2024
Transcriptional determinism and stochasticity contribute to the complexity of autism-associated SHANK family genes
Lu X, Ni P, Suarez-Meade P, Ma Y, Forrest E, Wang G, Wang Y, Quiñones-Hinojosa A, Gerstein M, Jiang Y. Transcriptional determinism and stochasticity contribute to the complexity of autism-associated SHANK family genes. Cell Reports 2024, 43: 114376. PMID: 38900637, PMCID: PMC11328446, DOI: 10.1016/j.celrep.2024.114376.Peer-Reviewed Original ResearchSHANK family genesFamily genesLong-read sequencingCDNA captureTranscript structureDeleterious variantsGenomic studiesAbundant mRNAsTranscriptional dysregulationStochastic transcriptionStudies of neuropsychiatric disordersCausative genesTranscriptional profilesTranscriptional determinantsTranscriptomePostmortem brain tissueAutism spectrum disorderShank3 transcriptsTranscriptionGenesGenomeSHANK3Neuropsychiatric disordersSpectrum disorderAutism modelImpaired synaptic function and hyperexcitability of the pyramidal neurons in the prefrontal cortex of autism-associated Shank3 mutant dogs
Zhu F, Shi Q, Jiang Y, Zhang Y, Zhao H. Impaired synaptic function and hyperexcitability of the pyramidal neurons in the prefrontal cortex of autism-associated Shank3 mutant dogs. Molecular Autism 2024, 15: 9. PMID: 38297387, PMCID: PMC10829216, DOI: 10.1186/s13229-024-00587-4.Peer-Reviewed Original ResearchConceptsPrefrontal cortexPyramidal neuronsSHANK3 mutationsPrefrontal cortex neuronal activityPrefrontal cortex pyramidal neuronsSocial behaviorBrain slicesPrefrontal cortex's roleSynaptic transmissionPrefrontal cortex layersStudy social cognitionAutism spectrum disorderAutism-like behaviorsDendritic spine morphologyReduced dendritic complexitySocial cognitionSocial impairmentBehavioral alterationsNeural mechanismsExcitatory synaptic transmissionMutant rodent modelsHeightened anxietySpectrum disorderSpine densityImpaired synaptic function
2023
Modeling SHANK3-associated autism spectrum disorder in Beagle dogs via CRISPR/Cas9 gene editing
Tian R, Li Y, Zhao H, Lyu W, Zhao J, Wang X, Lu H, Xu H, Ren W, Tan Q, Shi Q, Wang G, Zhang Y, Lai L, Mi J, Jiang Y, Zhang Y. Modeling SHANK3-associated autism spectrum disorder in Beagle dogs via CRISPR/Cas9 gene editing. Molecular Psychiatry 2023, 28: 3739-3750. PMID: 37848710, DOI: 10.1038/s41380-023-02276-9.Peer-Reviewed Original ResearchConceptsAutism spectrum disorderSpectrum disorderNon-human primatesDog-human social interactionsPreclinical studiesBattery of behavioral assaysSocial behavior deficitsASD mouse modelsSocial interactionReduced social interactionCRISPR/Cas9 gene editingGenetic mutant miceNeural circuit mechanismsSocial withdrawalBehavioral findingsPsychiatric disordersBehavioral deficitsHeightened anxietyCanine modelSHANK3 mutationsSHANK3 geneCircuit mechanismsMutant miceMouse modelBehavioral assays
2022
Neural 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 disorderInhibition 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
2021
Differential Metabolites in Chinese Autistic Children: A Multi-Center Study Based on Urinary 1H-NMR Metabolomics Analysis
Ma Y, Zhou H, Li C, Zou X, Luo X, Wu L, Li T, Chen X, Mao M, Huang Y, Li E, An Y, Zhang L, Wang T, Xu X, Yan W, Jiang Y, Wang Y. Differential Metabolites in Chinese Autistic Children: A Multi-Center Study Based on Urinary 1H-NMR Metabolomics Analysis. Frontiers In Psychiatry 2021, 12: 624767. PMID: 34045978, PMCID: PMC8144639, DOI: 10.3389/fpsyt.2021.624767.Peer-Reviewed Original ResearchDifferential metabolitesHealthy childrenPathogenic mechanismsControl groupGuanidinoacetic acidAutism spectrum disorderROC curveMulti-center studyCharacteristic curve analysisH NMR metabolomics analysisSignificant diagnostic valueAmino acid metabolitesMetabolomic analysisN-methylnicotinamideEarly-onset neurodevelopmental disorderUnivariate analysisEarly diagnosisValuable biomarkerAcid metabolitesAmino acid metabolic pathwaysDiagnostic valueAutistic childrenCreatinineCurve analysisMetabolic variationsPsychometric properties of the Chinese Parent Version of the Autism Spectrum Rating Scale: Rasch analysis
