrain uptakeFavorable pharmacokineticsImaging evaluationHigh molar activityMass doseEmission tomographyHalf-life of fluorine-18Synthetic opioidsFluorine-18Half-lifeIn vitro binding assaysBinding assaysClinical research useMolar activityCarfentanilResearch useL-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 ResearchConceptsN-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 recoveryPhosphorylationPainRepolarizationMinimal presynaptic protein machinery governing diverse kinetics of calcium-evoked neurotransmitter release
Bose D, Bera M, Norman C, Timofeeva Y, Volynski K, Krishnakumar S. Minimal presynaptic protein machinery governing diverse kinetics of calcium-evoked neurotransmitter release. Nature Communications 2024, 15: 10741. PMID: 39738049, PMCID: PMC11685451, DOI: 10.1038/s41467-024-54960-1.Peer-Reviewed Original ResearchConceptsSynaptotagmin-7Synaptotagmin-1Protein machinerySNARE complex assemblyFusion clampExocytosis processVesicle fusionVesicular fusionComplex assemblySynaptic vesiclesFusion assayMolecular basisPhysiologically relevant conditionsPresynaptic calcium influxNeurotransmitter releaseVesiclesSNAREProteinMachineryCompetitive bindingFusion dynamicsComplexinExocytosisFusionCalcium influxEfficacy 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 liabilityPeriodic ER-plasma membrane junctions support long-range Ca2+ signal integration in dendrites
Benedetti L, Fan R, Weigel A, Moore A, Houlihan P, Kittisopikul M, Park G, Petruncio A, Hubbard P, Pang S, Xu C, Hess H, Saalfeld S, Rangaraju V, Clapham D, De Camilli P, Ryan T, Lippincott-Schwartz J. Periodic ER-plasma membrane junctions support long-range Ca2+ signal integration in dendrites. Cell 2024, 188: 484-500.e22. PMID: 39708809, DOI: 10.1016/j.cell.2024.11.029.Peer-Reviewed Original ResearchConceptsEndoplasmic reticulum-plasma membrane junctionsEndoplasmic reticulum-plasma membranePlasma membrane of dendritesVoltage-gated Ca<sup>2+</sup> channelsER-plasma membrane junctionsMembrane of dendritesProtein kinase IIRyanodine receptorSynaptic inputsDendritic computationsSpine stimulationNeuronal dendritesKinase IIIntracellular signalingMembrane junctionsPlasma membraneER tubulesSignal propagationSignal transmissionSubcellular architectureRyanodineLadder-like arraysLocal activationReleaseDendritesNeuroinflammatory 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 ResearchConceptsResponse 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 spectrometryHierarchical gradients of multiple timescales in the mammalian forebrain
Song M, Shin E, Seo H, Soltani A, Steinmetz N, Lee D, Jung M, Paik S. Hierarchical gradients of multiple timescales in the mammalian forebrain. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2415695121. PMID: 39671181, PMCID: PMC11665873, DOI: 10.1073/pnas.2415695121.Peer-Reviewed Original ResearchConceptsTask-related activityHierarchical gradientIntrinsic timescalesFeatures of cortical circuitsCorrelations of neural activityCortex of monkeysTemporal correlation of neural activityBrain regionsAssociation areasNeural activitySpatial receptive fieldsBasal gangliaThalamic activityConnectivity patternsCortical circuitsHierarchical axisCortical projectionsMammalian brainTimescalesMammalian forebrainCortexBrainHierarchical organizationProperties of synapsesMultiple timescalesIntrathecal 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 blottingInterplay of Nav1.8 and Nav1.7 channels drives neuronal hyperexcitability in neuropathic pain
Vasylyev D, Zhao P, Schulman B, Waxman S. Interplay of Nav1.8 and Nav1.7 channels drives neuronal hyperexcitability in neuropathic pain. The Journal Of General Physiology 2024, 156: e202413596. PMID: 39378238, PMCID: PMC11465073, DOI: 10.1085/jgp.202413596.Peer-Reviewed Original ResearchConceptsDorsal root ganglionGain-of-function Nav1.7 mutationsDorsal root ganglion neuronsSodium channel Nav1.7Inherited erythromelalgiaNav1.7 mutationsNeuropathic painNeuronal hyperexcitabilityOpen-probabilityVoltage-gated sodium channel Nav1.7Hyperexcitability of DRG neuronsModel of neuropathic painSubthreshold membrane potential oscillationsResting membrane potentialMembrane potential oscillationsReduced firing probabilityIncreased rheobaseNav1.8 channelsDRG neuronsHuman genetic modelsNav1.8Root ganglionNav1.7 channelsNav1.7AP generationExperience of Euclidean geometry sculpts the development and dynamics of rodent hippocampal sequential cell assemblies
Farooq U, Dragoi G. Experience of Euclidean geometry sculpts the development and dynamics of rodent hippocampal sequential cell assemblies. Nature Communications 2024, 15: 8417. PMID: 39341810, PMCID: PMC11438871, DOI: 10.1038/s41467-024-52758-9.Peer-Reviewed Original ResearchProteomic 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 communication
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