2024
Transient impairment in microglial function causes sex-specific deficits in synaptic maturity and hippocampal function in mice exposed to early adversity
Ahmed S, Polis B, Jamwal S, Sanganahalli B, MacDowell Kaswan Z, Islam R, Kim D, Bowers C, Giuliano L, Biederer T, Hyder F, Kaffman A. Transient impairment in microglial function causes sex-specific deficits in synaptic maturity and hippocampal function in mice exposed to early adversity. Brain Behavior And Immunity 2024, 122: 95-109. PMID: 39134183, PMCID: PMC11402597, DOI: 10.1016/j.bbi.2024.08.010.Peer-Reviewed Original ResearchEarly-life adversityModel of early-life adversityContextual fear conditioningLimited beddingFear conditioningSynaptic engulfmentLB miceSynaptic pruningSex-specific deficitsHippocampus of maleSex-specific effectsHippocampal deficitsAdolescent miceHippocampal functionEarly adversityChemogenetic activationSynaptic connectionsBehavioral aberrationsPotential compensatory mechanismsSynaptic abnormalitiesHippocampusAblation of microgliaRodent hippocampusDeficitsWeeks of lifeMicroglia: The Drunken Gardeners of Early Adversity
Ahmed S, Polis B, Kaffman A. Microglia: The Drunken Gardeners of Early Adversity. Biomolecules 2024, 14: 964. PMID: 39199352, PMCID: PMC11353196, DOI: 10.3390/biom14080964.Peer-Reviewed Original ResearchEarly life adversityAbnormal immune responseImpact of early life adversityHistory of early life adversityRodent studiesImmune responseNegative childhood experiencesConditions in adulthoodLevels of inflammatory cytokinesLong-term alterationsRefractory responses to treatmentAbnormal brain developmentMicroglial functionResponse to treatmentTraumatic brain injuryResident immune cellsStress reactivityEarly adversityLife adversitySubstance useChildhood experiencesMicroglial inflammatory responseImmune cellsIn adulthoodPeriod of developmentEarly adversity causes sex-specific deficits in perforant pathway connectivity and contextual memory in adolescent mice
Islam R, White J, Arefin T, Mehta S, Liu X, Polis B, Giuliano L, Ahmed S, Bowers C, Zhang J, Kaffman A. Early adversity causes sex-specific deficits in perforant pathway connectivity and contextual memory in adolescent mice. Biology Of Sex Differences 2024, 15: 39. PMID: 38715106, PMCID: PMC11075329, DOI: 10.1186/s13293-024-00616-0.Peer-Reviewed Original ResearchConceptsLateral entorhinal cortexContextual fear conditioningDorsal hippocampusHippocampal developmentSex differencesFear conditioningEarly adversityLimited beddingSevere deficitsModel of early adversitySex-specific deficitsReelin-positive neuronsPerforant pathwayReelin-positive cellsDiffusion magnetic resonance imagingEx vivo diffusion magnetic resonance imagingContextual freezingContextual memoryAdolescent miceHippocampal functionLife adversityEntorhinal cortexHippocampusDeficitsAdolescent males
2023
EARLY ADVERSITY CAUSES SEX-SPECIFIC DEFICITS IN ENTORHINAL-DORSAL HIPPOCAMPUS CONNECTIVITY AND CONTEXTUAL FEAR CONDITIONING IN ADOLESCENT MICE
Islam R, Arefin T, White J, Polis B, Ahmed S, Liu X, Zhang J, Kaffman A. EARLY ADVERSITY CAUSES SEX-SPECIFIC DEFICITS IN ENTORHINAL-DORSAL HIPPOCAMPUS CONNECTIVITY AND CONTEXTUAL FEAR CONDITIONING IN ADOLESCENT MICE. IBRO Neuroscience Reports 2023, 15: s103-s104. DOI: 10.1016/j.ibneur.2023.08.089.Peer-Reviewed Original ResearchEarly adversity changes the economic conditions of mouse structural brain network organization
