2023
SHANK3 in vagal sensory neurons regulates body temperature, systemic inflammation, and sepsis
Zhang L, Bang S, He Q, Matsuda M, Luo X, Jiang Y, Ji R. SHANK3 in vagal sensory neurons regulates body temperature, systemic inflammation, and sepsis. Frontiers In Immunology 2023, 14: 1124356. PMID: 36845137, PMCID: PMC9944123, DOI: 10.3389/fimmu.2023.1124356.Peer-Reviewed Original ResearchConceptsVagal sensory neuronsNodose ganglionSensory neuronsSystemic inflammationBody temperatureDorsal root ganglion sensory neuronsSerum IL-6 levelsAuricular vagus nerve stimulationBasal core temperatureIL-6 levelsVagus nerve stimulationAutism spectrum disorderRole of Shank3Conditional knockout miceSynaptic scaffolding proteinsSepsis mortalityNerve stimulationExcessive inflammationHeat painInflammation dysregulationKO miceKnockout miceInflammationSHANK3 expressionNovel molecular mechanism
2022
Vitamin C epigenetically controls osteogenesis and bone mineralization
Thaler R, Khani F, Sturmlechner I, Dehghani SS, Denbeigh JM, Zhou X, Pichurin O, Dudakovic A, Jerez SS, Zhong J, Lee JH, Natarajan R, Kalajzic I, Jiang YH, Deyle DR, Paschalis EP, Misof BM, Ordog T, van Wijnen AJ. Vitamin C epigenetically controls osteogenesis and bone mineralization. Nature Communications 2022, 13: 5883. PMID: 36202795, PMCID: PMC9537512, DOI: 10.1038/s41467-022-32915-8.Peer-Reviewed Original ResearchConceptsSevere skeletal defectsBone-specific genesEpigenetic functionsChromatin accessibilityHistone demethylationDNA hydroxymethylationTranscriptional activityPro-osteogenic genesCell differentiationOsteogenic cell differentiationOsteogenic differentiationGenesSkeletal defectsBone phenotypeMurine boneOsteoblastogenesisDifferentiationKnockout miceGulo knockout miceVitamin C deficiencyTET1Collagen maturationPromoterDemethylationVitamin CComparative Proteome and Cis-Regulatory Element Analysis Reveals Specific Molecular Pathways Conserved in Dog and Human Brains
Hong H, Zhao Z, Huang X, Guo C, Zhao H, Wang GD, Zhang YP, Zhao JP, Shi J, Wu QF, Jiang YH, Wang Y, Li LM, Du Z, Zhang YQ, Xiong Y. Comparative Proteome and Cis-Regulatory Element Analysis Reveals Specific Molecular Pathways Conserved in Dog and Human Brains. Molecular & Cellular Proteomics 2022, 21: 100261. PMID: 35738554, PMCID: PMC9304787, DOI: 10.1016/j.mcpro.2022.100261.Peer-Reviewed Original ResearchNeural circuit pathology driven by Shank3 mutation disrupts social behaviors
Kim S, Kim YE, Song I, Ujihara Y, Kim N, Jiang YH, Yin HH, Lee TH, Kim IH. Neural circuit pathology driven by Shank3 mutation disrupts social behaviors. Cell Reports 2022, 39: 110906. PMID: 35675770, PMCID: PMC9210496, DOI: 10.1016/j.celrep.2022.110906.Peer-Reviewed Original ResearchConceptsAutism spectrum disorderAlters spine morphologyWild-type miceExcitatory-inhibitory balanceSocial dysfunctionHuman ASD patientsMultiple brain regionsSocial behaviorElevated neural activityCircuit pathologyPathogenic mechanismsSHANK3 mutationsCircuit inhibitionBrain regionsCircuit activationNeural network mechanismReduced sociabilitySpine morphologyCore symptomsASD patientsPrefrontal cortexMiceSHANK3 geneNeural activitySpectrum disorderBrain-wide electrical dynamics encode individual appetitive social behavior
