2022
LINE-1 activation in the cerebellum drives ataxia
Takahashi T, Stoiljkovic M, Song E, Gao XB, Yasumoto Y, Kudo E, Carvalho F, Kong Y, Park A, Shanabrough M, Szigeti-Buck K, Liu ZW, Kristant A, Zhang Y, Sulkowski P, Glazer PM, Kaczmarek LK, Horvath TL, Iwasaki A. LINE-1 activation in the cerebellum drives ataxia. Neuron 2022, 110: 3278-3287.e8. PMID: 36070749, PMCID: PMC9588660, DOI: 10.1016/j.neuron.2022.08.011.Peer-Reviewed Original ResearchConceptsLINE-1 activationL1 activationAtaxia telangiectasia patientsNuclear element-1Transposable elementsEpigenetic silencersHuman genomeL1 promoterMolecular regulatorsDNA damagePurkinje cell dysfunctionElement 1First direct evidenceTelangiectasia patientsDirect targetingCerebellar expressionNeurodegenerative diseasesDisease etiologyCalcium homeostasis
2021
Ketogenic diet restrains aging-induced exacerbation of coronavirus infection in mice
Ryu S, Shchukina I, Youm YH, Qing H, Hilliard B, Dlugos T, Zhang X, Yasumoto Y, Booth CJ, Fernández-Hernando C, Suárez Y, Khanna K, Horvath TL, Dietrich MO, Artyomov M, Wang A, Dixit VD. Ketogenic diet restrains aging-induced exacerbation of coronavirus infection in mice. ELife 2021, 10: e66522. PMID: 34151773, PMCID: PMC8245129, DOI: 10.7554/elife.66522.Peer-Reviewed Original ResearchConceptsΓδ T cellsKetogenic dietCoronavirus infectionAged miceT cellsHigher systemic inflammationInfected aged miceCOVID-19 severityCOVID-19 infectionActivation of ketogenesisMouse hepatitis virus strain A59Systemic inflammationInflammatory damageInfluenza infectionClinical hallmarkNLRP3 inflammasomeImmune surveillanceAdipose tissuePotential treatmentInfectionMiceStrongest predictorLungMortalityAgeUcp2-dependent microglia-neuronal coupling controls ventral hippocampal circuit function and anxiety-like behavior
Yasumoto Y, Stoiljkovic M, Kim JD, Sestan-Pesa M, Gao XB, Diano S, Horvath TL. Ucp2-dependent microglia-neuronal coupling controls ventral hippocampal circuit function and anxiety-like behavior. Molecular Psychiatry 2021, 26: 2740-2752. PMID: 33879866, PMCID: PMC8056795, DOI: 10.1038/s41380-021-01105-1.Peer-Reviewed Original ResearchConceptsAnxiety-like behaviorReactive oxygen speciesMicroglia-synapse contactsSpine synapse numberHippocampal circuit functionNeuronal circuit dysfunctionMicroglial productionVentral hippocampusCircuit dysfunctionSpine synapsesSynapse numberAdult brainTransient riseMitochondrial ROS generationMicrogliaBrain functionConditional ablationPhagocytic inclusionsSynaptic elementsProtein 2ROS generationSignificant reductionCircuit functionConsequent accumulationOxygen speciesDiscovery and functional interrogation of SARS-CoV-2 RNA-host protein interactions
Flynn RA, Belk JA, Qi Y, Yasumoto Y, Wei J, Alfajaro MM, Shi Q, Mumbach MR, Limaye A, DeWeirdt PC, Schmitz CO, Parker KR, Woo E, Chang HY, Horvath TL, Carette JE, Bertozzi CR, Wilen CB, Satpathy AT. Discovery and functional interrogation of SARS-CoV-2 RNA-host protein interactions. Cell 2021, 184: 2394-2411.e16. PMID: 33743211, PMCID: PMC7951565, DOI: 10.1016/j.cell.2021.03.012.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 RNASARS-CoV-2Virus-induced cell deathHost protein interactionsRNA-binding proteinActive infectionRNA virusesHost-virus interfaceGlobal mortalityTherapeutic benefitCRISPR screensAntiviral factorsProtein interactionsAntiviral activityViral specificityHost pathwaysFunctional RNA-binding proteinsFunctional connectionsRNA-centric approachesCell deathHost proteinsVirusFunctional interrogationRNAComprehensive catalogNeuroinvasion of SARS-CoV-2 in human and mouse brain