Carozza S, Holmes J, Vértes P, Bullmore E, Arefin T, Pugliese A, Zhang J, Kaffman A, Akarca D, Astle D. Early adversity changes the economic conditions of mouse structural brain network organization. Developmental Psychobiology 2023, 65: e22405. PMID: 37607894, PMCID: PMC10505050, DOI: 10.1002/dev.22405.Peer-Reviewed Original ResearchConceptsEarly adversityStructural brain network organizationPostnatal stressBrain network organizationMental health outcomesEarly life adversityCognitive abilitiesNeural processesLife adversityConnectome organizationAdversityStructural connectomeConnectomeNetwork organizationGenerative processMouse connectomeHealth outcomesLong-distance connectionsOrganizationEffective responseAdaptive mechanismsAbilityStressWiring cost
2022
Early life stress impairs synaptic pruning in the developing hippocampus
Dayananda KK, Ahmed S, Wang D, Polis B, Islam R, Kaffman A. Early life stress impairs synaptic pruning in the developing hippocampus. Brain Behavior And Immunity 2022, 107: 16-31. PMID: 36174883, PMCID: PMC10497209, DOI: 10.1016/j.bbi.2022.09.014.Peer-Reviewed Original ResearchConceptsSynaptic pruningMicroglial ramificationHippocampal functionAbnormal hippocampal functionCA1 pyramidal neuronsExpression of TREM2Increased spine densityRamification of microgliaEarly life adversityNormal hippocampal functionSynaptic engulfmentClinical outcomesPyramidal neuronsSpine densityFemale miceHippocampal stimulationSevere formHippocampal developmentPhagocytic activitySevere impairmentEx vivoLife adversityThird weekEarly adversityMice
2021
Macroscopic Structural and Connectome Mapping of the Mouse Brain Using Diffusion Magnetic Resonance Imaging
Arefin TM, Lee CH, White JD, Zhang J, Kaffman A. Macroscopic Structural and Connectome Mapping of the Mouse Brain Using Diffusion Magnetic Resonance Imaging. Bio-protocol 2021, 11: e4221. PMID: 34909442, PMCID: PMC8635841, DOI: 10.21769/bioprotoc.4221.Peer-Reviewed Original ResearchEarly life stressMagnetic resonance imagingMouse brainDiffusion magnetic resonance imagingMouse modelResonance imagingWhole-brain voxel-based analysisVoxel-based analysisClinical trialsPostnatal stressPreclinical studiesNeurological conditionsAdult miceEntire mouse brainStructural abnormalitiesBrain regionsMouse strainsBrain connectivityBrainLife stressTranslational utilityStructural connectivityRodentsMiceTranslational workEditorial: Effects of Early Life Stress on Neurodevelopment and Health: Bridging the Gap Between Human Clinical Studies and Animal Models
Kaffman A, Herringa RJ, Sanchez MM. Editorial: Effects of Early Life Stress on Neurodevelopment and Health: Bridging the Gap Between Human Clinical Studies and Animal Models. Frontiers In Human Neuroscience 2021, 15: 751102. PMID: 34675791, PMCID: PMC8523778, DOI: 10.3389/fnhum.2021.751102.Peer-Reviewed Original ResearchDeficits in hippocampal-dependent memory across different rodent models of early life stress: systematic review and meta-analysis
Rocha M, Wang D, Avila-Quintero V, Bloch MH, Kaffman A. Deficits in hippocampal-dependent memory across different rodent models of early life stress: systematic review and meta-analysis. Translational Psychiatry 2021, 11: 231. PMID: 33879774, PMCID: PMC8058062, DOI: 10.1038/s41398-021-01352-4.Peer-Reviewed Original ResearchConceptsEarly life stressNovel object recognitionMorris water mazeDifferent rodent modelsContextual fear conditioningMaternal separationHippocampal-dependent memoryVentral hippocampusDorsal hippocampusRodent modelsLife stressAbnormal hippocampal developmentStandardized mean differenceSimilar cognitive deficitsWeb of ScienceModerate effect sizeCFC taskFunctional deficitsFear conditioningInclusion criteriaPreclinical studiesReduced freezingHippocampal developmentLimited beddingWater mazeWhite-Matter Repair as a Novel Therapeutic Target for Early Adversity
