2024
The endogenous opioid system in the medial prefrontal cortex mediates ketamine’s antidepressant-like actions
Jiang C, DiLeone R, Pittenger C, Duman R. The endogenous opioid system in the medial prefrontal cortex mediates ketamine’s antidepressant-like actions. Translational Psychiatry 2024, 14: 90. PMID: 38346984, PMCID: PMC10861497, DOI: 10.1038/s41398-024-02796-0.Peer-Reviewed Original ResearchConceptsMedial prefrontal cortexAction of ketamineEndogenous opioid systemAntidepressant-like actionOpioid systemB-endorphinKetamine treatmentAntidepressant-like actions of ketamineBehavioral actions of ketamineAntidepressant actions of ketamineBehavioral effects of ketamineSingle dose of ketamineAntidepressant-like effectsLevels of B-endorphinAcute systemic administrationEffects of ketamineDose of ketamineOpioid receptor antagonistAntidepressant actionPrefrontal cortexActivation of opioid receptorsBehavioral effectsBehavioral actionsCompetitive opioid receptor antagonistOpioid receptors
2023
Targeted and selective knockout of the TLQP-21 neuropeptide unmasks its unique role in energy homeostasis
Sahu B, Razzoli M, McGonigle S, Pallais J, Nguyen M, Sadahiro M, Jiang C, Lin W, Kelley K, Rodriguez P, Mansk R, Cero C, Caviola G, Palanza P, Rao L, Beetch M, Alejandro E, Sham Y, Frontini A, Salton S, Bartolomucci A. Targeted and selective knockout of the TLQP-21 neuropeptide unmasks its unique role in energy homeostasis. Molecular Metabolism 2023, 76: 101781. PMID: 37482186, PMCID: PMC10400922, DOI: 10.1016/j.molmet.2023.101781.Peer-Reviewed Original ResearchConceptsGenetic engineering approachesUnique metabolic phenotypeMass spectrometry identificationPrecursor geneGel digestionGenetic lossTLQP-21Cleavage siteC-terminal arginineGenesMutant sequencesSelective knockoutEssential roleBiological constraintsMetabolic phenotypeMouse linesEnergy homeostasisComposite phenotypeMutant miceValuable resourceVGF gene348. Sexual Dimorphism in the Behavioral Outcomes Following Early Life Stress
Jiang C, Pittenger C. 348. Sexual Dimorphism in the Behavioral Outcomes Following Early Life Stress. Biological Psychiatry 2023, 93: s234. DOI: 10.1016/j.biopsych.2023.02.588.Peer-Reviewed Original Research
2022
P456. The Effects of Early Life Stress on Tourette Syndrome-Relevant Pathology
Jiang C, Pittenger C. P456. The Effects of Early Life Stress on Tourette Syndrome-Relevant Pathology. Biological Psychiatry 2022, 91: s272. DOI: 10.1016/j.biopsych.2022.02.692.Peer-Reviewed Original Research
2021
An increase in VGF expression through a rapid, transcription-independent, autofeedback mechanism improves cognitive function
Lin W, Zhao Y, Li Z, Zheng S, Zou J, Warren N, Bali P, Wu J, Xing M, Jiang C, Tang Y, Salton S, Ye X. An increase in VGF expression through a rapid, transcription-independent, autofeedback mechanism improves cognitive function. Translational Psychiatry 2021, 11: 383. PMID: 34238925, PMCID: PMC8266826, DOI: 10.1038/s41398-021-01489-2.Peer-Reviewed Original ResearchConceptsDense-core vesiclesTLQP-62VGF-derived peptide TLQP-62Cognitive functionGranin familyDepression-like behaviorRelease of neuropeptidesGranin proteinsHippocampus-dependent learningCultured primary neuronsLuciferase-based reporter assayGranin family proteinsTranscription-independent inductionNeuronal activationMood disordersAutofeedback mechanismNeuronal activityPrimary neuronsVGF expressionMice exhibitMood stabilityAlzheimer's diseaseBrain tissueMRNA expressionNeurodegenerative diseases
