2022
Sexual dimorphism in a neuronal mechanism of spinal hyperexcitability across rodent and human models of pathological pain
Dedek A, Xu J, Lorenzo LÉ, Godin AG, Kandegedara CM, Glavina G, Landrigan JA, Lombroso PJ, De Koninck Y, Tsai EC, Hildebrand ME. Sexual dimorphism in a neuronal mechanism of spinal hyperexcitability across rodent and human models of pathological pain. Brain 2022, 145: 1124-1138. PMID: 35323848, PMCID: PMC9050559, DOI: 10.1093/brain/awab408.Peer-Reviewed Original ResearchConceptsBrain-derived neurotrophic factorSuperficial dorsal horn neuronsDorsal horn neuronsFemale ratsNeurotrophic factorNeuronal mechanismsCentral neuronal mechanismsSpinal nociceptive circuitsSpinal pain processingSuperficial dorsal hornChronic pain syndromeLamina I neuronsPreclinical pain modelsHuman organ donorsSynaptic NMDAR responsesNMDAR potentiationSpinal hyperexcitabilityInflammatory painNociceptive circuitsPain syndromeTactile allodyniaDorsal hornPain modelPathological painLaminae I
2020
Antibodies From Children With PANDAS Bind Specifically to Striatal Cholinergic Interneurons and Alter Their Activity
Xu J, Liu RJ, Fahey S, Frick L, Leckman J, Vaccarino F, Duman RS, Williams K, Swedo S, Pittenger C. Antibodies From Children With PANDAS Bind Specifically to Striatal Cholinergic Interneurons and Alter Their Activity. American Journal Of Psychiatry 2020, 178: 48-64. PMID: 32539528, PMCID: PMC8573771, DOI: 10.1176/appi.ajp.2020.19070698.Peer-Reviewed Original ResearchConceptsStriatal cholinergic interneuronsCholinergic interneuronsMouse brain slicesObsessive-compulsive disorderControl subjectsBrain slicesPediatric autoimmune neuropsychiatric disordersIntravenous immunoglobulin treatmentAutoimmune neuropsychiatric disordersAcute mouse brain slicesParvalbumin-expressing GABAergic interneuronsPediatric obsessive-compulsive disorderBrain antigensImmunoglobulin treatmentBaseline serumStreptococcal infectionCritical cellular targetsSymptom improvementGABAergic interneuronsInduced autoimmunityIgG antibodiesMouse slicesIndependent cohortBehavioral pathologyNeuron typesInhibition of striatal-enriched protein tyrosine phosphatase (STEP) activity reverses behavioral deficits in a rodent model of autism
Chatterjee M, Singh P, Xu J, Lombroso PJ, Kurup PK. Inhibition of striatal-enriched protein tyrosine phosphatase (STEP) activity reverses behavioral deficits in a rodent model of autism. Behavioural Brain Research 2020, 391: 112713. PMID: 32461127, PMCID: PMC7346720, DOI: 10.1016/j.bbr.2020.112713.Peer-Reviewed Original ResearchAnimalsAutism Spectrum DisorderAutistic DisorderBehavior, AnimalDisease Models, AnimalExploratory BehaviorFemaleInhibition, PsychologicalMaleMiceMice, Inbred C57BLNeuronal PlasticityPrefrontal CortexPregnancyPrenatal Exposure Delayed EffectsProtein Tyrosine PhosphatasesProtein Tyrosine Phosphatases, Non-ReceptorSocial BehaviorStereotyped BehaviorValproic Acid
2019
Loss of STEP61 couples disinhibition to N-methyl-d-aspartate receptor potentiation in rodent and human spinal pain processing
Dedek A, Xu J, Kandegedara CM, Lorenzo LÉ, Godin AG, De Koninck Y, Lombroso PJ, Tsai EC, Hildebrand ME. Loss of STEP61 couples disinhibition to N-methyl-d-aspartate receptor potentiation in rodent and human spinal pain processing. Brain 2019, 142: 1535-1546. PMID: 31135041, PMCID: PMC6536915, DOI: 10.1093/brain/awz105.Peer-Reviewed Original ResearchConceptsN-methyl-D-aspartate receptorsLaminae INMDAR responsesDorsal horn synapsesSpinal pain processingNerve injury modelSpinal dorsal hornSynaptic NMDAR responsesTyrosine phosphatase STEP61Loss of inhibitionBehavioral hypersensitivityInflammatory painNeuropathic painDorsal hornPain statesPathological painPain targetsChronic painPain processingInjury modelAssociated downregulationRodent modelsReceptor potentiationPainSTEP61 activity