Islam R, Kaffman A. White-Matter Repair as a Novel Therapeutic Target for Early Adversity. Frontiers In Neuroscience 2021, 15: 657693. PMID: 33897364, PMCID: PMC8062784, DOI: 10.3389/fnins.2021.657693.Peer-Reviewed Original ResearchMyelin developmentWhite matter repairNovel therapeutic targetPre-clinical workNovel therapeutic interventionsNon-human primatesNew agentsTherapeutic targetAnimal modelsTherapeutic interventionsTranslational researchEarly adversityRecent mechanistic studiesMolecular mechanismsRodentsDiverse mammalian species
2020
The Promise of Automated Home-Cage Monitoring in Improving Translational Utility of Psychiatric Research in Rodents
Mingrone A, Kaffman A, Kaffman A. The Promise of Automated Home-Cage Monitoring in Improving Translational Utility of Psychiatric Research in Rodents. Frontiers In Neuroscience 2020, 14: 618593. PMID: 33390898, PMCID: PMC7773806, DOI: 10.3389/fnins.2020.618593.Peer-Reviewed Original ResearchEarly life stress causes sex-specific changes in adult fronto-limbic connectivity that differentially drive learning
White JD, Arefin TM, Pugliese A, Lee CH, Gassen J, Zhang J, Kaffman A. Early life stress causes sex-specific changes in adult fronto-limbic connectivity that differentially drive learning. ELife 2020, 9: e58301. PMID: 33259286, PMCID: PMC7725504, DOI: 10.7554/elife.58301.Peer-Reviewed Original ResearchConceptsEarly life stressSex-specific changesContextual freezing behaviorFronto-limbic connectivityLife stressHigh-resolution diffusion magnetic resonance imagingSex-specific mechanismsMagnetic resonance imagingNeuroanatomical alterationsPostnatal stressDiffusion magnetic resonance imagingMouse modelFronto-limbicResonance imagingModerate responseMalesTranslational workFemalesRodentsFreezing behaviorHuman imagingImagingHypoconnectivityInjurySystematic review and meta-analysis: effects of maternal separation on anxiety-like behavior in rodents
Wang D, Levine JLS, Avila-Quintero V, Bloch M, Kaffman A. Systematic review and meta-analysis: effects of maternal separation on anxiety-like behavior in rodents. Translational Psychiatry 2020, 10: 174. PMID: 32483128, PMCID: PMC7264128, DOI: 10.1038/s41398-020-0856-0.Peer-Reviewed Original ResearchConceptsOpen field testEarly life stressSystematic reviewEffects of MSEffects of ELSAnxiety-like behaviorDefensive behaviorAnxiogenic effectsMaternal separationRodent modelsRatsEarly adversityMiceAbility of MSLife stressLack of standardizationChildhood maltreatmentRodentsExploratory behaviorEffect sizeInconsistent resultsELS modelImportant differencesReviewMS protocol
2019
Editorial Perspective: Childhood maltreatment – the problematic unisex assumption
White JD, Kaffman A. Editorial Perspective: Childhood maltreatment – the problematic unisex assumption. Journal Of Child Psychology And Psychiatry 2019, 61: 732-734. PMID: 31828779, PMCID: PMC7242136, DOI: 10.1111/jcpp.13177.Peer-Reviewed Original ResearchThe Moderating Effects of Sex on Consequences of Childhood Maltreatment: From Clinical Studies to Animal Models
White JD, Kaffman A. The Moderating Effects of Sex on Consequences of Childhood Maltreatment: From Clinical Studies to Animal Models. Frontiers In Neuroscience 2019, 13: 1082. PMID: 31680821, PMCID: PMC6797834, DOI: 10.3389/fnins.2019.01082.Peer-Reviewed Original ResearchEnhancing the Utility of Preclinical Research in Neuropsychiatry Drug Development
Kaffman A, White JD, Wei L, Johnson FK, Krystal JH. Enhancing the Utility of Preclinical Research in Neuropsychiatry Drug Development. Methods In Molecular Biology 2019, 2011: 3-22. PMID: 31273690, PMCID: PMC6895673, DOI: 10.1007/978-1-4939-9554-7_1.Peer-Reviewed Original ResearchConceptsPreclinical researchAnimal modelsPsychiatric conditionsLower clinical success ratesClinical success rateCommon psychiatric conditionsPsychiatric clinical trialsClinical trialsNew pharmacotherapiesMore effective interventionsPreclinical workPsychiatric disordersPsychiatric pathophysiologyMental illnessSystematic reviewEffective interventionsAnimal experimentsDrug development processSuccess rateDrug developmentHuman psychopathologyPharmaceutical companiesPredictive validityLarge pharmaceutical companiesAnimals