2020
Multiscale causal networks identify VGF as a key regulator of Alzheimer’s disease
Beckmann ND, Lin WJ, Wang M, Cohain AT, Charney AW, Wang P, Ma W, Wang YC, Jiang C, Audrain M, Comella PH, Fakira AK, Hariharan SP, Belbin GM, Girdhar K, Levey AI, Seyfried NT, Dammer EB, Duong D, Lah JJ, Haure-Mirande JV, Shackleton B, Fanutza T, Blitzer R, Kenny E, Zhu J, Haroutunian V, Katsel P, Gandy S, Tu Z, Ehrlich ME, Zhang B, Salton SR, Schadt EE. Multiscale causal networks identify VGF as a key regulator of Alzheimer’s disease. Nature Communications 2020, 11: 3942. PMID: 32770063, PMCID: PMC7414858, DOI: 10.1038/s41467-020-17405-z.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAlzheimer DiseaseAmyloid beta-PeptidesAnimalsBrainDatasets as TopicDisease Models, AnimalFemaleGene Expression ProfilingGene Regulatory NetworksGenome-Wide Association StudyHumansMaleMiceMice, TransgenicNerve Growth FactorsProtein Interaction MappingProtein Interaction MapsProteomicsVGF-derived peptide TLQP-21 modulates microglial function through C3aR1 signaling pathways and reduces neuropathology in 5xFAD mice
El Gaamouch F, Audrain M, Lin WJ, Beckmann N, Jiang C, Hariharan S, Heeger PS, Schadt EE, Gandy S, Ehrlich ME, Salton SR. VGF-derived peptide TLQP-21 modulates microglial function through C3aR1 signaling pathways and reduces neuropathology in 5xFAD mice. Molecular Neurodegeneration 2020, 15: 4. PMID: 31924226, PMCID: PMC6954537, DOI: 10.1186/s13024-020-0357-x.Peer-Reviewed Original ResearchConceptsPeptide TLQP-21TLQP-21BV2 microglial cellsClinical Dementia RatingMicroglial functionAlzheimer's diseasePrimary microgliaMicroglial cellsMurine microgliaSuper agonistMurine BV2 microglial cellsAmyloid plaque densityWild-type microgliaAD-related neuropathologyAccelerating Medicines PartnershipMicroglial cell lineImplanted osmotic pumpsVGF levelsDystrophic neuritesBraak scoresHuman microgliaPlaque densityAD progressionMicroglial genesAmyloid plaquesChapter 7 Neuroprotective roles of neurotrophic growth factors in mood disorders
Jiang C, Salton S. Chapter 7 Neuroprotective roles of neurotrophic growth factors in mood disorders. 2020, 145-172. DOI: 10.1016/b978-0-12-814037-6.00010-0.Peer-Reviewed Original ResearchBrain-derived neurotrophic factorNeurotrophic growth factorsMood disordersAntidepressant efficacyDepressive behaviorGrowth factorDepression-like behaviorAntidepressant actionAntidepressant responseDendritic lengthNeuroprotective roleSpine densityNeurotrophic factorNeurotrophin actionNeuronal cytoarchitectureAnimal modelsGene polymorphismsSynaptic plasticityProtein levelsDisordersReceptorsGenetic associationEfficacySpecific mechanismsCritical role
2019
Grape‐derived polyphenols produce antidepressant effects via VGF‐ and BDNF‐dependent mechanisms
Jiang C, Sakakibara E, Lin W, Wang J, Pasinetti GM, Salton SR. Grape‐derived polyphenols produce antidepressant effects via VGF‐ and BDNF‐dependent mechanisms. Annals Of The New York Academy Of Sciences 2019, 1455: 196-205. PMID: 31074515, PMCID: PMC6834858, DOI: 10.1111/nyas.14098.Peer-Reviewed Original ResearchConceptsDepression-like behaviorAntidepressant efficacyTLQP-62VGF-derived peptide TLQP-62Stress-induced depression-like behaviorsBDNF-dependent mechanismAntidepressant-like effectsChronic variable stressGrape-derived polyphenolsAntidepressant actionAntidepressant effectsBDNF expressionNaive miceDorsal hippocampusPolyphenol preparationsFloxed miceVGF expressionPrior knockdownEfficacyVGFMiceMolecular mechanismsRecent studiesVariable stressBDNF
