2025
Targeted analysis of dyslexia-associated regions on chromosomes 6, 12 and 15 in large multigenerational cohorts
Chapman N, Navas P, Dorschner M, Mehaffey M, Wigg K, Price K, Naumova O, Kerr E, Guger S, Lovett M, Grigorenko E, Berninger V, Barr C, Wijsman E, Raskind W. Targeted analysis of dyslexia-associated regions on chromosomes 6, 12 and 15 in large multigenerational cohorts. PLOS ONE 2025, 20: e0324006. PMID: 40424442, PMCID: PMC12112411, DOI: 10.1371/journal.pone.0324006.Peer-Reviewed Original ResearchConceptsEvidence of associationLarge-scale sequencing studiesCis-acting regulatory regionsGenome-wide association studiesAggregating rare variantsRare exonic variantsDetected significant evidenceSingle nucleotide polymorphismsGenomic variationDeleterious variantsAssociated with reduced performanceAssociation studiesLarge-effectRegulatory elementsTranscriptional regulationRegulatory regionsQuantitative phenotypesCandidate genesExonic variantsChromosome 6Sequencing studiesSingle variantsCoding exonsMultiple traitsGenetic basisMutant prion protein enhances NMDA receptor activity, activates PKC, and triggers rapid excitotoxicity in mice
Lin J, Callender J, Mayfield J, McClatchy D, Ojeda-Juárez D, Pourhamzeh M, Soldau K, Kurt T, Danque G, Khuu H, Ronson J, Pizzo D, Du Y, Gruber M, Sevillano A, Wang J, Orrú C, Chen J, Funk G, Aguilar-Calvo P, Aulston B, Roy S, Rho J, Bui J, Newton A, Lipton S, Caughey B, Patrick G, Doré K, Yates J, Sigurdson C. Mutant prion protein enhances NMDA receptor activity, activates PKC, and triggers rapid excitotoxicity in mice. Journal Of Clinical Investigation 2025, 135: e186432. PMID: 40185484, PMCID: PMC12077891, DOI: 10.1172/jci186432.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalciumGene Knock-In TechniquesHippocampusMiceMice, TransgenicMutationPrion ProteinsProtein Kinase CPrPC ProteinsPyramidal CellsReceptors, N-Methyl-D-AspartateConceptsN-methyl-D-aspartate receptorsProtein kinase CAmino terminusPrion proteinN-methyl-D-aspartateMutant prion proteinNMDA receptor activationN-linked glycosylation sitesExcitatory-inhibitory imbalanceHippocampal pyramidal neuronsDownstream signaling eventsActivate protein kinase CNMDAR channelsNeuronal hyperexcitabilityFunctional motifsGlutamate receptorsCalcium influxPhosphoproteomic analysisPyramidal neuronsGlycosylation sitesSignaling eventsReceptor activationPrion-infected miceDendritic beadingSynapse lossLong-Term Safety and Efficacy of Esmethadone in Patients With Major Depressive Disorder: Findings From a 12-Month Open-Label Study.