2018
Amygdala hyper-connectivity in a mouse model of unpredictable early life stress
Johnson FK, Delpech JC, Thompson GJ, Wei L, Hao J, Herman P, Hyder F, Kaffman A. Amygdala hyper-connectivity in a mouse model of unpredictable early life stress. Translational Psychiatry 2018, 8: 49. PMID: 29463821, PMCID: PMC5820270, DOI: 10.1038/s41398-018-0092-z.Peer-Reviewed Original ResearchConceptsEarly life stressAdult male miceAnxiety-like behaviorLimited beddingMale miceMouse modelUnpredictable early life stressAmygdala-prefrontal cortex connectivityChildhood maltreatmentOpen field testFrontolimbic brain regionsResting-state fMRIFrontolimbic connectivityPostnatal stressCortex connectivityAbnormal connectivityAmygdala connectivityAdult miceAnimal modelsFrontolimbic circuitsBrain regionsStress paradigmPrefrontal cortexRobust increaseMice
2017
Early life stress perturbs the function of microglia in the developing rodent brain: New insights and future challenges
Johnson FK, Kaffman A. Early life stress perturbs the function of microglia in the developing rodent brain: New insights and future challenges. Brain Behavior And Immunity 2017, 69: 18-27. PMID: 28625767, PMCID: PMC5732099, DOI: 10.1016/j.bbi.2017.06.008.Peer-Reviewed Original ResearchConceptsEarly life stressMicroglial functionLife stressAnimal modelsBehavioral abnormalitiesStress-induced neuroinflammationMicroglial cell numberFunction of microgliaMicroglial gene expressionChildhood maltreatmentInnate immune systemMedical complicationsLong-term adultAbnormal maturationMouse modelSynaptic pruningRodent brainImmune systemPhagocytic activityAxonal growthBrain developmentDaily separationFirst weekGene expressionAbnormalities
2016
Early life stress perturbs the maturation of microglia in the developing hippocampus
Delpech JC, Wei L, Hao J, Yu X, Madore C, Butovsky O, Kaffman A. Early life stress perturbs the maturation of microglia in the developing hippocampus. Brain Behavior And Immunity 2016, 57: 79-93. PMID: 27301858, PMCID: PMC5010940, DOI: 10.1016/j.bbi.2016.06.006.Peer-Reviewed Original ResearchConceptsEarly life stressHippocampal developmentLife stressPhagocytic activityAbnormal hippocampal developmentNormal hippocampal developmentMorphology of microgliaPostnatal day 28Vivo phagocytic activityImpairs hippocampal functionMaturation of microgliaImmune panelHippocampal microgliaMicroglial activityMicroglial functionNormal cell numbersSynaptic maturationOld miceMicrogliaMouse modelRodent modelsSynaptic pruningDay 28Old pupsHippocampus
2015
Early-Life Stress Perturbs Key Cellular Programs in the Developing Mouse Hippocampus
Wei L, Hao J, Lacher RK, Abbott T, Chung L, Colangelo CM, Kaffman A. Early-Life Stress Perturbs Key Cellular Programs in the Developing Mouse Hippocampus. Developmental Neuroscience 2015, 37: 476-488. PMID: 26068561, PMCID: PMC4644446, DOI: 10.1159/000430861.Peer-Reviewed Original ResearchConceptsEarly life stressEffects of ELSHippocampal developmentSynaptic maturationAxonal growthExpression of proteinsJuvenile hippocampusJuvenile miceHippocampal functionAbnormal hippocampal developmentNormal axonal growthHippocampal-dependent memoryNormal synaptic developmentHuman imaging studiesTotal protein contentCA1 neuronsSynaptic markersFemale miceMouse modelMouse hippocampusSynaptic pruningAnimal modeMature spinesHippocampusSynaptic proteins