2018
VGF and its C-terminal peptide TLQP-62 in ventromedial prefrontal cortex regulate depression-related behaviors and the response to ketamine
Jiang C, Lin WJ, Labonté B, Tamminga CA, Turecki G, Nestler EJ, Russo SJ, Salton SR. VGF and its C-terminal peptide TLQP-62 in ventromedial prefrontal cortex regulate depression-related behaviors and the response to ketamine. Neuropsychopharmacology 2018, 44: 971-981. PMID: 30504797, PMCID: PMC6462025, DOI: 10.1038/s41386-018-0277-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntidepressive AgentsBehavior, AnimalBrain-Derived Neurotrophic FactorDepressionDepressive Disorder, MajorDisease Models, AnimalDisease SusceptibilityFemaleHumansKetamineMaleMiceMice, 129 StrainMice, Inbred C57BLMice, TransgenicNerve Growth FactorsNeuropeptidesPeptidesPrefrontal CortexStress, PsychologicalConceptsChronic restraint stressMajor depressive disorderAntidepressant efficacyAntidepressant responseVentromedial prefrontal cortexPrefrontal cortexAntidepressant drug treatmentKetamine's antidepressant efficacyAntidepressant-like effectsDepression-related behaviorsBrodmann area 25Neuropeptide precursor VGFChannel-mediated Ca2Underlying molecular pathwaysTLQP-62Vgf knockdownVGF levelsBDNF expressionMDD patientsRestraint stressDepressive disorderFunctional deficitsDrug treatmentBehavioral deficitsNucleus accumbensα1- and β3-Adrenergic Receptor–Mediated Mesolimbic Homeostatic Plasticity Confers Resilience to Social Stress in Susceptible Mice
Zhang H, Chaudhury D, Nectow AR, Friedman AK, Zhang S, Juarez B, Liu H, Pfau ML, Aleyasin H, Jiang C, Crumiller M, Calipari ES, Ku SM, Morel C, Tzavaras N, Montgomery SE, He M, Salton SR, Russo SJ, Nestler EJ, Friedman JM, Cao JL, Han MH. α1- and β3-Adrenergic Receptor–Mediated Mesolimbic Homeostatic Plasticity Confers Resilience to Social Stress in Susceptible Mice. Biological Psychiatry 2018, 85: 226-236. PMID: 30336931, PMCID: PMC6800029, DOI: 10.1016/j.biopsych.2018.08.020.Peer-Reviewed Original ResearchMeSH KeywordsAdrenergic alpha-1 Receptor AgonistsAdrenergic alpha-1 Receptor AntagonistsAdrenergic beta-3 Receptor AgonistsAdrenergic beta-3 Receptor AntagonistsAnimalsBehavior, AnimalDopaminergic NeuronsHomeostasisLocus CoeruleusMaleMiceNeural PathwaysNeuronal PlasticityReceptors, Adrenergic, alpha-1Receptors, Adrenergic, beta-3Resilience, PsychologicalStress, PsychologicalVentral Tegmental AreaConceptsSocial defeat stressDA neuronsSusceptible miceHomeostatic plasticityLocus coeruleusDefeat stressAdrenergic receptorsChronic social defeat stress (CSDS) modelSocial defeat stress modelVTA DA neuronsDepression-related behaviorsMesolimbic DA neuronsMesolimbic dopamine neuronsΒ3-adrenergic receptorMolecular profiling studiesNew molecular targetsSocial stressCircuit neuronsLC neuronsDopamine neuronsNucleus accumbensOptogenetic activationCellular hyperactivityPrecise circuitryStress resilienceRole of a VGF/BDNF/TrkB Autoregulatory Feedback Loop in Rapid-Acting Antidepressant Efficacy