Fava M, Pani L, De Martin S, Cutler A, Gorodetzky C, Vocci F, Sapienza F, Kosten T, Kröger C, Champasa P, Guidetti C, Comai S, Mattarei A, Folli F, Bushnell D, Traversa S, Inturrisi C, Manfredi P, Pappagallo M. Long-Term Safety and Efficacy of Esmethadone in Patients With Major Depressive Disorder: Findings From a 12-Month Open-Label Study. The Journal Of Clinical Psychiatry 2025, 86 PMID: 39999772, DOI: 10.4088/jcp.24m15438.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntidepressive AgentsDepressive Disorder, MajorDouble-Blind MethodFemaleHumansMaleMiddle AgedReceptors, N-Methyl-D-AspartateTreatment OutcomeConceptsDepressive disorderColumbia-Suicide Severity Rating ScaleOpen-label studyDSM-5</i> criteriaFull analysis setMajor depressive disorderMeasures of depressionSeverity Rating ScaleSexual adverse eventsAntidepressant efficacyTreatment-emergent adverse eventsPostbaseline efficacy assessmentAdverse eventsSuicide attemptsUncompetitive antagonistCognitive functionSafety populationEfficacy assessmentRating ScaleEfficacy measuresMDDDouble-blind studyEmergent adverse eventsLong-term treatmentTreatment-related treatment-emergent adverse events
2024
Role of cholesterol in modulating brain hyperexcitability
Wheless J, Rho J. Role of cholesterol in modulating brain hyperexcitability. Epilepsia 2024, 66: 33-46. PMID: 39487852, PMCID: PMC11742637, DOI: 10.1111/epi.18174.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainCholesterolCholesterol 24-HydroxylaseEpilepsyHumansReceptors, N-Methyl-D-AspartateConceptsN-methyl-D-aspartateMultiple animal modelsPositive allosteric modulatorsEpileptic encephalopathyModulation of N-methyl-D-aspartateOverstimulation of NMDA receptorsAnimal models of epilepsyExcitatory amino acid transporter 2Amino acid transporter 2Models of epilepsyMetabolism of brain cholesterolBlood-brain barrierCentral nervous systemActive metabolismBrain cholesterolNMDA receptorsNeuronal hyperexcitabilityPrimary metabolic enzymesGlutamate releaseNeuronal excitabilityMechanism of actionExtracellular glutamateGlutamate reuptakeBrain hyperexcitabilityCholesterol 24-hydroxylaseHebbian instruction of axonal connectivity by endogenous correlated spontaneous activity
Matsumoto N, Barson D, Liang L, Crair M. Hebbian instruction of axonal connectivity by endogenous correlated spontaneous activity. Science 2024, 385: eadh7814-eadh7814. PMID: 39146415, PMCID: PMC12148345, DOI: 10.1126/science.adh7814.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsMiceMice, Mutant StrainsNeuronal PlasticityReceptors, N-Methyl-D-AspartateRetinal Ganglion CellsSuperior ColliculiConceptsSpontaneous activitySpontaneous retinal wavesAxonal connectionsPatterns of correlated activityNeonatal miceEvidence in vivoRetinal wavesPostsynaptic neuronsNeuronal activityIn vivoAxonal arborsAxonal processesAxonsRetinocollicular axonsNeural connectionsIndividual axonsMorphological changesSubcellular precisionEndogenous pattern
2023
Restorative effect of NitroSynapsin on synaptic plasticity in an animal model of depression