Song E, Zhang C, Israelow B, Lu-Culligan A, Prado AV, Skriabine S, Lu P, Weizman OE, Liu F, Dai Y, Szigeti-Buck K, Yasumoto Y, Wang G, Castaldi C, Heltke J, Ng E, Wheeler J, Alfajaro MM, Levavasseur E, Fontes B, Ravindra NG, Van Dijk D, Mane S, Gunel M, Ring A, Kazmi SAJ, Zhang K, Wilen CB, Horvath TL, Plu I, Haik S, Thomas JL, Louvi A, Farhadian SF, Huttner A, Seilhean D, Renier N, Bilguvar K, Iwasaki A. Neuroinvasion of SARS-CoV-2 in human and mouse brain. Journal Of Experimental Medicine 2021, 218: e20202135. PMID: 33433624, PMCID: PMC7808299, DOI: 10.1084/jem.20202135.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Central nervous systemSARS-CoV-2 neuroinvasionImmune cell infiltratesCOVID-19 patientsType I interferon responseMultiple organ systemsCOVID-19I interferon responseHuman brain organoidsNeuroinvasive capacityCNS infectionsCell infiltrateNeuronal infectionPathological featuresCortical neuronsRespiratory diseaseDirect infectionCerebrospinal fluidNervous systemMouse brainInterferon responseOrgan systemsHuman ACE2Infection
2020
Crosstalk between maternal perinatal obesity and offspring dopaminergic circuitry
Yasumoto Y, Horvath TL. Crosstalk between maternal perinatal obesity and offspring dopaminergic circuitry. Journal Of Clinical Investigation 2020, 130: 3416-3418. PMID: 32510474, PMCID: PMC7324168, DOI: 10.1172/jci138123.Peer-Reviewed Original ResearchConceptsMedium spiny neuronsHigh-fat dietMaternal obesityD1 medium spiny neuronsD2 medium spiny neuronsFetal brain developmentDopamine midbrain neuronsBehavioral phenotypesAltered excitatoryPerinatal obesityMaternal miceInhibitory balanceSpiny neuronsDopaminergic circuitryMidbrain neuronsBrain developmentObesityAdult HealthOffspring developmentNeuronsPhenotypeExcitatoryMice
2019
The role of fatty acid binding protein 7 in spinal cord astrocytes in a mouse model of experimental autoimmune encephalomyelitis
Kamizato K, Sato S, Shil SK, Umaru BA, Kagawa Y, Yamamoto Y, Ogata M, Yasumoto Y, Okuyama Y, Ishii N, Owada Y, Miyazaki H. The role of fatty acid binding protein 7 in spinal cord astrocytes in a mouse model of experimental autoimmune encephalomyelitis. Neuroscience 2019, 409: 120-129. PMID: 31051217, DOI: 10.1016/j.neuroscience.2019.03.050.Peer-Reviewed Original ResearchConceptsExperimental autoimmune encephalomyelitisSpinal cordAutoimmune encephalomyelitisMultiple sclerosisWT miceMouse modelFabp7 KO miceSpinal cord astrocytesLumbar spinal cordInduction of inflammationWild-type miceCentral nervous systemProtein 7Role of FABP7Fatty acid homeostasisMRNA expression levelsLate phaseEAE onsetEAE symptomsAstrocyte activationClinical scoresFatty acidsInflammatory cytokinesMyelin degenerationType miceFABP7 Protects Astrocytes Against ROS Toxicity via Lipid Droplet Formation
