2017
Loss of TrkB Signaling in Parvalbumin-Expressing Basket Cells Results in Network Activity Disruption and Abnormal Behavior
Xenos D, Kamceva M, Tomasi S, Cardin JA, Schwartz ML, Vaccarino FM. Loss of TrkB Signaling in Parvalbumin-Expressing Basket Cells Results in Network Activity Disruption and Abnormal Behavior. Cerebral Cortex 2017, 28: 3399-3413. PMID: 28968898, PMCID: PMC6132287, DOI: 10.1093/cercor/bhx173.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBehavior, AnimalCerebral CortexElectrophysiological PhenomenaEvoked PotentialsInterneuronsLearning DisabilitiesMembrane GlycoproteinsMemory DisordersMice, Inbred C57BLMice, KnockoutMovement DisordersNeocortexNeuronsParvalbuminsProtein-Tyrosine KinasesPyramidal CellsSurvival AnalysisConceptsBrain-derived neurotrophic factorCKO miceBasket cellsParvalbumin cellsExcitatory neuronsParvalbumin-expressing (PV-expressing) basket cellsPutative excitatory neuronsParvalbumin-Expressing InterneuronsPrincipal excitatory neuronsInhibitory synaptic connectionsCell-intrinsic roleCortical interneuron developmentConditional knockout miceTrkB receptorsMotor deficitsTrkB SignalingPyramidal neuronsGABAergic systemNeurotrophic factorLocal field potentialsProfound hyperactivityCortical volumeNeuronal activityKnockout miceSensory cortexMMP-2: A modulator of neuronal precursor activity and cognitive and motor behaviors
Li Q, Michaud M, Shankar R, Canosa S, Schwartz M, Madri JA. MMP-2: A modulator of neuronal precursor activity and cognitive and motor behaviors. Behavioural Brain Research 2017, 333: 74-82. PMID: 28666838, DOI: 10.1016/j.bbr.2017.06.041.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornCell MovementCell ProliferationCells, CulturedCognitionExploratory BehaviorGene Expression RegulationMatrix Metalloproteinase 2MiceMice, Inbred C57BLMice, KnockoutMotor ActivityNerve Tissue ProteinsNeural Stem CellsNeurogenesisOncogene Protein v-aktProliferating Cell Nuclear AntigenReceptors, CXCR4Spatial LearningConceptsNeural precursor cellsBroad substrate specificityNeurosphere formationAdherent neurospheresSecondary neurosphere formationNPC activitySubstrate specificityNPC numberCell surface moleculesZinc-containing enzymesAkt activationAbsence of MMP2Cell typesExtracellular matrixActivity assaysPrecursor cellsImportant roleNPC migrationMatrix metalloproteinase2Surface moleculesExpressionKO miceBioactive moleculesNestin expressionMMP2The role of endothelial HIF-1 αin the response to sublethal hypoxia in C57BL/6 mouse pups
Li Q, Michaud M, Park C, Huang Y, Couture R, Girodano F, Schwartz ML, Madri JA. The role of endothelial HIF-1 αin the response to sublethal hypoxia in C57BL/6 mouse pups. Laboratory Investigation 2017, 97: 356-369. PMID: 28092362, DOI: 10.1038/labinvest.2016.154.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornApoptosisBlotting, WesternCell HypoxiaCell ProliferationCells, CulturedDentate GyrusEndothelial CellsFemaleHypoxiaHypoxia-Inducible Factor 1, alpha SubunitLateral VentriclesMaleMice, Inbred C57BLMice, KnockoutMice, TransgenicMicroscopy, FluorescenceMotor ActivityNeural Stem CellsConceptsHIF-1 αBrain microvascular endothelial cellsNeuronal precursor cellsSubventricular zoneMicrovascular endothelial cellsOpen-field activityEndothelial cellsSublethal hypoxiaHIF-1 α expressionOpen-field activity testChronic sublethal hypoxiaEndothelial HIF-1Hypoxic conditionsC57BL/6 mouse pupsGender-specific differencesPremature birthC57BL/6 WTDentate gyrusHippocampal tissueDeficient miceΑ expressionMouse pupsMotor handicapParacrine effectsDentate gyrus tissue
2016