Tse W, Pochwat B, Szewczyk B, Misztak P, Bobula B, Tokarski K, Worch R, Czarnota-Bojarska M, Lipton S, Zaręba-Kozioł M, Bijata M, Wlodarczyk J. Restorative effect of NitroSynapsin on synaptic plasticity in an animal model of depression. Neuropharmacology 2023, 241: 109729. PMID: 37797736, DOI: 10.1016/j.neuropharm.2023.109729.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntidepressive AgentsDepressionDepressive Disorder, MajorDisease Models, AnimalMaleMiceMice, Inbred C57BLNeuronal PlasticityPrefrontal CortexReceptors, N-Methyl-D-AspartateConceptsMedial prefrontal cortexLong-term potentiationChronic restraint stress mouse modelSynaptic plasticityN-methyl-D-aspartate receptor antagonistRestraint stress mouse modelMale C57BL/6J miceAntidepressant-like activityTail suspension testStress mouse modelFunctional synaptic plasticityMajor depressive disorderAntidepressant potentialPharmacological treatmentPsychotomimetic effectsReceptor antagonistC57BL/6J miceDepressive behaviorSucrose preferenceDepressive disorderNitroSynapsinMouse modelSuspension testBehavioral disturbancesCerebrocortical neuronsKetamine and rapid antidepressant action: new treatments and novel synaptic signaling mechanisms
Krystal J, Kavalali E, Monteggia L. Ketamine and rapid antidepressant action: new treatments and novel synaptic signaling mechanisms. Neuropsychopharmacology 2023, 49: 41-50. PMID: 37488280, PMCID: PMC10700627, DOI: 10.1038/s41386-023-01629-w.Peer-Reviewed Original ResearchMeSH KeywordsAntidepressive AgentsDepressionDepressive Disorder, Treatment-ResistantHumansKetamineReceptors, N-Methyl-D-AspartateSynapsesConceptsMood disordersEffective treatmentN-methyl-D-aspartate receptorsGlutamatergic N-methyl-D-aspartate receptorRapid antidepressant effectsTreatment-resistant depressionKey clinical aspectsRapid antidepressant actionsNovel effective treatmentsSynaptic signaling mechanismsMore effective treatmentsSynaptic plasticity mechanismsOpen channel blockerAntidepressant actionAntidepressant effectsKetamine effectsChannel blockersClinical aspectsClinical practiceNew treatmentsNeuropsychiatric disordersCircuit mechanismsDisordersTreatmentKetamine
2022
Journal Club: Neurofilament Light Chain Levels in Anti-NMDAR Encephalitis and Primary Psychiatric Psychosis
Deerhake M, Giarraputo J, Gupta M, Eckstein C. Journal Club: Neurofilament Light Chain Levels in Anti-NMDAR Encephalitis and Primary Psychiatric Psychosis. Neurology 2022, 99: 854-857. PMID: 36038273, PMCID: PMC9651450, DOI: 10.1212/wnl.0000000000201235.Peer-Reviewed Original ResearchMeSH KeywordsAnti-N-Methyl-D-Aspartate Receptor EncephalitisHumansIntermediate FilamentsPsychotic DisordersReceptors, N-Methyl-D-AspartateConceptsNMDA receptor encephalitisAntibody testingNeurofilament light chain levelsAutoimmune brain disordersAnti-NMDAR encephalitisSubset of patientsPrimary psychiatric disordersLight chain levelsReceptor encephalitisLumbar punctureNMDA receptorsSerum testPsychiatric disordersBrain disordersClinical settingEncephalitisDisordersPatientsPuncturePsychosisCSFChain levelAntibodiesReceptorsPositive modulation of N-methyl-D-aspartate receptors in the mPFC reduces the spontaneous recovery of fear
Lee B, Pothula S, Wu M, Kang H, Girgenti MJ, Picciotto MR, DiLeone RJ, Taylor JR, Duman RS. Positive modulation of N-methyl-D-aspartate receptors in the mPFC reduces the spontaneous recovery of fear. Molecular Psychiatry 2022, 27: 2580-2589. PMID: 35418600, PMCID: PMC9135632, DOI: 10.1038/s41380-022-01498-7.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsExtinction, PsychologicalFearMaleMicePrefrontal CortexRatsRats, Sprague-DawleyReceptors, N-Methyl-D-AspartateConceptsPosttraumatic stress disorderFear extinctionInfralimbic medial prefrontal cortexFear conditioning modelEnhanced fear extinctionFear-based behaviorsProlonged stress modelMedial prefrontal cortexSpontaneous recoveryIL-mPFCPTSD modelPTSD treatmentStress disorderPrefrontal cortexSPS modelN-methyl-D-aspartate receptor modulatorsBrain-derived neurotrophic factorN-methyl-D-aspartate receptorsBehavioral effectsIncreased attentionMPFCPreclinical findingsPyramidal neuronsNeurotrophic factorMale miceValidation of ketamine as a pharmacological model of thalamic dysconnectivity across the illness course of schizophrenia