Islam A, Kagawa Y, Miyazaki H, Shil SK, Umaru BA, Yasumoto Y, Yamamoto Y, Owada Y. FABP7 Protects Astrocytes Against ROS Toxicity via Lipid Droplet Formation. Molecular Neurobiology 2019, 56: 5763-5779. PMID: 30680690, DOI: 10.1007/s12035-019-1489-2.Peer-Reviewed Original ResearchConceptsMitogen-activated protein kinaseROS toxicityLipid droplet formationLD accumulationPeroxiredoxin 1Stress-activated protein kinase/c-Jun N-terminal kinaseProtein kinase/c-Jun N-terminal kinaseP38 mitogen-activated protein kinaseC-Jun N-terminal kinaseReactive oxygen species stressRole of FABP7ROS inductionU87 human glioma cell lineN-terminal kinaseOxygen species stressActivation of apoptosisFABP7 overexpressionProtein bindsProtein kinaseLD formationLong-chain fatty acidsROS stressHuman glioma cell linesLipid dynamicsWild-type astrocytes
2018
FABP3 in the Anterior Cingulate Cortex Modulates the Methylation Status of the Glutamic Acid Decarboxylase67 Promoter Region
Yamamoto Y, Kida H, Kagawa Y, Yasumoto Y, Miyazaki H, Islam A, Ogata M, Yanagawa Y, Mitsushima D, Fukunaga K, Owada Y. FABP3 in the Anterior Cingulate Cortex Modulates the Methylation Status of the Glutamic Acid Decarboxylase67 Promoter Region. Journal Of Neuroscience 2018, 38: 10411-10423. PMID: 30341178, PMCID: PMC6596254, DOI: 10.1523/jneurosci.1285-18.2018.Peer-Reviewed Original ResearchConceptsAnterior cingulate cortexHistone deacetylase 1KO miceCellular chaperonesFatty acid-binding proteinMethionine administrationTranscriptional repressor complexMouse anterior cingulate cortexGlutamic acid decarboxylase 67Promoter methylationEnzyme glutamic acid decarboxylase 67Emotional behaviorKO male miceGABAergic inhibitory interneuronsRepressor complexTranscriptional regulationSignal transductionAcid-binding proteinDNA methylationGene transcriptionMethyl-CpGIntracellular traffickingPromoter regionHuman psychiatric disordersPUFA homeostasisGlial Fatty Acid-Binding Protein 7 (FABP7) Regulates Neuronal Leptin Sensitivity in the Hypothalamic Arcuate Nucleus
Yasumoto Y, Miyazaki H, Ogata M, Kagawa Y, Yamamoto Y, Islam A, Yamada T, Katagiri H, Owada Y. Glial Fatty Acid-Binding Protein 7 (FABP7) Regulates Neuronal Leptin Sensitivity in the Hypothalamic Arcuate Nucleus. Molecular Neurobiology 2018, 55: 9016-9028. PMID: 29623545, DOI: 10.1007/s12035-018-1033-9.Peer-Reviewed Original ResearchConceptsFabp7 KO miceFatty Acid Binding Protein 7Arcuate nucleusHypothalamic arcuate nucleusKO miceFood intakeMedian eminenceFatty acid-binding protein 7Energy homeostasisWeight gainSingle leptin injectionHigh-fat dietNon-neuronal cell typesWild-type miceProtein 7Systemic energy homeostasisLeptin-induced activationPrimary astrocyte culturesNeuronal leptinHypothalamic astrocytesWT miceLeptin injectionObese miceHypothalamic sitesLeptin treatment
2015
Astrocyte‐expressed FABP7 regulates dendritic morphology and excitatory synaptic function of cortical neurons
Ebrahimi M, Yamamoto Y, Sharifi K, Kida H, Kagawa Y, Yasumoto Y, Islam A, Miyazaki H, Shimamoto C, Maekawa M, Mitsushima D, Yoshikawa T, Owada Y. Astrocyte‐expressed FABP7 regulates dendritic morphology and excitatory synaptic function of cortical neurons. Glia 2015, 64: 48-62. PMID: 26296243, DOI: 10.1002/glia.22902.Peer-Reviewed Original ResearchConceptsFabp7 KO miceMedial prefrontal cortexMiniature excitatory postsynaptic currentsAberrant dendritic morphologyKO miceCortical neuronsDendritic morphologyNeuropsychiatric disordersWhole-cell voltage-clamp recordingsPrimary cortical neuronal culturesDendritic arbor growthNeuronal dendritic morphologyExcitatory synaptic functionCortical pyramidal neuronsExcitatory synapse numberCortical neuronal culturesExcitatory postsynaptic currentsAstrocyte-conditioned mediumPrimary cortical neuronsWild-type miceExcitatory synapse formationVoltage-clamp recordingsNovel therapeutic interventionsHuman neuropsychiatric disordersFatty acidsFatty acid‐binding protein 7 regulates function of caveolae in astrocytes through expression of caveolin‐1
