2024
Antagonism between neuropeptides and monoamines in a distributed circuit for pathogen avoidance
Marquina-Solis J, Feng L, Vandewyer E, Beets I, Hawk J, Colón-Ramos D, Yu J, Fox B, Schroeder F, Bargmann C. Antagonism between neuropeptides and monoamines in a distributed circuit for pathogen avoidance. Cell Reports 2024, 43: 114042. PMID: 38573858, PMCID: PMC11063628, DOI: 10.1016/j.celrep.2024.114042.Peer-Reviewed Original ResearchConceptsFLP-1 neuropeptidesBacterium Pseudomonas aeruginosa PA14Pathogen avoidanceGrowth factor BNematode Caenorhabditis elegansC. elegansCaenorhabditis elegansAvoidance signalPathogen infectionFlp-1NeuropeptidePathogensNeuronsMultiple mechanismsMultiple neuronsInfectionNeuromodulationPromote recoveryFactor BAvoidance behaviorAVKPA14NCS-1 protein regulates TRPA1 channel through the PI3K pathway in breast cancer and neuronal cells
Sánchez J, Alemán A, Henao J, Olaya J, Ehrlich B. NCS-1 protein regulates TRPA1 channel through the PI3K pathway in breast cancer and neuronal cells. Journal Of Physiology And Biochemistry 2024, 80: 451-463. PMID: 38564162, PMCID: PMC11074019, DOI: 10.1007/s13105-024-01016-z.Peer-Reviewed Original ResearchConceptsTransient receptor potential channel ankyrin 1Breast cancerPI3K pathwayNCS-1Chemotherapy-induced peripheral neuropathyCa2+ channelsK pathwayCa2+ influxNCS-1 expressionBreast cancer cellsCa2+ sensorCa2+ homeostasisCa2+ dynamicsNeuronal calcium sensor-1MDA-MB-231Fura-2Open probabilityPain sensationAnkyrin 1Peripheral neuropathyTRPA1 channelsCo-immunoprecipitationChannel functionRegulatory componentsCellular pathways
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 ResearchMeSH KeywordsAnimalsDietEnergy MetabolismHomeostasisMiceNeuropeptidesPeptide FragmentsPeptide HormonesConceptsGenetic engineering approachesUnique metabolic phenotypeMass spectrometry identificationPrecursor geneGel digestionGenetic lossTLQP-21Cleavage siteC-terminal arginineGenesMutant sequencesSelective knockoutEssential roleBiological constraintsMetabolic phenotypeMouse linesEnergy homeostasisComposite phenotypeMutant miceValuable resourceVGF geneUse of experimental medicine approaches for the development of novel psychiatric treatments based on orexin receptor modulation
Beckenstrom A, Coloma P, Dawson G, Finlayson A, Malik A, Post A, Steiner M, Potenza M. Use of experimental medicine approaches for the development of novel psychiatric treatments based on orexin receptor modulation. Neuroscience & Biobehavioral Reviews 2023, 147: 105107. PMID: 36828161, PMCID: PMC10165155, DOI: 10.1016/j.neubiorev.2023.105107.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsExperimental medicine approachPerformance outcome measuresPsychiatric disordersMedicine approachReal-world clinical practiceOrexin neuropeptide systemMarkers of efficacyPatient advocacy groupsOrexin modulationReceptor modulationSymptom evaluationReceptor modulatorsClinical studiesMood disordersPreclinical studiesNeuropeptide systemsPsychiatric treatmentAnimal modelsPathological mechanismsClinical practiceClinical researchClinical useBrain functionTranslational researchPotential target
2022
Daam2 Regulates Myelin Structure and the Oligodendrocyte Actin Cytoskeleton through Rac1 and Gelsolin
Cristobal C, Wang C, Zuo Z, Smith J, Lindeke-Myers A, Bellen H, Lee H. Daam2 Regulates Myelin Structure and the Oligodendrocyte Actin Cytoskeleton through Rac1 and Gelsolin. Journal Of Neuroscience 2022, 42: 1679-1691. PMID: 35101966, PMCID: PMC8896627, DOI: 10.1523/jneurosci.1517-21.2022.Peer-Reviewed Original ResearchConceptsGelsolin levelsOL differentiationMyelin sheathCNS functionMorphogenesis 2Motor coordination deficitsActin cytoskeletonWhite matter diseaseMyelin structureConditional knockout miceWhite matter developmentMyelin compactionMyelin decompactionNeuronal healthCKO miceCoordination deficitsFunctional myelinCompact myelin sheathKnockout miceWhite matterPostnatal developmentProper myelin formationOligodendrocytesMyelin formationOL cultures
2021
From Molecule to Behavior: Hypocretin/orexin Revisited From a Sex-dependent Perspective
Gao XB, Horvath TL. From Molecule to Behavior: Hypocretin/orexin Revisited From a Sex-dependent Perspective. Endocrine Reviews 2021, 43: 743-760. PMID: 34792130, PMCID: PMC9277634, DOI: 10.1210/endrev/bnab042.Peer-Reviewed Original ResearchMolecular topography of an entire nervous system