Abram SV, Roach BJ, Fryer SL, Calhoun VD, Preda A, van Erp TGM, Bustillo JR, Lim KO, Loewy RL, Stuart BK, Krystal JH, Ford JM, Mathalon DH. Validation of ketamine as a pharmacological model of thalamic dysconnectivity across the illness course of schizophrenia. Molecular Psychiatry 2022, 27: 2448-2456. PMID: 35422467, PMCID: PMC9135621, DOI: 10.1038/s41380-022-01502-0.Peer-Reviewed Original ResearchMeSH KeywordsGlutamatesHallucinationsHumansKetamineLamotrigineMagnetic Resonance ImagingReceptors, N-Methyl-D-AspartateSchizophreniaConceptsThalamic dysconnectivityHealthy controlsDysconnectivity patternsIllness courseHealthy volunteersN-methyl-D-aspartate (NMDA) receptor hypofunctionResting-state functional magnetic resonance imaging studyHallucination severityEarly illness schizophreniaExcess glutamate releaseGlutamate release inhibitorNMDAR antagonist ketaminePlacebo-controlled studyMagnetic resonance imaging studySub-anesthetic dosesSchizophrenia-like symptomsResonance imaging studyFunctional magnetic resonance imaging studyKetamine infusionGlutamate releaseNMDAR hypofunctionReceptor hypofunctionKetamine effectsThalamic connectivityRelease inhibitorComparison of three novel radiotracers for GluN2B-containing NMDA receptors in non-human primates: (R)-[11C]NR2B-Me, (R)-[18F]of-Me-NB1, and (S)-[18F]of-NB1
Smart K, Zheng MQ, Ahmed H, Fang H, Xu Y, Cai L, Holden D, Kapinos M, Haider A, Felchner Z, Ropchan JR, Tamagnan G, Innis RB, Pike VW, Ametamey SM, Huang Y, Carson RE. Comparison of three novel radiotracers for GluN2B-containing NMDA receptors in non-human primates: (R)-[11C]NR2B-Me, (R)-[18F]of-Me-NB1, and (S)-[18F]of-NB1. Cerebrovascular And Brain Metabolism Reviews 2022, 42: 1398-1409. PMID: 35209743, PMCID: PMC9274863, DOI: 10.1177/0271678x221084416.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainMacaca mulattaPositron-Emission TomographyRadiopharmaceuticalsReceptors, N-Methyl-D-AspartateConceptsNon-human primatesNMDA receptorsML/GluN2B-containing NMDA receptorsFree fractionRegional non-displaceable binding potentialsNon-displaceable binding potentialGood brain uptakeAdult rhesus macaquesBrain uptakeOne-tissue compartment modelTime-activity curvesNovel radiotracersGray matterNeuropsychiatric disordersSelective radiotracerDisplaceable bindingRhesus macaquesTissue distributionAcceptable profilePotential translationRadiotracerCerebellumFurther investigationReceptorsCharacterization in nonhuman primates of (R)-[18F]OF-Me-NB1 and (S)-[18F]OF-Me-NB1 for imaging the GluN2B subunits of the NMDA receptor
Zheng M, Ahmed H, Smart K, Xu Y, Holden D, Kapinos M, Felchner Z, Haider A, Tamagnan G, Carson RE, Huang Y, Ametamey SM. Characterization in nonhuman primates of (R)-[18F]OF-Me-NB1 and (S)-[18F]OF-Me-NB1 for imaging the GluN2B subunits of the NMDA receptor. European Journal Of Nuclear Medicine And Molecular Imaging 2022, 49: 2153-2162. PMID: 35107627, PMCID: PMC9165293, DOI: 10.1007/s00259-022-05698-9.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainHumansMacaca mulattaPositron-Emission TomographyRadiochemistryRadiopharmaceuticalsReceptors, N-Methyl-D-Aspartate
2021
First-in-Humans Brain PET Imaging of the GluN2B-Containing N-methyl-d-aspartate Receptor with (R)-11C-Me-NB1