Mague SD, Talbot A, Blount C, Walder-Christensen KK, Duffney LJ, Adamson E, Bey AL, Ndubuizu N, Thomas GE, Hughes DN, Grossman Y, Hultman R, Sinha S, Fink AM, Gallagher NM, Fisher RL, Jiang YH, Carlson DE, Dzirasa K. Brain-wide electrical dynamics encode individual appetitive social behavior. Neuron 2022, 110: 1728-1741.e7. PMID: 35294900, PMCID: PMC9126093, DOI: 10.1016/j.neuron.2022.02.016.Peer-Reviewed Original ResearchInhibition of Trpv4 rescues circuit and social deficits unmasked by acute inflammatory response in a Shank3 mouse model of Autism
Tzanoulinou S, Musardo S, Contestabile A, Bariselli S, Casarotto G, Magrinelli E, Jiang YH, Jabaudon D, Bellone C. Inhibition of Trpv4 rescues circuit and social deficits unmasked by acute inflammatory response in a Shank3 mouse model of Autism. Molecular Psychiatry 2022, 27: 2080-2094. PMID: 35022531, PMCID: PMC9126815, DOI: 10.1038/s41380-021-01427-0.Peer-Reviewed Original ResearchConceptsAcute inflammatory responseInflammatory responseSHANK3 geneTransient receptor potential vanilloid 4Shank3 mouse modelAutism spectrum disorderGenetic risk factorsInhibition of TRPV4Ex vivo approachNeuron hyperexcitabilityRisk factorsBehavioral deficitsNucleus accumbensMouse modelTRPV4 inhibitionBehavioral alterationsSocial deficitsSHANK3 mutationsCircuit mechanismsNeurodevelopmental diseasesGenetic alterationsTypes of mutationsHeterozygous deletionIdiopathic autismEnvironmental insults
2020
A Novel Chd8 Mutant Mouse Displays Altered Ultrasonic Vocalizations and Enhanced Motor Coordination
Hulbert SW, Wang X, Gbadegesin SO, Xu Q, Xu X, Jiang Y. A Novel Chd8 Mutant Mouse Displays Altered Ultrasonic Vocalizations and Enhanced Motor Coordination. Autism Research 2020, 13: 1685-1697. PMID: 32815320, PMCID: PMC7780289, DOI: 10.1002/aur.2353.Peer-Reviewed Original Research
2019
Potassium channel dysfunction in human neuronal models of Angelman syndrome
Sun A, Yuan Q, Fukuda M, Yu W, Yan H, Lim G, Nai M, D'Agostino G, Tran H, Itahana Y, Wang D, Lokman H, Itahana K, Lim S, Tang J, Chang Y, Zhang M, Cook S, Rackham O, Lim C, Tan E, Ng H, Lim K, Jiang Y, Je H. Potassium channel dysfunction in human neuronal models of Angelman syndrome. Science 2019, 366: 1486-1492. PMID: 31857479, PMCID: PMC7735558, DOI: 10.1126/science.aav5386.Peer-Reviewed Original ResearchConceptsAngelman syndromePotassium channel dysfunctionAS mouse modelUbiquitin protein ligase E3A (UBE3A) geneHuman neuronal modelNeuronal hyperexcitabilityNetwork hyperactivityAS patientsSeizure susceptibilitySynaptic dysfunctionModel miceIntrinsic excitabilityNeuronal excitabilityMouse modelBig potassium channelsHuman neuronsChannel dysfunctionEpilepsy susceptibilityBK channelopathyMouse neuronsPotassium channelsIndividual neuronsBrain organoidsNeuronsDysfunctionANK2 autism mutation targeting giant ankyrin-B promotes axon branching and ectopic connectivity
