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 plaques
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 accumbensRole 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 expression
2015
Role 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