Rischka L, Vraka C, Pichler V, Rasul S, Nics L, Gryglewski G, Handschuh P, Murgaš M, Godbersen GM, Silberbauer LR, Unterholzner J, Wotawa C, Haider A, Ahmed H, Schibli R, Mindt T, Mitterhauser M, Wadsak W, Hahn A, Lanzenberger R, Hacker M, Ametamey SM. First-in-Humans Brain PET Imaging of the GluN2B-Containing N-methyl-d-aspartate Receptor with (R)-11C-Me-NB1. Journal Of Nuclear Medicine 2021, 63: 936-941. PMID: 34620732, PMCID: PMC9157734, DOI: 10.2967/jnumed.121.262427.Peer-Reviewed Original ResearchN-methyl-D-aspartate receptor antibody and the choroid plexus in schizophrenia patients with tardive dyskinesia
Li N, Huang J, Zhang P, Tong J, Chen S, Cui Y, Tan S, Wang Z, Tian B, Li CR, Hong LE, Tian L, Tan Y. N-methyl-D-aspartate receptor antibody and the choroid plexus in schizophrenia patients with tardive dyskinesia. Journal Of Psychiatric Research 2021, 142: 290-298. PMID: 34411812, DOI: 10.1016/j.jpsychires.2021.08.010.Peer-Reviewed Original ResearchMeSH KeywordsAutoantibodiesChoroid PlexusHumansReceptors, N-Methyl-D-AspartateSchizophreniaTardive DyskinesiaConceptsNMDAR antibody levelsNeuronal N-methyl-D-aspartate receptorAbnormal Involuntary Movement ScaleTardive dyskinesiaAntibody levelsCentral nervous systemChoroid plexusAIMS scoresN-methyl-D-aspartate receptor antibodiesSchizophrenia patientsN-methyl-D-aspartate receptorsOrofacial tardive dyskinesiaCP volumeNegative Syndrome ScaleEnzyme-linked immunosorbentNMDAR antibodiesAutoimmune abnormalitiesImmune disturbancesReceptor antibodiesHealthy controlsImmune barrierMovement ScaleNervous systemNTD groupSyndrome ScaleRegulation of the NMDA receptor by its cytoplasmic domains: (How) is the tail wagging the dog?
Ishchenko Y, Carrizales MG, Koleske AJ. Regulation of the NMDA receptor by its cytoplasmic domains: (How) is the tail wagging the dog? Neuropharmacology 2021, 195: 108634. PMID: 34097949, PMCID: PMC8410658, DOI: 10.1016/j.neuropharm.2021.108634.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCytoplasmNeuronal PlasticityReceptors, N-Methyl-D-AspartateSignal TransductionSynaptic TransmissionConceptsCarboxyl-terminal domainN-methyl-D-aspartate receptorsUnique modular architectureIntracellular C-tailAmino acid sequenceDocking motifAttention deficit hyperactivity disorderKnown proteinsCytoplasmic domainC-tailTerminal domainSequence homologyAcid sequenceSynapse developmentSynaptic targetingCovalent modificationGenetic variantsGlutamate receptor subunitsAllosteric modulationImportant functionsReceptor subunitsIntellectual disabilityMetabotropic signalingSubunitsProteinAsynchronous release sites align with NMDA receptors in mouse hippocampal synapses
Li S, Raychaudhuri S, Lee SA, Brockmann MM, Wang J, Kusick G, Prater C, Syed S, Falahati H, Ramos R, Bartol TM, Hosy E, Watanabe S. Asynchronous release sites align with NMDA receptors in mouse hippocampal synapses. Nature Communications 2021, 12: 677. PMID: 33514725, PMCID: PMC7846561, DOI: 10.1038/s41467-021-21004-x.Peer-Reviewed Original Researchα-Synuclein Oligomers Induce Glutamate Release from Astrocytes and Excessive Extrasynaptic NMDAR Activity in Neurons, Thus Contributing to Synapse Loss