Yang R, Walder-Christensen KK, Kim N, Wu D, Lorenzo DN, Badea A, Jiang YH, Yin HH, Wetsel WC, Bennett V. ANK2 autism mutation targeting giant ankyrin-B promotes axon branching and ectopic connectivity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 15262-15271. PMID: 31285321, PMCID: PMC6660793, DOI: 10.1073/pnas.1904348116.Peer-Reviewed Original ResearchMeSH KeywordsAlternative SplicingAnimalsAnkyrinsAutism Spectrum DisorderBehavior, AnimalCell MembraneConnectomeDisease Models, AnimalExecutive FunctionGene ExpressionGene Knock-In TechniquesHumansMaleMiceMice, TransgenicMicrotubulesMutationNeural Cell Adhesion Molecule L1Neuronal OutgrowthNeuronsPrimary Cell CultureSocial BehaviorSynapsesEpigenetic therapy of Prader–Willi syndrome
Kim Y, Wang SE, Jiang YH. Epigenetic therapy of Prader–Willi syndrome. Translational Research 2019, 208: 105-118. PMID: 30904443, PMCID: PMC6527448, DOI: 10.1016/j.trsl.2019.02.012.Peer-Reviewed Original ResearchConceptsPWS mouse modelEpigenetic-based therapiesMaternal chromosomesImprinted gene regulationEHMT2/G9aLysine 9 methyltransferasePatient-derived fibroblastsPrader-Willi syndromeGene regulationMethyltransferase SETDB1Epigenetic mechanismsSmall molecule librariesPWS genesHigh-content screeningSame genePerinatal lethalityEpigenetic therapyFusion proteinMolecular mechanismsG9a inhibitorChromosomesSNORD116 clusterGenesMolecular defectsPatient iPSC
2018
Autism-associated CHD8 deficiency impairs axon development and migration of cortical neurons
Xu Q, Liu YY, Wang X, Tan GH, Li HP, Hulbert SW, Li CY, Hu CC, Xiong ZQ, Xu X, Jiang YH. Autism-associated CHD8 deficiency impairs axon development and migration of cortical neurons. Molecular Autism 2018, 9: 65. PMID: 30574290, PMCID: PMC6299922, DOI: 10.1186/s13229-018-0244-2.Peer-Reviewed Original ResearchConceptsCHD8 deficiencyNeuronal migrationChromodomain helicase DNAMouse brainChromatin structureTranscriptional regulatorsParvalbumin-positive neuronsHistone H1Autism spectrum disorderGenetic studiesCHD8Protein 8Functional consequencesNovel insightsBiochemical analysisContralateral cortexSitu hybridizationCortical neuronsCommon findingUtero electroporationGlia cellsNeuronal culturesAxon projectionsDeficiency impairsCircuit mechanismsEpigenetic dysregulation of Oxtr in Tet1-deficient mice has implications for neuropsychiatric disorders
Towers AJ, Tremblay MW, Chung L, Li XL, Bey AL, Zhang W, Cao X, Wang X, Wang P, Duffney LJ, Siecinski SK, Xu S, Kim Y, Kong X, Gregory S, Xie W, Jiang YH. Epigenetic dysregulation of Oxtr in Tet1-deficient mice has implications for neuropsychiatric disorders. JCI Insight 2018, 3: e120592. PMID: 30518695, PMCID: PMC6328031, DOI: 10.1172/jci.insight.120592.Peer-Reviewed Original ResearchCRISPR/Cas9-mediated disruption of SHANK3 in monkey leads to drug-treatable autism-like symptoms
Tu Z, Zhao H, Li B, Yan S, Wang L, Tang Y, Li Z, Bai D, Li C, Lin Y, Li Y, Liu J, Xu H, Guo X, Jiang YH, Zhang YQ, Li XJ. CRISPR/Cas9-mediated disruption of SHANK3 in monkey leads to drug-treatable autism-like symptoms. Human Molecular Genetics 2018, 28: 561-571. PMID: 30329048, PMCID: PMC6489410, DOI: 10.1093/hmg/ddy367.Peer-Reviewed Original ResearchConceptsAutism spectrum disorderCynomolgus monkey modelAutism-like symptomsPathogenesis of ASDPostsynaptic scaffold proteinsNon-human primatesFluoxetine treatmentBrain network activityMonkey modelMouse modelBehavioral abnormalitiesCausative roleExperimental therapeuticsSHANK3 mutationsBrain structuresSHANK3 geneTranslational researchMonogenic mutationsBrain activitySpecies-dependent differencesPositron emissionNetwork activityCRISPR/Cas9-mediated disruptionMonkeysSpectrum disorderEarly Correction of N-Methyl-D-Aspartate Receptor Function Improves Autistic-like Social Behaviors in Adult Shank2 −/− Mice