Kagawa Y, Yasumoto Y, Sharifi K, Ebrahimi M, Islam A, Miyazaki H, Yamamoto Y, Sawada T, Kishi H, Kobayashi S, Maekawa M, Yoshikawa T, Takaki E, Nakai A, Kogo H, Fujimoto T, Owada Y. Fatty acid‐binding protein 7 regulates function of caveolae in astrocytes through expression of caveolin‐1. Glia 2015, 63: 780-794. PMID: 25601031, DOI: 10.1002/glia.22784.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornAstrocytesCaveolaeCaveolin 1Cell SurvivalCells, CulturedCerebral CortexCholesterolCytokinesFatty Acid-Binding Protein 7Fatty Acid-Binding ProteinsGene Expression ProfilingGene Expression RegulationGlial Cell Line-Derived Neurotrophic FactorLipopolysaccharidesMiceMice, Inbred C57BLMice, KnockoutNerve Tissue ProteinsOligonucleotide Array Sequence AnalysisSignal TransductionTransduction, GeneticConceptsLipid raft functionCaveolin-1Raft functionLipid raftsFatty Acid Binding Protein 7Function of caveolaeReceptor-mediated signal transductionMitogen-activated protein kinaseRole of FABP7Toll-like receptor 4Caveolin-1 expressionExtracellular stimuliCavin-1Protein bindsSignal transductionCaveolin-2Flotillin-1Protein kinaseReceptor alpha 1Transcriptional levelLong-chain fatty acidsLipid dynamicsWild-type astrocytesLipid homeostasisTLR4 recruitment
2014
Fatty Acid Binding Protein 3 Is Involved in n–3 and n–6 PUFA Transport in Mouse Trophoblasts
Islam A, Kagawa Y, Sharifi K, Ebrahimi M, Miyazaki H, Yasumoto Y, Kawamura S, Yamamoto Y, Sakaguti S, Sawada T, Tokuda N, Sugino N, Suzuki R, Owada Y. Fatty Acid Binding Protein 3 Is Involved in n–3 and n–6 PUFA Transport in Mouse Trophoblasts. Journal Of Nutrition 2014, 144: 1509-1516. PMID: 25122651, DOI: 10.3945/jn.114.197202.Peer-Reviewed Original ResearchConceptsWild-type micePlacental fatty acid transportFatty Acid Binding Protein 3Glucose uptakeLinoleic acidAdult metabolic diseaseBinding protein 3Fetal developmental disordersGene-ablated miceFA transportWild-type fetusesEmbryonic day 15.5Palmitic acidPlacental unitFatty acid transportMetabolic diseasesFetal developmentTrophoblast cellsBeWo cellsProtein 3Day 15.5MiceMouse placentaPlacentaMouse trophoblastFatty Acid Binding Protein 7 Regulates Phagocytosis and Cytokine Production in Kupffer Cells during Liver Injury
Miyazaki H, Sawada T, Kiyohira M, Yu Z, Nakamura K, Yasumoto Y, Kagawa Y, Ebrahimi M, Islam A, Sharifi K, Kawamura S, Kodama T, Yamamoto Y, Adachi Y, Tokuda N, Terai S, Sakaida I, Ishikawa T, Owada Y. Fatty Acid Binding Protein 7 Regulates Phagocytosis and Cytokine Production in Kupffer Cells during Liver Injury. American Journal Of Pathology 2014, 184: 2505-2515. PMID: 25041855, DOI: 10.1016/j.ajpath.2014.05.015.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, WesternCarbon TetrachlorideChemical and Drug Induced Liver InjuryCytokinesEnzyme-Linked Immunosorbent AssayFatty Acid-Binding Protein 7Fatty Acid-Binding ProteinsFlow CytometryFluorescent Antibody TechniqueImmunohistochemistryIn Situ Nick-End LabelingKupffer CellsMaleMiceMice, Inbred C57BLMice, KnockoutNerve Tissue ProteinsPhagocytosisReverse Transcriptase Polymerase Chain ReactionConceptsLiver injuryKupffer cellsKnockout miceLiver diseaseCytokine productionKC functionNumber of KCsKC phagocytic activityLiver injury processLiver necrotic areasChronic liver injurySerum liver enzymesWild-type miceNovel therapeutic approachesRole of FABP7Scavenger receptor CD36Cytokine expressionFibrogenic responseLiver enzymesInjury processPathological changesLiver cancerTherapeutic approachesReceptor CD36Tissue macrophages
