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
2016
Potentiation of Synaptic GluN2B NMDAR Currents by Fyn Kinase Is Gated through BDNF-Mediated Disinhibition in Spinal Pain Processing
Hildebrand ME, Xu J, Dedek A, Li Y, Sengar AS, Beggs S, Lombroso PJ, Salter MW. Potentiation of Synaptic GluN2B NMDAR Currents by Fyn Kinase Is Gated through BDNF-Mediated Disinhibition in Spinal Pain Processing. Cell Reports 2016, 17: 2753-2765. PMID: 27926876, DOI: 10.1016/j.celrep.2016.11.024.Peer-Reviewed Original ResearchConceptsBrain-derived neurotrophic factorN-methyl-D-aspartate receptorsLaminae INeurotrophin brain-derived neurotrophic factorPeripheral nerve injury modelSynaptic N-methyl-D-aspartate receptorsBDNF-TrkB signalingSpinal pain processingNerve injury modelChronic pain statesActivation of TrkBNMDAR dysregulationNMDAR potentiationPain amplificationPain hypersensitivityNeuropathic painPain statesPain processingNeurotrophic factorSpinal neuronsSynaptic excitationSynaptic inhibitionNMDAR currentsInjury modelPotentiation
2015
Inhibition of the tyrosine phosphatase STEP61 restores BDNF expression and reverses motor and cognitive deficits in phencyclidine-treated mice
Xu J, Kurup P, Baguley TD, Foscue E, Ellman JA, Nairn AC, Lombroso PJ. Inhibition of the tyrosine phosphatase STEP61 restores BDNF expression and reverses motor and cognitive deficits in phencyclidine-treated mice. Cellular And Molecular Life Sciences 2015, 73: 1503-1514. PMID: 26450419, PMCID: PMC4801664, DOI: 10.1007/s00018-015-2057-1.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBenzothiepinsBrain-Derived Neurotrophic FactorCells, CulturedCognition DisordersCREB-Binding ProteinDown-RegulationMaleMiceMice, Inbred C57BLMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Motor ActivityNeuronsPhencyclidinePhosphorylationProtein Tyrosine PhosphatasesReceptors, N-Methyl-D-AspartateRNA InterferenceUbiquitinationConceptsBrain-derived neurotrophic factorBDNF expressionProtein tyrosine Phosphatase 61Cognitive deficitsPCP-induced reductionPCP-treated micePhencyclidine-treated micePCP-induced increasePCP-induced hyperlocomotionTyrosine phosphatase STEP61STEP61 levelsBDNF transcriptionNeurotrophic factorNMDAR antagonistsCortical culturesCortical neuronsCNS disordersSynaptic strengtheningPsychotic episodeRodent modelsBrain disordersPharmacologic inhibitionSTEP61SchizophreniaCognitive functioningDown‐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 neuronsBDNF Induces Striatal-Enriched Protein Tyrosine Phosphatase 61 Degradation Through the Proteasome
Saavedra A, Puigdellívol M, Tyebji S, Kurup P, Xu J, Ginés S, Alberch J, Lombroso PJ, Pérez-Navarro E. BDNF Induces Striatal-Enriched Protein Tyrosine Phosphatase 61 Degradation Through the Proteasome. Molecular Neurobiology 2015, 53: 4261-4273. PMID: 26223799, PMCID: PMC4738169, DOI: 10.1007/s12035-015-9335-7.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrain-Derived Neurotrophic FactorCerebral CortexExtracellular Signal-Regulated MAP KinasesHippocampusMembrane PotentialsMiceNeostriatumNerve Growth FactorNeuronsNeurotrophin 3Phospholipase C gammaPhosphorylationProteasome Endopeptidase ComplexProtein Tyrosine Phosphatases, Non-ReceptorProteolysisReceptors, N-Methyl-D-AspartateUbiquitinationConceptsBrain-derived neurotrophic factorSTEP61 levelsCortical neuronsUbiquitin-proteasome systemStriatal-enriched protein tyrosine phosphatasePrimary cortical neuronsLevels/activitiesNerve growth factorNeurotrophic factorNeurotrophin-3Cultured striatalHippocampal neuronsCell depolarizationGrowth factorERK1/2 phosphorylationNeuronsStriatalTyrosine kinasePhospholipase C-gammaC gammaDifferent mechanismsLevelsBlockadeGluN2BProtein tyrosine phosphatase