Chung C, Ha S, Kang H, Lee J, Um SM, Yan H, Yoo YE, Yoo T, Jung H, Lee D, Lee E, Lee S, Kim J, Kim R, Kwon Y, Kim W, Kim H, Duffney L, Kim D, Mah W, Won H, Mo S, Kim JY, Lim CS, Kaang BK, Boeckers TM, Chung Y, Kim H, Jiang YH, Kim E. Early Correction of N-Methyl-D-Aspartate Receptor Function Improves Autistic-like Social Behaviors in Adult Shank2 −/− Mice. Biological Psychiatry 2018, 85: 534-543. PMID: 30466882, PMCID: PMC6420362, DOI: 10.1016/j.biopsych.2018.09.025.Peer-Reviewed Original ResearchConceptsAutism spectrum disorderSocial behaviorSpectrum disorderAutistic-like phenotypesLate pathophysiologyNMDAR hypofunctionHuman autism spectrum disorderNMDAR hyperfunctionN-methyl-D-aspartate (NMDA) receptor hypofunctionAutistic-like behaviorsNMDAR antagonist memantineAspartate Receptor FunctionEarly pathophysiologyPup stageEarly correctionAdult miceBehavioral analysisNMDAR dysfunctionPostnatal day 21Receptor hypofunctionChronic suppressionAnimal studiesDay 21HypofunctionDisordersPAK2 Haploinsufficiency Results in Synaptic Cytoskeleton Impairment and Autism-Related Behavior
Wang Y, Zeng C, Li J, Zhou Z, Ju X, Xia S, Li Y, Liu A, Teng H, Zhang K, Shi L, Bi C, Xie W, He X, Jia Z, Jiang Y, Cai T, Wu J, Xia K, Sun Z. PAK2 Haploinsufficiency Results in Synaptic Cytoskeleton Impairment and Autism-Related Behavior. Cell Reports 2018, 24: 2029-2041. PMID: 30134165, DOI: 10.1016/j.celrep.2018.07.061.Peer-Reviewed Original Research
2017
Lovastatin suppresses hyperexcitability and seizure in Angelman syndrome model
Chung L, Bey AL, Towers AJ, Cao X, Kim IH, Jiang YH. Lovastatin suppresses hyperexcitability and seizure in Angelman syndrome model. Neurobiology Of Disease 2017, 110: 12-19. PMID: 29097328, PMCID: PMC5903876, DOI: 10.1016/j.nbd.2017.10.016.Peer-Reviewed Original ResearchConceptsEpileptiform activityMouse modelAngelman syndrome modelFragile X syndrome mouse modelLower seizure thresholdSyndrome mouse modelNeural mechanismsAngelman syndromeSeizure thresholdSynaptic dysfunctionAudiogenic seizuresExcitatory neurotransmissionLocal circuitsSyndrome modelSeizuresUBE3ADrug screeningFXS modelsHyperexcitabilitySupDysfunctionEpilepsyNeurotransmissionSyndromeDissectionDeficiency of Shank2 causes mania-like behavior that responds to mood stabilizers
Pappas A, Bey A, Wang X, Rossi M, Kim Y, Yan H, Porkka F, Duffney L, Phillips S, Cao X, Ding J, Rodriguiz R, Yin H, Weinberg R, Ji R, Wetsel W, Jiang Y. Deficiency of Shank2 causes mania-like behavior that responds to mood stabilizers. JCI Insight 2017, 2: e92052. PMID: 29046483, PMCID: PMC5846902, DOI: 10.1172/jci.insight.92052.Peer-Reviewed Original ResearchAmphetamineAnhedoniaAnimalsAntimanic AgentsBehavior, AnimalBipolar DisorderCentral Nervous System StimulantsChronobiology DisordersCognitive DysfunctionFemaleHippocampusLithium CompoundsMaleMiceMice, KnockoutMotor ActivityN-MethylaspartateNerve Tissue ProteinsPhenotypeProsencephalonReceptors, AMPAReceptors, N-Methyl-D-AspartateSocial Behavior DisordersSynapsesCellular and Circuitry Bases of Autism: Lessons Learned from the Temporospatial Manipulation of Autism Genes in the Brain
