2024
Sex differences in the distribution and density of regulatory interneurons in the striatum
Van Zandt M, Flanagan D, Pittenger C. Sex differences in the distribution and density of regulatory interneurons in the striatum. Frontiers In Cellular Neuroscience 2024, 18: 1415015. PMID: 39045533, PMCID: PMC11264243, DOI: 10.3389/fncel.2024.1415015.Peer-Reviewed Original ResearchFast spiking interneuronsCholinergic interneuronsDorsal striatumSex differencesTourette syndromeVentral striatumNeuropsychiatric disordersSomatostatin expressionContext of psychopathologyHuman neuropsychiatric disordersBasal ganglia functionInvestigate sex differencesNucleus accumbensCaudate-putamenBehavioral pathologyStriatumSomatostatin-expressing interneuronsStriatal interneuronsGABAergic interneuronsMale miceStereological quantificationFemale miceInterneuronsDisordersAccumbensActivation of M4 muscarinic receptors in the striatum reduces tic‐like behaviours in two distinct murine models of Tourette syndrome
Cadeddu R, Braccagni G, Branca C, van Luik E, Pittenger C, Thomsen M, Bortolato M. Activation of M4 muscarinic receptors in the striatum reduces tic‐like behaviours in two distinct murine models of Tourette syndrome. British Journal Of Pharmacology 2024, 181: 3064-3081. PMID: 38689378, DOI: 10.1111/bph.16392.Peer-Reviewed Original ResearchPositive allosteric modulatorsD1CT-7 miceTourette syndromeMouse model of TSStriatal cholinergic interneuronsTic-like behavioursC-Fos levelsModel of TSActivate c-fosM4 muscarinic receptorsMuscarinic receptorsStriatal acetylcholineMouse modelStriatal expressionTic-likeStriatal levelsCholinergic interneuronsVU0467154Current pharmacotherapyXanomelineReceptor agonistsAllosteric modulatorsC-fosReceptor antagonistStriatum
2023
Prefrontal allopregnanolone mediates the adverse effects of acute stress in a mouse model of tic pathophysiology
Cadeddu R, Van Zandt M, Santovito L, Odeh K, Anderson C, Flanagan D, Nordkild P, Pinna G, Pittenger C, Bortolato M. Prefrontal allopregnanolone mediates the adverse effects of acute stress in a mouse model of tic pathophysiology. Neuropsychopharmacology 2023, 48: 1288-1299. PMID: 37198434, PMCID: PMC10354086, DOI: 10.1038/s41386-023-01603-6.Peer-Reviewed Original ResearchConceptsEffects of allopregnanoloneTourette syndromeCholinergic interneuronsAcute stressPrefrontal cortexPrepulse inhibitionTic pathophysiologyMouse modelAdverse effectsStriatal cholinergic interneuronsDeficient prepulse inhibitionSeverity of ticsPost-mortem studiesPharmacological antagonismPPI deficitsNeurosteroid allopregnanoloneMale miceAdministration doseAllopregnanoloneAnimal modelsBehavioral pathologySymptom severityAcute stressorYoung adulthoodAP levels
2022
White matter abnormalities in the Hdc knockout mouse, a model of tic and OCD pathophysiology
Jindachomthong K, Yang C, Huang Y, Coman D, Rapanelli M, Hyder F, Dougherty J, Frick L, Pittenger C. White matter abnormalities in the Hdc knockout mouse, a model of tic and OCD pathophysiology. Frontiers In Molecular Neuroscience 2022, 15: 1037481. PMID: 36504678, PMCID: PMC9731796, DOI: 10.3389/fnmol.2022.1037481.Peer-Reviewed Original ResearchTourette syndromeDiffusion tensor imagingDorsal striatumKnockout miceFractional anisotropyCortico-basal ganglia circuitryHDC knockout miceWhite matter abnormalitiesIntact mouse brainBiosynthesis of histamineCortical projectionsNeurochemical abnormalitiesPosterior hypothalamusKO miceVocal ticsFunctional abnormalitiesMyelin productionPathological alterationsDTI literatureOCD pathophysiologyMouse brainBrain regionsKO modelAbnormalitiesTensor imagingStudying the pathophysiology of tic disorders in animal models
