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 accumbens
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 receptors