Trudler D, Sanz-Blasco S, Eisele Y, Ghatak S, Bodhinathan K, Akhtar M, Lynch W, Piña-Crespo J, Talantova M, Kelly J, Lipton S. α-Synuclein Oligomers Induce Glutamate Release from Astrocytes and Excessive Extrasynaptic NMDAR Activity in Neurons, Thus Contributing to Synapse Loss. Journal Of Neuroscience 2021, 41: 2264-2273. PMID: 33483428, PMCID: PMC8018774, DOI: 10.1523/jneurosci.1871-20.2020.Peer-Reviewed Original ResearchConceptsLewy body dementiaExtrasynaptic NMDA receptorsSynaptic damageParkinson's diseaseNeuronal lossLewy bodiesNMDAR activityDisease progressionΑSyn oligomersPotential disease-modifying interventionsNeurodegenerative diseasesΑ-synucleinExtrasynaptic NMDAR activitySynaptic NMDAR activityDisease-modifying interventionsPatch-clamp recordingsMajor neuropathological characteristicsSynaptic lossAstrocytic glutamateGlutamate releaseSynapse lossSpine lossExtrasynaptic NMDARsFemale miceHippocampal slices
2020
Positive modulation of NMDA receptors by AGN-241751 exerts rapid antidepressant-like effects via excitatory neurons
Pothula S, Liu RJ, Wu M, Sliby AN, Picciotto MR, Banerjee P, Duman RS. Positive modulation of NMDA receptors by AGN-241751 exerts rapid antidepressant-like effects via excitatory neurons. Neuropsychopharmacology 2020, 46: 799-808. PMID: 33059355, PMCID: PMC8027594, DOI: 10.1038/s41386-020-00882-7.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntidepressive AgentsDepressive Disorder, MajorMiceNeuronsPrefrontal CortexReceptors, N-Methyl-D-AspartateConceptsAntidepressant-like effectsMedial prefrontal cortexRapid antidepressant-like effectsGluN2B-containing NMDARsPositive allosteric modulatorsNMDAR positive allosteric modulatorExcitatory neuronsExerts antidepressant-like effectsAntidepressant-like behavioral effectsPrefrontal cortexBehavioral effectsAkt/mTORAntidepressant-like actionChronic unpredictable stressNMDA receptor activityRecent preclinical studiesMajor depressive disorderSpecific knockdownParvalbumin inhibitory neuronsCellular triggersSynaptic proteinsGlutamatergic systemNMDAR activityClinical trialsDepressive disorderA circuit mechanism for decision-making biases and NMDA receptor hypofunction
Cavanagh SE, Lam NH, Murray JD, Hunt LT, Kennerley SW. A circuit mechanism for decision-making biases and NMDA receptor hypofunction. ELife 2020, 9: e53664. PMID: 32988455, PMCID: PMC7524553, DOI: 10.7554/elife.53664.Peer-Reviewed Original ResearchConceptsNMDA-R hypofunctionCortical excitation/inhibition balanceExcitation/inhibition balanceNMDA receptor hypofunctionNMDA receptor antagonismNMDA-R antagonist ketamineCircuit-level mechanismsPotential neural mechanismsNeuropsychiatric symptomsReceptor hypofunctionReceptor antagonismInhibition balanceExcitatory neuronsInhibitory neuronsPharmacological modelPharmacological manipulationNeuropsychiatric disordersCircuit mechanismsHypofunctionVariable evidenceNeural mechanismsKetamineNeuronsBehavioral psychophysicsPossible effectsNMDAR-Dependent Emergence of Behavioral Representation in Primary Visual Cortex
Puścian A, Benisty H, Higley MJ. NMDAR-Dependent Emergence of Behavioral Representation in Primary Visual Cortex. Cell Reports 2020, 32: 107970. PMID: 32726633, PMCID: PMC7431963, DOI: 10.1016/j.celrep.2020.107970.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsFemaleGlutamic AcidInterneuronsMaleMiceMice, Inbred C57BLNeuronal PlasticityNeuronsParvalbuminsPyramidal CellsReceptors, N-Methyl-D-AspartateVisual CortexConceptsPrimary visual cortexVisual cortexNMDA-type glutamate receptorsNeocortical sensory areasFunctional plasticityConsiderable functional plasticityPyramidal cellsGlutamate receptorsCell-autonomous expressionV1 neuronsVisual task performanceSensory areasExperience-dependent emergenceCortical networksBehavioral outputCortexVisual inputBehavioral demandsMiceNeuronsReceptors
This site is protected by hCaptcha and its Privacy Policy and Terms of Service apply