Mitochondria controlled by UCP2 determine hypoxia-induced synaptic remodeling in the cortex and hippocampus
Varela L, Schwartz ML, Horvath TL. Mitochondria controlled by UCP2 determine hypoxia-induced synaptic remodeling in the cortex and hippocampus. Neurobiology Of Disease 2016, 90: 68-74. PMID: 26777666, DOI: 10.1016/j.nbd.2016.01.004.Peer-Reviewed Original ResearchConceptsHippocampal neuronsMitochondria-endoplasmic reticulum interactionUCP2-KO miceEarly postnatal exposureLoss of synapsesOxygen tensionHigher brain regionsAdaptive mitochondrial responsesProtein 2 expressionHypothalamic circuitsPostnatal exposureKO miceSynaptic remodelingSystemic metabolismSynaptic inputsBrain cellsMetabolic controlNeuronal mitochondriaBrain regionsAdaptive responseNeuronsHippocampusMitochondrial dynamicsMetabolic challengesCortex
2015
Contribution of maternal oxygenic state to the effects of chronic postnatal hypoxia on mouse body and brain development
Salmaso N, Dominguez M, Kravitz J, Komitova M, Vaccarino FM, Schwartz ML. Contribution of maternal oxygenic state to the effects of chronic postnatal hypoxia on mouse body and brain development. Neuroscience Letters 2015, 604: 12-17. PMID: 26222256, PMCID: PMC4568169, DOI: 10.1016/j.neulet.2015.07.033.Peer-Reviewed Original ResearchConceptsBrain weightEffects of hypoxiaDam exposureCortical volumeBody weightHypoxic conditionsBrain developmentChronic postnatal hypoxiaLow birth weightPup body weightSame hypoxic conditionsChronic hypoxia exposureEarly postnatal pupsBody weight conditionsHypoxic mothersNeurological sequelaePostnatal hypoxiaPremature infantsHypoxic pupsBirth weightChronic hypoxiaHypoxic chamberHypoxic exposureLive birthsMouse modelModulation of Sox10, HIF-1α, Survivin, and YAP by Minocycline in the Treatment of Neurodevelopmental Handicaps following Hypoxic Insult
Li Q, Tsuneki M, Krauthammer M, Couture R, Schwartz M, Madri JA. Modulation of Sox10, HIF-1α, Survivin, and YAP by Minocycline in the Treatment of Neurodevelopmental Handicaps following Hypoxic Insult. American Journal Of Pathology 2015, 185: 2364-2378. PMID: 26209807, PMCID: PMC5801488, DOI: 10.1016/j.ajpath.2015.05.016.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsApoptosisCell Cycle ProteinsDisease Models, AnimalHypoxiaHypoxia-Inducible Factor 1, alpha SubunitInhibitor of Apoptosis ProteinsMice, Inbred C57BLMinocyclineMultiple SclerosisPhosphoproteinsRepressor ProteinsSOXE Transcription FactorsSurvivinUp-RegulationYAP-Signaling ProteinsConceptsMinocycline treatmentNeurodevelopmental handicapHypoxic insultEffects of minocyclineUntoward side effectsAnimal model studiesPotential therapeutic targetSublethal hypoxic conditionsPremature infantsMultiple sclerosisCurrent therapiesTreatment trialsChronic hypoxiaSynaptic transmissionMurine modelMouse pupsMotor handicapNewborn populationSide effectsTherapeutic targetSublethal hypoxiaHIF-1αNerve transmissionMinocyclineCognitive function
2013
Hypoxia-Induced Developmental Delays of Inhibitory Interneurons Are Reversed by Environmental Enrichment in the Postnatal Mouse Forebrain
Komitova M, Xenos D, Salmaso N, Tran KM, Brand T, Schwartz ML, Ment L, Vaccarino FM. Hypoxia-Induced Developmental Delays of Inhibitory Interneurons Are Reversed by Environmental Enrichment in the Postnatal Mouse Forebrain. Journal Of Neuroscience 2013, 33: 13375-13387. PMID: 23946395, PMCID: PMC3742925, DOI: 10.1523/jneurosci.5286-12.2013.