Yan W, Siegert RJ, Zhou H, Zou X, Wu L, Luo X, Li T, Huang Y, Guan H, Chen X, Mao M, Xia K, Zhang L, Li E, Li C, Zhang X, Zhou Y, Shih A, Fombonne E, Zheng Y, Han J, Sun Z, Jiang YH, Wang Y. Psychometric properties of the Chinese Parent Version of the Autism Spectrum Rating Scale: Rasch analysis. Autism 2021, 25: 1872-1884. PMID: 33845648, PMCID: PMC8548063, DOI: 10.1177/13623613211004054.Peer-Reviewed Original ResearchConceptsAutism Spectrum Rating ScaleAutism spectrum disorderSpectrum disorderRasch analysisRating ScaleBehavioral rating scalesIdentification of childrenParent versionRasch measurementPsychometric propertiesChinese childrenChildrenDisordersParentsSupport servicesScaleStringent criteriaItemsGrandparentsScientific measurementsQuestionnaireBehavior characteristicsTeachers
2020
Altered striatum centered brain structures in SHANK3 deficient Chinese children with genotype and phenotype profiling
Liu C, Li D, Yang H, Li H, Xu Q, Zhou B, Hu C, Li C, Wang Y, Qiao Z, Jiang YH, Xu X. Altered striatum centered brain structures in SHANK3 deficient Chinese children with genotype and phenotype profiling. Progress In Neurobiology 2020, 200: 101985. PMID: 33388374, PMCID: PMC8572121, DOI: 10.1016/j.pneurobio.2020.101985.Peer-Reviewed Original ResearchConceptsTract-based spatial statisticsVoxel-based morphometryUnderlying neuropathological mechanismsNeuropathological mechanismsDeficient childrenBrain structuresMiddle cerebral peduncleAutism spectrum disorderAbnormal neural circuitsPosterior thalamic radiationGray matter volumeFunctional connectivity studiesSuperior longitudinal fasciculusStudy of subjectsCerebral peduncleInternal capsuleRisk factorsDental abnormalitiesCorpus callosumCommissural fibersHematological problemsCorona radiataDorsal striatumNeurobehavioral evaluationAnteverted naresThe role of Hipk2-p53 pathways in arsenic-induced autistic behaviors: A translational study from rats to humans
Zhou H, Lin Y, Zhao W, Teng Y, Cui Y, Wang T, Li C, Jiang YH, Zhang JJ, Wang Y. The role of Hipk2-p53 pathways in arsenic-induced autistic behaviors: A translational study from rats to humans. Environmental Pollution 2020, 267: 115568. PMID: 33254717, DOI: 10.1016/j.envpol.2020.115568.Peer-Reviewed Original ResearchConceptsCase-control studySerum levelsArsenic exposureHealthy controlsNeuronal apoptosisFrontal cortexAge-matched healthy controlsGestational arsenic exposureHuman case-control studiesASD developmentHigher serum levelsAutistic behaviorASD childrenDose-dependent mannerAutism spectrum disorderPotential mediating pathwaysRat modelRat pupsKey molecular changesImmunohistochemistry analysisTranslational studiesWestern blottingMolecular changesTranslational strategiesMediating pathwaysPrevalence of Autism Spectrum Disorder in China: A Nationwide Multi-center Population-based Study Among Children Aged 6 to 12 Years
Zhou H, Xu X, Yan W, Zou X, Wu L, Luo X, Li T, Huang Y, Guan H, Chen X, Mao M, Xia K, Zhang L, Li E, Ge X, Zhang L, Li C, Zhang X, Zhou Y, Ding D, Shih A, Fombonne E, Zheng Y, Han J, Sun Z, Jiang YH, Wang Y. Prevalence of Autism Spectrum Disorder in China: A Nationwide Multi-center Population-based Study Among Children Aged 6 to 12 Years. Neuroscience Bulletin 2020, 36: 961-971. PMID: 32607739, PMCID: PMC7475160, DOI: 10.1007/s12264-020-00530-6.Peer-Reviewed Original ResearchConceptsAutism spectrum disorderMulti-centre populationChildren Aged 6Chinese childrenASD casesFirst national estimatesNeuropsychiatric comorbiditiesTarget population samplePrevalence studyPrevalence ratesSpectrum disorderAged 6Response rateASD prevalence ratesOverall populationNational estimatesPrevalenceRating ScaleASD prevalenceComorbiditiesChildrenPopulation sampleTarget populationConvenient clusterDisorders
2019
Maternal valproic acid exposure leads to neurogenesis defects and autism-like behaviors in non-human primates
Zhao H, Wang Q, Yan T, Zhang Y, Xu H, Yu H, Tu Z, Guo X, Jiang Y, Li X, Zhou H, Zhang Y. Maternal valproic acid exposure leads to neurogenesis defects and autism-like behaviors in non-human primates. Translational Psychiatry 2019, 9: 267. PMID: 31636273, PMCID: PMC6803711, DOI: 10.1038/s41398-019-0608-1.Peer-Reviewed Original ResearchConceptsNon-human primatesVPA exposurePrefrontal cortexNeuN-positive mature neuronsGFAP-positive astrocytesValproic acid exposureAutism-like behaviorsAutism spectrum disorderCerebellar external granular layerImpaired social interactionMaternal exposureAntiepileptic drugsExternal granular layerRisk factorsVariable presentationMature neuronsMurine modelRodent modelsEpidemiological studiesAcid exposureNeurogenesis defectsNeuronal precursorsEmbryonic brainNeurodevelopmental defectsSimilar exposure