2013
Differential expression and regulatory roles of FABP5 and FABP7 in oligodendrocyte lineage cells
Sharifi K, Ebrahimi M, Kagawa Y, Islam A, Tuerxun T, Yasumoto Y, Hara T, Yamamoto Y, Miyazaki H, Tokuda N, Yoshikawa T, Owada Y. Differential expression and regulatory roles of FABP5 and FABP7 in oligodendrocyte lineage cells. Cell And Tissue Research 2013, 354: 683-695. PMID: 24114376, DOI: 10.1007/s00441-013-1730-7.Peer-Reviewed Original ResearchConceptsLineage cellsOligodendrocyte lineage cellsOligodendrocyte progenitor cellsCultured oligodendrocyte progenitor cellsCell populationsOPCs/oligodendrocytesSignal transductionGene transcriptionKey intracellular moleculesOligodendrocyte lineage markersExpression of FABP5Differential expressionRegulatory roleIntracellular moleculesDifferentiation mediumFABP7FABP5FABP7 expressionLineage markersProgenitor cellsOligodendrocyte lineageMixed cortical culturesBrdU uptakeExpressionCentral rolePathological features of highly invasive glioma stem cells in a mouse xenograft model
Sadahiro H, Yoshikawa K, Ideguchi M, Kajiwara K, Ishii A, Ikeda E, Owada Y, Yasumoto Y, Suzuki M. Pathological features of highly invasive glioma stem cells in a mouse xenograft model. Brain Tumor Pathology 2013, 31: 77-84. PMID: 23670138, DOI: 10.1007/s10014-013-0149-x.Peer-Reviewed Original ResearchConceptsGlioma stem cellsMouse xenograft modelSubventricular zoneXenograft modelCorpus callosumTumor xenograft modelMatrigel invasion assaysGSC linesInvasive potentialHigh invasive potentialStem cellsPathological featuresMultimodal therapyContralateral hemisphereTumor bulkMouse brainTumor progressionHuman glioblastomaMigratory propertiesMigration abilityCallosumCells
2011
FABP7 expression in normal and stab-injured brain cortex and its role in astrocyte proliferation
Sharifi K, Morihiro Y, Maekawa M, Yasumoto Y, Hoshi H, Adachi Y, Sawada T, Tokuda N, Kondo H, Yoshikawa T, Suzuki M, Owada Y. FABP7 expression in normal and stab-injured brain cortex and its role in astrocyte proliferation. Histochemistry And Cell Biology 2011, 136: 501. PMID: 21938553, PMCID: PMC3192944, DOI: 10.1007/s00418-011-0865-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornAntigensAstrocytesCell ProliferationCells, CulturedCerebral CortexDisease Models, AnimalFatty Acid-Binding Protein 7Fatty Acid-Binding ProteinsFatty Acids, Omega-3Gene ExpressionGliosisHomeostasisMaleMiceMice, Inbred C57BLMice, KnockoutNerve Tissue ProteinsNeural Stem CellsOligodendrogliaProteoglycansWounds, StabConceptsFabp7 KO miceGlial cellsReactive gliosisFABP7 expressionBrain-type fatty acid-binding proteinProliferation of astrocytesExpression of FABP7Cellular fatty acid homeostasisWild-type miceGlial cell proliferationOligodendrocyte progenitor cellsWild-type astrocytesFatty acid-binding proteinRole of FABP7Fatty acid homeostasisFatty acid incorporationNeural stem cellsReactive astrocytesNormal cortexAstrocyte proliferationContralateral sideInjury modelAcid-binding proteinBrain pathologyBrain cortex