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 MapsProteomics
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 resilience
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 expression
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 receptorsRole 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