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 mechanismsCRISPR/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 ResearchConceptsAutism spectrum disorderCentral nervous systemLong-term potentiationDefective long-term potentiationCommon pathogenesisFunctional resultsSynapse density
2017
Cellular 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
SHANK3 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 expressionAltered mGluR5-Homer scaffolds and corticostriatal connectivity in a Shank3 complete knockout model of autism
Wang X, Bey AL, Katz BM, Badea A, Kim N, David LK, Duffney LJ, Kumar S, Mague SD, Hulbert SW, Dutta N, Hayrapetyan V, Yu C, Gaidis E, Zhao S, Ding JD, Xu Q, Chung L, Rodriguiz RM, Wang F, Weinberg RJ, Wetsel WC, Dzirasa K, Yin H, Jiang YH. Altered mGluR5-Homer scaffolds and corticostriatal connectivity in a Shank3 complete knockout model of autism. Nature Communications 2016, 7: 11459. PMID: 27161151, PMCID: PMC4866051, DOI: 10.1038/ncomms11459.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutism Spectrum DisorderBehavior, AnimalCerebral CortexCorpus StriatumFemaleHomer Scaffolding ProteinsHumansLong-Term Synaptic DepressionMaleMiceMice, KnockoutMicrofilament ProteinsModels, NeurologicalNerve NetNerve Tissue ProteinsReceptor, Metabotropic Glutamate 5Sequence DeletionSocial BehaviorConceptsASD-like behaviorsCircuit mechanismsStriatal synaptic plasticityAutism spectrum disorderAbnormal brain morphologyPathophysiology of ASDNeural circuit mechanismsHuman neuroimaging studiesKnockout mouse modelAberrant neural connectivityCircuit abnormalitiesStriatal neuronsStriatal synapsesCorticostriatal connectivityBehavioral deficitsAberrant structural connectivityMouse modelThalamic circuitsExcessive groomingSynaptic plasticityBrain morphologyNeuroimaging studiesSHANK3 geneNeural connectivityKnockout modelsChromosomal microarray analysis in clinical evaluation of neurodevelopmental disorders-reporting a novel deletion of SETDB1 and illustration of counseling challenge
Xu Q, Goldstein J, Wang P, Gadi IK, Labreche H, Rehder C, Wang WP, McConkie A, Xu X, Jiang YH. Chromosomal microarray analysis in clinical evaluation of neurodevelopmental disorders-reporting a novel deletion of SETDB1 and illustration of counseling challenge. Pediatric Research 2016, 80: 371-381. PMID: 27119313, PMCID: PMC5382808, DOI: 10.1038/pr.2016.101.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAlgorithmsAutistic DisorderChildChild, PreschoolChromatinComparative Genomic HybridizationCounselingDevelopmental DisabilitiesDNA Copy Number VariationsFemaleGene DeletionGene RearrangementHistone-Lysine N-MethyltransferaseHumansInfantIntellectual DisabilityMaleMicroarray AnalysisNeurodevelopmental DisordersPedigreeProtein MethyltransferasesConceptsNeurodevelopmental disordersAutism spectrum disorderIntellectual disabilityDevelopmental disabilitiesCopy number variationsChromosomal microarray analysisEtiological evaluationClinical evaluationClinical significanceUnknown significanceCNV analysisGenetics clinicEtiology of ASDCounseling familiesDisordersVariable penetranceClinicMicroarray analysisNovel deletionSpectrum disorderDisabilityCounseling challengesFurther supportEtiologyCohort
2015
Validity and reliability analysis of the Chinese parent version of the Autism Spectrum Rating Scale (6–18 years)
Zhou H, Zhang L, Wu L, Zou X, Luo X, Xia K, Wang Y, Xu X, Ge X, Sun C, Deng H, Fombonne E, Jiang YH, Yan W, Wang Y. Validity and reliability analysis of the Chinese parent version of the Autism Spectrum Rating Scale (6–18 years). Psychiatry Research 2015, 230: 255-261. PMID: 26384573, DOI: 10.1016/j.psychres.2015.09.003.Peer-Reviewed Original ResearchConceptsParent versionRating ScaleCommunity-based subjectsClinic-based participantsChinese childrenAutism spectrum disorderTest-retest reliabilityReceiver Operating Characteristic (ROC) analysisOperating characteristics analysisTotal scoreSocial Responsiveness ScaleChinese versionSignificant differencesConcurrent validityValid toolSymptomsAutistic symptomsInternal consistencyConstruct validityCharacteristic analysisSpectrum disorderDiscriminant validity