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Adhesion Molecules, NeuronalCerebral CortexChromatography, High Pressure LiquidDisease Models, AnimalExtracellular Matrix ProteinsGene Knock-In TechniquesHousing, AnimalHypoxiaImmunohistochemistryInterneuronsMiceMice, Inbred C57BLMice, TransgenicNerve Tissue ProteinsParvalbuminsProsencephalonReelin ProteinSerine EndopeptidasesSomatostatinConceptsCortical interneuronsNormoxic controlsMarker expressionPostnatal cortical developmentVasoactive intestinal peptidePostnatal day 3Central nervous systemTotal GABA contentImpact of hypoxicPostnatal mouse forebrainEnvironmental enrichmentIntestinal peptideGABAergic interneuronsFrontal neocortexInhibitory interneuronsCortical developmentMouse modelReelin expressionInterneuron numbersNervous systemDay 3Cognitive impairmentInterneuronsHousing miceRLN expression
2012
Environmental Enrichment Increases the GFAP+ Stem Cell Pool and Reverses Hypoxia-Induced Cognitive Deficits in Juvenile Mice
Salmaso N, Silbereis J, Komitova M, Mitchell P, Chapman K, Ment LR, Schwartz ML, Vaccarino FM. Environmental Enrichment Increases the GFAP+ Stem Cell Pool and Reverses Hypoxia-Induced Cognitive Deficits in Juvenile Mice. Journal Of Neuroscience 2012, 32: 8930-8939. PMID: 22745493, PMCID: PMC3399175, DOI: 10.1523/jneurosci.1398-12.2012.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceAnimalsAnimals, NewbornBromodeoxyuridineCell CountCell DifferentiationCognition DisordersDeoxyuridineDisease Models, AnimalEnvironmentEstrogen AntagonistsFemaleGene Expression Regulation, DevelopmentalGlial Fibrillary Acidic ProteinGreen Fluorescent ProteinsHumansHypoxiaIdoxuridineKi-67 AntigenMaleMaze LearningMiceMice, Inbred C57BLMice, TransgenicNerve Tissue ProteinsNeurogenesisNeurogliaReceptors, EstrogenStem CellsTamoxifenConceptsHypoxic injuryBrain injuryAstroglial cellsChronic hypoxic injuryDevelopmental brain injuryLow birth weightCell poolEnvironmental enrichmentAdult brain injuryAbnormal lung developmentStem cell poolPerinatal hypoxic injuryFate-mapping modelsSocio-demographic factorsNeurobiological recoveryHippocampal neurogenesisVLBW cohortPremature childrenBirth weightCardiovascular abnormalitiesJuvenile miceAnimal modelsLung developmentInjuryCognitive deficits
2009
Strain Differences in Behavioral and Cellular Responses to Perinatal Hypoxia and Relationships to Neural Stem Cell Survival and Self-Renewal Modeling the Neurovascular Niche
Li Q, Liu J, Michaud M, Schwartz ML, Madri JA. Strain Differences in Behavioral and Cellular Responses to Perinatal Hypoxia and Relationships to Neural Stem Cell Survival and Self-Renewal Modeling the Neurovascular Niche. American Journal Of Pathology 2009, 175: 2133-2145. PMID: 19815710, PMCID: PMC2774076, DOI: 10.2353/ajpath.2009.090354.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBehavior, AnimalCell DifferentiationCell MovementCell SurvivalCells, CulturedChemokine CXCL12Endothelial CellsEnzyme ActivationFemaleHumansHypoxiaHypoxia-Inducible Factor 1, alpha SubunitHypoxia-Inducible Factor-Proline DioxygenasesInfantInfant, NewbornInfant, PrematureMaleMiceMice, Inbred C57BLMice, Inbred StrainsNeuronsNeuropsychological TestsPhosphatidylinositol 3-KinasesProcollagen-Proline DioxygenaseProto-Oncogene Proteins c-aktSignal TransductionStem CellsConceptsChronic hypoxiaC57 miceHIF-1alphaLow birth weight infant populationMatrix metalloproteinase-9 activityStromal-derived factor-1CD-1 miceMetalloproteinase-9 activityAdult C57 miceHypoxia-induced factorNeural stem cell survivalHigher apoptosis ratePerinatal hypoxiaRepair/recoveryClinical improvementNeurodevelopmental handicapPreventive therapyPremature infantsNeurogenic zonesNeurovascular nicheInfant populationC57BL/6 pupsProlyl hydroxylase domain 2Migratory responsivenessStem cell survivalHypoxic Injury during Neonatal Development in Murine Brain: Correlation between In Vivo DTI Findings and Behavioral Assessment
