2022
Mispatterning and interneuron deficit in Tourette Syndrome basal ganglia organoids
Brady M, Mariani J, Koca Y, Szekely A, King R, Bloch M, Landeros-Weisenberger A, Leckman J, Vaccarino F. Mispatterning and interneuron deficit in Tourette Syndrome basal ganglia organoids. Molecular Psychiatry 2022, 27: 5007-5019. PMID: 36447010, PMCID: PMC9949887, DOI: 10.1038/s41380-022-01880-5.Peer-Reviewed Original ResearchConceptsTourette syndromeInterneuron deficitsGABAergic interneuronsHealthy controlsNeurodevelopmental underpinningsNeuropathological deficitsBG circuitryNeuropsychiatric disordersDecreased differentiationT patientsInterneuronsAltered expressionPotential mechanismsCilia disruptionSonic hedgehogOrganoidsStem cellsTS individualsPluripotent stem cellsGli transcription factorsDeficitsOrganoid differentiationEarly stagesCholinergicPatients
2015
Targeted ablation of cholinergic interneurons in the dorsolateral striatum produces behavioral manifestations of Tourette syndrome
Xu M, Kobets A, Du JC, Lennington J, Li L, Banasr M, Duman RS, Vaccarino FM, DiLeone RJ, Pittenger C. Targeted ablation of cholinergic interneurons in the dorsolateral striatum produces behavioral manifestations of Tourette syndrome. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 893-898. PMID: 25561540, PMCID: PMC4311862, DOI: 10.1073/pnas.1419533112.Peer-Reviewed Original ResearchConceptsTourette syndromeCholinergic interneuronsDorsolateral striatumSensorimotor gatingD-amphetamine challengeLarge cholinergic interneuronsSpecific cell ablationInterneuron deficitsStriatal interneuronsAcute administrationGABAergic markersDopaminergic drugsAvailable treatmentsPostmortem studiesPrepulse inhibitionTic disordersSevere diseaseHuman putamenMotor coordinationInterneuronsTargeted ablationSevere endStriatumAcute stressGilles de
2014
Transcriptome Analysis of the Human Striatum in Tourette Syndrome
Lennington JB, Coppola G, Kataoka-Sasaki Y, Fernandez TV, Palejev D, Li Y, Huttner A, Pletikos M, Sestan N, Leckman JF, Vaccarino FM. Transcriptome Analysis of the Human Striatum in Tourette Syndrome. Biological Psychiatry 2014, 79: 372-382. PMID: 25199956, PMCID: PMC4305353, DOI: 10.1016/j.biopsych.2014.07.018.Peer-Reviewed Original ResearchConceptsCopy number variantsGenome-wide association studiesGene coexpression modulesNumber variantsGene network analysisCommon genetic variantsCoexpression modulesUpregulated genesMetabolism modulesImmune-related genesNetwork analysisAssociation studiesDifferential expressionUpregulated modulesGenetic variantsGenesPatient's striatumTS individualsTranscriptomeVariantsMetabolic alterationsSame regionGamma-aminobutyric acidergic interneuronsTranscriptsRNA
2009
Decreased number of parvalbumin and cholinergic interneurons in the striatum of individuals with Tourette syndrome
Kataoka Y, Kalanithi PS, Grantz H, Schwartz ML, Saper C, Leckman JF, Vaccarino FM. Decreased number of parvalbumin and cholinergic interneurons in the striatum of individuals with Tourette syndrome. The Journal Of Comparative Neurology 2009, 518: 277-291. PMID: 19941350, PMCID: PMC2846837, DOI: 10.1002/cne.22206.Peer-Reviewed Original ResearchConceptsMedium spiny neuronsCholinergic interneuronsTourette syndromeNormal controlsCholinergic striatal interneuronsNumber of parvalbuminBrains of patientsCaudate nucleus volumeUnbiased stereological analysisStriatal interneuronsOngoing motor behaviorCholinergic cellsTotal neuronsCholine acetyltransferaseSpiny neuronsLimbic regionsStriatum of individualsTS patientsPostmortem brainsThalamic controlSensorimotor regionsInterneuronsCellular abnormalitiesNeuron firingTS subjects
2006
Annotation: Tourette syndrome: a relentless drumbeat – driven by misguided brain oscillations
Leckman JF, Vaccarino FM, Kalanithi PS, Rothenberger A. Annotation: Tourette syndrome: a relentless drumbeat – driven by misguided brain oscillations. Journal Of Child Psychology And Psychiatry 2006, 47: 537-550. PMID: 16712630, DOI: 10.1111/j.1469-7610.2006.01620.x.Peer-Reviewed Original ResearchConceptsTourette syndromeNormal central nervous system functionCentral nervous system functionNeural oscillationsAberrant neural oscillationsSuccessful behavioral treatmentNervous system functionMotor actionsSurgical interventionThalamocortical rhythmsElectrophysiological effectsElectrophysiological findingsSensorimotor gatingSensory urgeSynaptic plasticityTic suppressionAmeliorative effectBehavioral treatmentMotor responsePrefrontal cortexAberrant oscillationsCoherent network activityEffective modulatorPrefrontal regionsRecent evidence
2005
Altered parvalbumin-positive neuron distribution in basal ganglia of individuals with Tourette syndrome
Kalanithi PS, Zheng W, Kataoka Y, DiFiglia M, Grantz H, Saper CB, Schwartz ML, Leckman JF, Vaccarino FM. Altered parvalbumin-positive neuron distribution in basal ganglia of individuals with Tourette syndrome. Proceedings Of The National Academy Of Sciences Of The United States Of America 2005, 102: 13307-13312. PMID: 16131542, PMCID: PMC1201574, DOI: 10.1073/pnas.0502624102.Peer-Reviewed Original ResearchConceptsTourette syndromeNeuron distributionCalcium-binding protein parvalbuminNeuron numberT subjectsLower neuron numberGlobus pallidus pars externaParvalbumin-positive interneuronsTotal neuron numberUnbiased stereological techniquesChildhood neuropsychiatric disordersBasal ganglia tissueGABAergic neuronsGPi neuronsBasal gangliaCortico-striatoGlobus pallidusProtein parvalbuminThalamic circuitryGanglion tissueVocal ticsNormal controlsPutamen volumePars externaImaging studies