Jiang C, Lin WJ, Salton SR. Role of a VGF/BDNF/TrkB Autoregulatory Feedback Loop in Rapid-Acting Antidepressant Efficacy. Journal Of Molecular Neuroscience 2018, 68: 504-509. PMID: 30022437, PMCID: PMC6338529, DOI: 10.1007/s12031-018-1124-0.Peer-Reviewed Original ResearchConceptsBrain-derived neurotrophic factorRapid-acting antidepressantsTLQP-62Antidepressant efficacyReceptor activationN-methyl-D-aspartate receptorsParticular brain-derived neurotrophic factorIsoxazolepropionic acid receptor (AMPAR) activationBDNF/TrkBDepression-like behaviorRapid antidepressant actionsIntra-hippocampal administrationAMPA receptor activationExpression of VGFChemical antidepressantsAntidepressant actionBDNF expressionSustained efficacyNeurotrophic factorNeurotrophin familySwim testVoluntary exerciseMTOR pathwayMTOR activationAntidepressants
2017
VGF function in depression and antidepressant efficacy
Jiang C, Lin WJ, Sadahiro M, Labonté B, Menard C, Pfau ML, Tamminga CA, Turecki G, Nestler EJ, Russo SJ, Salton SR. VGF function in depression and antidepressant efficacy. Molecular Psychiatry 2017, 23: 1632-1642. PMID: 29158577, PMCID: PMC5962361, DOI: 10.1038/mp.2017.233.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsAntidepressive AgentsBrain-Derived Neurotrophic FactorDepressionDepressive DisorderDown-RegulationFemaleHippocampusHumansKetamineMaleMiceMice, Inbred C57BLMiddle AgedNerve Growth FactorsNeuronsNeuropeptidesNucleus AccumbensReceptors, AMPASex FactorsSignal TransductionStress, PsychologicalTOR Serine-Threonine KinasesUp-RegulationConceptsChronic social defeat stressDepression-like behaviorBrain-derived neurotrophic factorSocial defeat stressNucleus accumbensAntidepressant efficacyAntidepressant responseDefeat stressFloxed micePro-depressant effectsRapid antidepressant efficacyBDNF/TrkBIsoxazolepropionic acid (AMPA) receptorsWild-type miceDepressed human subjectsBDNF translationTLQP-62VGF levelsAAV-CreAntidepressant behaviorNeurotrophic factorSwim testDorsal hippocampusInhibitory interneuronsVGF expressionVGF and its C-terminal peptide TLQP-62 regulate memory formation and depressive behavior via a BDNF-TrkB-dependent mechanism
Lin W, Jiang C, Sadahiro M, Bozdagi O, Vulchanova L, Russo S, Alberini C, Salton S. VGF and its C-terminal peptide TLQP-62 regulate memory formation and depressive behavior via a BDNF-TrkB-dependent mechanism. Neuropeptides 2017, 65: 129. DOI: 10.1016/j.npep.2017.02.005.Peer-Reviewed Original ResearchThe Prohormone VGF Regulates β Cell Function via Insulin Secretory Granule Biogenesis
Stephens SB, Edwards RJ, Sadahiro M, Lin WJ, Jiang C, Salton SR, Newgard CB. The Prohormone VGF Regulates β Cell Function via Insulin Secretory Granule Biogenesis. Cell Reports 2017, 20: 2480-2489. PMID: 28877479, PMCID: PMC5624795, DOI: 10.1016/j.celrep.2017.08.050.Peer-Reviewed Original Research
2016
Embryonic ablation of neuronal VGF increases energy expenditure and reduces body weight
Jiang C, Lin WJ, Sadahiro M, Shin AC, Buettner C, Salton SR. Embryonic ablation of neuronal VGF increases energy expenditure and reduces body weight. Neuropeptides 2016, 64: 75-83. PMID: 28024880, PMCID: PMC5478485, DOI: 10.1016/j.npep.2016.12.005.Peer-Reviewed Original ResearchConceptsVGF knockout miceKnockout miceBody weightPeripheral endocrineEnergy expenditureAdult miceVGF-derived peptide TLQP-21Peptide TLQP-21Diet-induced obesityEmbryonic CNS neuronsICV deliverySynapsin-CreAAV-CreTLQP-21Arcuate nucleusCNS neuronsVentromedial hypothalamusReduced adiposityFemale miceMale miceEmbryonic ablationAdult neuronsExcitatory neuronsHypermetabolic phenotypeEmbryonic neurons
2015
VGF and Its C-Terminal Peptide TLQP-62 Regulate Memory Formation in Hippocampus via a BDNF-TrkB-Dependent Mechanism