Chahboune H, Ment LR, Stewart WB, Rothman DL, Vaccarino FM, Hyder F, Schwartz ML. Hypoxic Injury during Neonatal Development in Murine Brain: Correlation between In Vivo DTI Findings and Behavioral Assessment. Cerebral Cortex 2009, 19: 2891-2901. PMID: 19380380, PMCID: PMC2774398, DOI: 10.1093/cercor/bhp068.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornBehavior, AnimalBrainDiffusion Magnetic Resonance ImagingHypoxia, BrainMaleMiceMice, Inbred C57BLStatistics as TopicConceptsChronic sublethal hypoxiaLow birth weight preterm infantsBirth weight preterm infantsHypoxia-induced modificationNeonatal rodent modelPreterm birth resultsWeight preterm infantsSignificant neurodevelopmental disabilitiesOpen field taskGreater locomotor activityPreterm infantsPreterm birthNeurodevelopmental consequencesBirth resultsHypoxic injurySomatosensory cortexCaudate putamenCallosal connectivityCorpus callosumBehavioral deficitsNeurodevelopmental disabilitiesRodent modelsNeonatal developmentDTI findingsSublethal hypoxia
2007
Modeling the neurovascular niche: Murine strain differences mimic the range of responses to chronic hypoxia in the premature newborn
Li Q, Michaud M, Stewart W, Schwartz M, Madri JA. Modeling the neurovascular niche: Murine strain differences mimic the range of responses to chronic hypoxia in the premature newborn. Journal Of Neuroscience Research 2007, 86: 1227-1242. PMID: 18092360, PMCID: PMC2644407, DOI: 10.1002/jnr.21597.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornApoptosisBlotting, WesternBrainCell ProliferationDisease Models, AnimalGene ExpressionHematopoiesis, ExtramedullaryHumansHypoxia, BrainImmunohistochemistryImmunoprecipitationInfant, NewbornInfant, PrematureIntercellular Signaling Peptides and ProteinsMiceMice, Inbred C57BLNitric OxideStem CellsConceptsNeural progenitor cellsChronic hypoxiaSubventricular zonePreterm birth resultsLow baseline levelsHypoxia-induced levelsNeurogenic responseNeurovascular nicheHypoxic insultBlunted responseBirth resultsC57BL/6 pupsBaseline levelsMotor disabilityMouse strainsGrowth factorVariable recoveryHypoxiaProgenitor cellsPupsRecent evidenceSignificant cognitiveHypoxicApoptotic responseResponse
2004
Neonatal hypoxia suppresses oligodendrocyte Nogo-A and increases axonal sprouting in a rodent model for human prematurity
Weiss J, Takizawa B, McGee A, Stewart WB, Zhang H, Ment L, Schwartz M, Strittmatter S. Neonatal hypoxia suppresses oligodendrocyte Nogo-A and increases axonal sprouting in a rodent model for human prematurity. Experimental Neurology 2004, 189: 141-149. PMID: 15296844, DOI: 10.1016/j.expneurol.2004.05.018.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAnimalsAnimals, NewbornAxonsBehavior, AnimalBiotinCentral Nervous SystemDextransDisease Models, AnimalExploratory BehaviorHumansHypoxia, BrainImmunoblottingImmunohistochemistryInfant, NewbornInfant, PrematureMiceMice, Inbred C57BLMyelin Basic ProteinMyelin ProteinsMyelin-Associated GlycoproteinNogo ProteinsOligodendrogliaReceptors, Cell SurfaceTime FactorsConceptsChronic sublethal hypoxiaPeriventricular leukomalaciaMyelin associated glycoproteinCorticospinal tractWhite matterLow birth weight infantsCerebral white matter volumeBirth weight infantsLow birth weightAnterograde axonal tracingPeriventricular white matterPremature human infantsCNS white matterWhite matter volumeHypoxia-induced reductionWeight infantsAxonal sproutingCerebral ventriculomegalyCorticofugal fibersLocomotor hyperactivityNeonatal hypoxiaPersistent abnormalitiesMotor cortexBirth weightHuman prematurity