2017
MEF2C transcription factor is associated with the genetic and epigenetic risk architecture of schizophrenia and improves cognition in mice
Mitchell A, Javidfar B, Pothula V, Ibi D, Shen E, Peter C, Bicks L, Fehr T, Jiang Y, Brennand K, Neve R, Gonzalez-Maeso J, Akbarian S. MEF2C transcription factor is associated with the genetic and epigenetic risk architecture of schizophrenia and improves cognition in mice. Molecular Psychiatry 2017, 23: 123-132. PMID: 28115742, PMCID: PMC5966823, DOI: 10.1038/mp.2016.254.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainChromatin ImmunoprecipitationCognition DisordersComputational BiologyDisease Models, AnimalEpigenomicsGene Expression RegulationGreen Fluorescent ProteinsHistonesMEF2 Transcription FactorsMiceMice, Inbred C57BLMice, KnockoutNerve Tissue ProteinsNeuronsPolymorphism, Single NucleotideSchizophreniaTransduction, GeneticConceptsTherapeutic potentialPrefrontal projection neuronsNeuron-specific promoterUnexplored therapeutic potentialProjection neuronsDrug challengeDisease casesRelated disordersRisk architecturePrefrontal cortexSchizophreniaSingle nucleotide polymorphismsCognitive performancePsychiatric Genomics ConsortiumNeuronal genomeH3K4 hypermethylationRisk lociCognitive enhancement
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
2014
Roles of Heat Shock Factor 1 in Neuronal Response to Fetal Environmental Risks and Its Relevance to Brain Disorders
Hashimoto-Torii K, Torii M, Fujimoto M, Nakai A, Fatimy R, Mezger V, Ju MJ, Ishii S, Chao SH, Brennand KJ, Gage FH, Rakic P. Roles of Heat Shock Factor 1 in Neuronal Response to Fetal Environmental Risks and Its Relevance to Brain Disorders. Neuron 2014, 82: 560-572. PMID: 24726381, PMCID: PMC4051437, DOI: 10.1016/j.neuron.2014.03.002.Peer-Reviewed Original ResearchConceptsCerebral cortical cellsHuman neural progenitor cellsNeural progenitor cellsHeat shock factor 1Maternal seizuresSeizure susceptibilityPrenatal exposureNeuropsychiatric dysfunctionShock factor 1Neuronal responsesBrain cellsSchizophrenia patientsBrain disordersLate onsetMouse cortexStructural abnormalitiesNeuropsychiatric disordersHSF1 deficiencyExposure of embryosProgenitor cellsSubthreshold levelsFactor 1Induced pluripotent stem cellsEnvironmental insultsCortical cells