Hulbert SW, Jiang YH. Cellular and Circuitry Bases of Autism: Lessons Learned from the Temporospatial Manipulation of Autism Genes in the Brain. Neuroscience Bulletin 2017, 33: 205-218. PMID: 28271437, PMCID: PMC5360850, DOI: 10.1007/s12264-017-0112-7.Peer-Reviewed Original ResearchConceptsAutism spectrum disorderDifferent neurotransmitter systemsCell typesNeurotransmitter systemsInhibitory neuronsAdult miceTransgenic miceBrain regionsCre linesDevelopmental time periodCre-loxPCertain cell typesMiceCore ASD symptomsDisordersMolecular underpinningsTime periodSpectrum disorderASD symptomsGene expressionMutations
2016
Targeting the histone methyltransferase G9a activates imprinted genes and improves survival of a mouse model of Prader–Willi syndrome
Kim Y, Lee HM, Xiong Y, Sciaky N, Hulbert SW, Cao X, Everitt JI, Jin J, Roth BL, Jiang YH. Targeting the histone methyltransferase G9a activates imprinted genes and improves survival of a mouse model of Prader–Willi syndrome. Nature Medicine 2016, 23: 213-222. PMID: 28024084, PMCID: PMC5589073, DOI: 10.1038/nm.4257.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, WesternCell LineDisease Models, AnimalEnzyme InhibitorsEpigenesis, GeneticFemaleFibroblastsGene ExpressionGenomic ImprintingHistone CodeHistone-Lysine N-MethyltransferaseHumansImmunohistochemistryMaleMethylationMicePrader-Willi SyndromeQuinazolinesReverse Transcriptase Polymerase Chain ReactionRNA, Small NucleolarSnRNP Core ProteinsSurvival RateUbiquitin-Protein LigasesSHANK3 Deficiency Impairs Heat Hyperalgesia and TRPV1 Signaling in Primary Sensory Neurons
Han Q, Kim YH, Wang X, Liu D, Zhang ZJ, Bey AL, Lay M, Chang W, Berta T, Zhang Y, Jiang YH, Ji RR. SHANK3 Deficiency Impairs Heat Hyperalgesia and TRPV1 Signaling in Primary Sensory Neurons. Neuron 2016, 92: 1279-1293. PMID: 27916453, PMCID: PMC5182147, DOI: 10.1016/j.neuron.2016.11.007.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBehavior, AnimalBlotting, WesternCapsaicinGanglia, SpinalHumansHyperalgesiaImmunohistochemistryInflammationMiceMice, KnockoutMicrofilament ProteinsNAV1.8 Voltage-Gated Sodium ChannelNerve Tissue ProteinsNeuralgiaPainPatch-Clamp TechniquesPresynaptic TerminalsReverse Transcriptase Polymerase Chain ReactionSensory Receptor CellsSensory System AgentsSpinal CordTRPV Cation ChannelsConceptsHeat hyperalgesiaSensory neuronsDRG neuronsMouse dorsal root ganglion sensory neuronsDorsal root ganglion sensory neuronsCapsaicin-induced spontaneous painAbnormal pain sensitivityHuman DRG neuronsPrimary sensory neuronsAutism spectrum disorderSpinal cord neuronsSpontaneous painTRPV1 signalingNeuropathic painPain sensitivityPeripheral mechanismsCord neuronsSHANK3 haploinsufficiencyTRPV1 functionPresynaptic terminalsSynaptic currentsPain deficitsSHANK3 deficiencyInward currentsSHANK3 expression