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
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 accumbens
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
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 ResearchMeSH KeywordsAnimalsBody WeightDietEnergy MetabolismHypothalamusMiceNerve Growth FactorsNeuronsNeuropeptidesObesityConceptsVGF 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 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
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
2012
Role of Neurotrophins in the Development and Function of Neural Circuits That Regulate Energy Homeostasis
Fargali S, Sadahiro M, Jiang C, Frick AL, Indall T, Cogliani V, Welagen J, Lin WJ, Salton SR. Role of Neurotrophins in the Development and Function of Neural Circuits That Regulate Energy Homeostasis. Journal Of Molecular Neuroscience 2012, 48: 654-659. PMID: 22581449, PMCID: PMC3480664, DOI: 10.1007/s12031-012-9790-9.Peer-Reviewed Original ResearchMeSH KeywordsAdipose TissueAnimalsAutonomic Fibers, PostganglionicBasal MetabolismBrain StemCorticotropin-Releasing HormoneEatingEnergy MetabolismGene Expression RegulationGlucocorticoidsHomeostasisHumansHypothalamusNerve Growth FactorsNeural PathwaysNeuropeptidesReceptors, Nerve Growth FactorSignal TransductionSpinal CordSympathetic Nervous SystemConceptsNeurotrophic growth factorsNeurotrophic factorGrowth factorBrain-derived neurotrophic factorEnergy homeostasisRole of neurotrophinsSympathetic nervous systemPeripheral metabolic tissuesWhite adipose tissueNerve growth factorCiliary neurotrophic factorCentral nervous system developmentNeurotrophin-4/5Neurotrophin-3Neurotrophin familyNeuronal survivalNervous system developmentSpinal cordAdipose tissueNervous systemCircuit formationNeural circuitsMetabolic tissuesEnergy expenditureCritical gene products