2018
Striatal Signaling Regulated by the H3R Histamine Receptor in a Mouse Model of tic Pathophysiology
Rapanelli M, Frick L, Jindachomthong K, Xu J, Ohtsu H, Nairn A, Pittenger C. Striatal Signaling Regulated by the H3R Histamine Receptor in a Mouse Model of tic Pathophysiology. Neuroscience 2018, 392: 172-179. PMID: 30278251, PMCID: PMC6204318, DOI: 10.1016/j.neuroscience.2018.09.035.Peer-Reviewed Original ResearchConceptsHDC-KO miceMitogen-activated protein kinaseHistamine receptorsWT animalsDorsal striatumH3R activationTic-like movementsStriatonigral medium spiny neuronsAkt phosphorylationMedium spiny neuronsWild-type miceRare genetic causeHistamine dysregulationAgonist treatmentKO miceSpiny neuronsTic disordersTic pathophysiologyStriatal signalingMouse modelNeuropsychiatric diseasesKO modelRepetitive movementsStriatumMice
2016
Inhibition of STEP61 ameliorates deficits in mouse and hiPSC-based schizophrenia models
Xu J, Hartley BJ, Kurup P, Phillips A, Topol A, Xu M, Ononenyi C, Foscue E, Ho SM, Baguley TD, Carty N, Barros CS, Müller U, Gupta S, Gochman P, Rapoport J, Ellman JA, Pittenger C, Aronow B, Nairn AC, Nestor MW, Lombroso PJ, Brennand KJ. Inhibition of STEP61 ameliorates deficits in mouse and hiPSC-based schizophrenia models. Molecular Psychiatry 2016, 23: 271-281. PMID: 27752082, PMCID: PMC5395367, DOI: 10.1038/mp.2016.163.Peer-Reviewed Original ResearchConceptsBrain-specific tyrosine phosphataseDephosphorylation of GluN2BExtracellular signal-regulated kinase 1/2Signal-regulated kinase 1/2Glutamate receptor internalizationPluripotent stem cellsKnockout mouse modelTyrosine phosphataseMouse modelKinase 1/2Receptor internalizationImportant regulatorGenetic reductionLoss of NMDARsStem cellsN-methyl DPharmacological inhibitionProtein levelsSynaptic functionSTEP61Patient cohortForebrain neuronsBehavioral deficitsExcitatory neuronsSchizophrenia model
2015
Down‐regulation of BDNF in cell and animal models increases striatal‐enriched protein tyrosine phosphatase 61 (STEP61) levels
Xu J, Kurup P, Azkona G, Baguley TD, Saavedra A, Nairn AC, Ellman JA, Pérez-Navarro E, Lombroso PJ. Down‐regulation of BDNF in cell and animal models increases striatal‐enriched protein tyrosine phosphatase 61 (STEP61) levels. Journal Of Neurochemistry 2015, 136: 285-294. PMID: 26316048, PMCID: PMC4769989, DOI: 10.1111/jnc.13295.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBenzothiepinsBrainBrain-Derived Neurotrophic FactorCells, CulturedCysteine Proteinase InhibitorsDown-RegulationEmbryo, MammalianFemaleFlavonesLeupeptinsMaleMiceMice, Inbred C57BLMice, TransgenicMotor ActivityNeuronsProtein Tyrosine PhosphatasesRatsRats, Sprague-DawleyRNA, Small InterferingTime FactorsConceptsBrain-derived neurotrophic factorNormal cognitive functionSynaptic strengtheningStriatal-enriched protein tyrosine phosphataseBDNF expressionBDNF knockdownCortical culturesRegulation of BDNFN-methyl-D-aspartate receptor functionNeuropsychiatric disordersCognitive functionBetter therapeutic strategiesMouse frontal cortexNMDA receptor subunit GluN2BSTEP61 levelsHyperlocomotor activityMotor abnormalitiesNeurotrophic factorNMDA receptorsFrontal cortexKinase B signalingTherapeutic strategiesAgonists resultsAnimal modelsCultured neurons