Lin WJ, Jiang C, Sadahiro M, Bozdagi O, Vulchanova L, Alberini CM, Salton SR. VGF and Its C-Terminal Peptide TLQP-62 Regulate Memory Formation in Hippocampus via a BDNF-TrkB-Dependent Mechanism. Journal Of Neuroscience 2015, 35: 10343-10356. PMID: 26180209, PMCID: PMC4502270, DOI: 10.1523/jneurosci.0584-15.2015.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAvoidance LearningBrainBrain-Derived Neurotrophic FactorConditioning, PsychologicalDown-RegulationEnzyme ActivatorsEnzyme InhibitorsExcitatory Postsynaptic PotentialsFlavanonesGreen Fluorescent ProteinsIn Vitro TechniquesMaleMemoryMiceMice, Inbred C57BLMice, TransgenicNerve Growth FactorsNeuronsNeuropeptidesPeptidesRatsRats, Long-EvansReceptor, trkBConceptsVGF-derived peptide TLQP-62BDNF-TrkB signalingTrkB receptor signalingTLQP-62BDNF-TrkBHippocampal memory consolidationMemory formationVGF expressionActivity-dependent BDNF secretionMemory consolidationReceptor signalingLong-term memory formationSecretion of BDNFBDNF/TrkBAlternative treatment modalitySynaptic plasticity markersHippocampal slice preparationAdult mouse hippocampusExpression of VGFImpaired fear memoryImpairs memory formationSubsequent CREB phosphorylationBDNF secretionFear memory formationTrkB receptorsErrata
Fargali S, Garcia AL, Sadahiro M, Jiang C, Janssen WG, Lin WJ, Cogliani V, Elste A, Mortillo S, Cero C, Veitenheimer B, Graiani G, Pasinetti GM, Mahata SK, Osborn JW, Huntley GW, Phillips GR, Benson DL, Bartolomucci A, Salton SR. Errata. The FASEB Journal 2015, 29: 2679-2679. PMID: 26032479, PMCID: PMC4763872, DOI: 10.1096/fj.13-239509err.Peer-Reviewed Original ResearchRole of VGF-Derived Carboxy-Terminal Peptides in Energy Balance and Reproduction: Analysis of “Humanized” Knockin Mice Expressing Full-Length or Truncated VGF
Sadahiro M, Erickson C, Lin WJ, Shin AC, Razzoli M, Jiang C, Fargali S, Gurney A, Kelley KA, Buettner C, Bartolomucci A, Salton SR. Role of VGF-Derived Carboxy-Terminal Peptides in Energy Balance and Reproduction: Analysis of “Humanized” Knockin Mice Expressing Full-Length or Truncated VGF. Endocrinology 2015, 156: 1724-1738. PMID: 25675362, PMCID: PMC4398760, DOI: 10.1210/en.2014-1826.Peer-Reviewed Original ResearchConceptsEnergy expenditureRole of VGFWild-type miceKnockin mouse modelGlucose toleranceFemale miceGlucose homeostasisMouse modelBody weightReproductive functionKnockin miceVGF peptidesMiceVGF proteinMetabolic phenotypeInfertile miceSingle nucleotide polymorphismsFat storageTerminal peptidesTargeted deletionCarboxy-terminal peptideVGFObesityCritical regulatorC-terminal region
2014
The granin VGF promotes genesis of secretory vesicles, and regulates circulating catecholamine levels and blood pressure
Fargali S, Garcia AL, Sadahiro M, Jiang C, Janssen WG, Lin W, Cogliani V, Elste A, Mortillo S, Cero C, Veitenheimer B, Graiani G, Pasinetti GM, Mahata SK, Osborn JW, Huntley GW, Phillips GR, Benson DL, Bartolomucci A, Salton SR. The granin VGF promotes genesis of secretory vesicles, and regulates circulating catecholamine levels and blood pressure. The FASEB Journal 2014, 28: 2120-2133. PMID: 24497580, PMCID: PMC3986843, DOI: 10.1096/fj.13-239509.Peer-Reviewed Original ResearchConceptsBlood pressureCatecholamine levelsLarge dense-core vesiclesTLQP-21Peptide TLQP-21VGF knockout miceSystolic blood pressureNoradrenergic chromaffin cellsMouse adrenal medullaDense-core vesiclesChronic administrationPlasma epinephrineNeurochemical changesAdrenal norepinephrineEpinephrine contentAdrenal medullaChromaffin cellsCore vesiclesGranin proteinsVGFSignificant increaseMiceSecretionSecretion of proteinsHypertension