Pittenger C. Studying the pathophysiology of tic disorders in animal models. International Review Of Movement Disorders 2022, 4: 39-61. DOI: 10.1016/bs.irmvd.2022.06.001.Peer-Reviewed Original Research
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 deChapter 47 Animal Models of Tourette Syndrome and Obsessive-Compulsive Disorder
Pittenger C. Chapter 47 Animal Models of Tourette Syndrome and Obsessive-Compulsive Disorder. 2015, 747-764. DOI: 10.1016/b978-0-12-405195-9.00047-0.Peer-Reviewed Original ResearchObsessive-compulsive disorderTourette syndromeAnimal modelsCortico-basal ganglia circuitryAvailable pharmacological interventionsDysregulation of dopamineValid animal modelInhibitory transmissionSensory abnormalitiesSerotonergic modulationVocal ticsPharmacological interventionsLimited efficacyPrevalent diseaseNeuropsychiatric conditionsSyndromeModels of OCDComplex disorderNeurodevelopmental syndromeDisordersPathophysiologyNeurobiological processesPredictive validitySame circuitryBehavioral manipulation
2014
Histidine Decarboxylase Deficiency Causes Tourette Syndrome: Parallel Findings in Humans and Mice
Baldan LC, Williams KA, Gallezot JD, Pogorelov V, Rapanelli M, Crowley M, Anderson GM, Loring E, Gorczyca R, Billingslea E, Wasylink S, Panza KE, Ercan-Sencicek AG, Krusong K, Leventhal BL, Ohtsu H, Bloch MH, Hughes ZA, Krystal JH, Mayes L, de Araujo I, Ding YS, State MW, Pittenger C. Histidine Decarboxylase Deficiency Causes Tourette Syndrome: Parallel Findings in Humans and Mice. Neuron 2014, 81: 77-90. PMID: 24411733, PMCID: PMC3894588, DOI: 10.1016/j.neuron.2013.10.052.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAmphetamineAnimalsBrainChildDopamine AgonistsDopamine AntagonistsExploratory BehaviorFemaleHistidine DecarboxylaseHumansMaleMaze LearningMiceMice, KnockoutMiddle AgedMutationOxazinesRacloprideRadionuclide ImagingStereotyped BehaviorTime FactorsTourette SyndromeTryptophanYoung AdultConceptsTourette syndromeHA infusionKnockout miceD2/D3 receptor bindingDecarboxylase deficiencyDopamine D2 antagonist haloperidolCortico-basal ganglia circuitsStriatal DA levelsHDC knockout miceD3 receptor bindingImmediate early gene FosD2 antagonist haloperidolRare genetic causeBiosynthesis of histamineStriatal DARare causeBasal gangliaDA levelsAntagonist haloperidolGanglia circuitsPrepulse inhibitionMiceReceptor bindingGenetic causeHistidine decarboxylase
2013
Tourette Syndrome and Tic Disorders
Williams K, Bloch M, State M, Pittenger C. Tourette Syndrome and Tic Disorders. 2013, 1048-1060. DOI: 10.1093/med/9780199934959.003.0079.Peer-Reviewed Original ResearchTourette syndromeTic disordersCortico-basal ganglia circuitryImmune-brain interactionPost-mortem findingsSubset of casesFunctional imaging studiesAttention deficit disorderObsessive-compulsive disorderVocal ticsDisorder pathophysiologySevere endImaging studiesDeficit disorderSpecific populationsDisordersSyndromeSensory phenomenaRecent findingsHeterogeneous genetic architecturePathophysiologyInterneuronsEtiologyAbnormalitiesFindings