Taylor SR, Santpere G, Weinreb A, Barrett A, Reilly MB, Xu C, Varol E, Oikonomou P, Glenwinkel L, McWhirter R, Poff A, Basavaraju M, Rafi I, Yemini E, Cook SJ, Abrams A, Vidal B, Cros C, Tavazoie S, Sestan N, Hammarlund M, Hobert O, Miller DM. Molecular topography of an entire nervous system. Cell 2021, 184: 4329-4347.e23. PMID: 34237253, PMCID: PMC8710130, DOI: 10.1016/j.cell.2021.06.023.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCaenorhabditis elegansCaenorhabditis elegans ProteinsFluorescent DyesGene Expression Regulation, DevelopmentalGenes, ReporterLarvaNervous SystemNeuronsNeuropeptidesNucleotide MotifsRegulatory Sequences, Nucleic AcidRNA-SeqSignal TransductionTranscription FactorsTranscription, GeneticConceptsGene expressionSpecific gene familiesCis-regulatory elementsNeuron-specific gene expressionIndividual neuron classesSingle-cell resolutionGene expression profilesNeuron classesGene familyAdhesion proteinsNeuropeptide genesExpression profilesExpression dataEntire nervous systemCombinatorial expressionMolecular topographyNervous systemSynaptic specificityNeuropeptide receptorsExpressionPotential roleWiring diagramComputational approachGenesProteinDisruption of NEUROD2 causes a neurodevelopmental syndrome with autistic features via cell-autonomous defects in forebrain glutamatergic neurons
Runge K, Mathieu R, Bugeon S, Lafi S, Beurrier C, Sahu S, Schaller F, Loubat A, Herault L, Gaillard S, Pallesi-Pocachard E, Montheil A, Bosio A, Rosenfeld JA, Hudson E, Lindstrom K, Mercimek-Andrews S, Jeffries L, van Haeringen A, Vanakker O, Van Hecke A, Amrom D, Küry S, Ratner C, Jethva R, Gamble C, Jacq B, Fasano L, Santpere G, Lorente-Galdos B, Sestan N, Gelot A, Giacuzz S, Goebbels S, Represa A, Cardoso C, Cremer H, de Chevigny A. Disruption of NEUROD2 causes a neurodevelopmental syndrome with autistic features via cell-autonomous defects in forebrain glutamatergic neurons. Molecular Psychiatry 2021, 26: 6125-6148. PMID: 34188164, PMCID: PMC8760061, DOI: 10.1038/s41380-021-01179-x.Peer-Reviewed Original ResearchConceptsLayer 5 neuronsKO miceForebrain glutamatergic neuronsTranscription factor NeuroD2Forebrain excitatory neuronsNeurodevelopmental disordersAutism spectrum disorderCortical projection neuronsPatch-clamp recordingsIntellectual disabilitySocial interaction deficitsSpontaneous seizuresCerebral cortexGlutamatergic neuronsSpine densityProjection neuronsIntrinsic excitabilityNervous system developmentNeuronal excitabilityExcitatory neuronsJuvenile miceBulk RNA sequencingSynaptic functionNeurobehavioral featuresDysregulated expressionConditional RAC1 knockout in motor neurons restores H-reflex rate-dependent depression after spinal cord injury
Benson CA, Olson KL, Patwa S, Reimer ML, Bangalore L, Hill M, Waxman SG, Tan AM. Conditional RAC1 knockout in motor neurons restores H-reflex rate-dependent depression after spinal cord injury. Scientific Reports 2021, 11: 7838. PMID: 33837249, PMCID: PMC8035187, DOI: 10.1038/s41598-021-87476-5.Peer-Reviewed Original ResearchConceptsSpinal cord injuryDendritic spine dysgenesisMotor neuronsSpine dysgenesisSCI animalsHyperexcitability disordersCord injurySpinal alpha motor neuronsVentral horn motor neuronsAbnormal dendritic spine morphologyRac1 knockoutH-reflex pathwayRate-dependent depressionAlpha motor neuronsDevelopment of spasticityAdeno-associated viralMushroom dendritic spinesSpine head sizeOverall spine lengthDendritic spine morphologyRac1 protein expressionNeuronal hyperexcitabilityMajor complicationsClinical symptomsReflex excitabilityComprehensive somatosensory and neurological phenotyping of NCS1 knockout mice
Nguyen LD, Nolte LG, Tan WJT, Giuvelis D, Santos-Sacchi J, Bilsky E, Ehrlich BE. Comprehensive somatosensory and neurological phenotyping of NCS1 knockout mice. Scientific Reports 2021, 11: 2372. PMID: 33504822, PMCID: PMC7840744, DOI: 10.1038/s41598-021-81650-5.Peer-Reviewed Original ResearchConceptsNeuronal calcium sensor-1Peripheral nervous systemNervous systemMale miceKnockout micePaclitaxel-induced peripheral neuropathyKO modelKO male miceNCS1 expressionMammalian nervous systemPrecise physiological significanceSex-specific effectsPeripheral neuropathyFemale miceModulatory roleBehavioral testsPharmacological targetsMiceNeurodegenerative diseasesClinical interestMemory acquisitionMotor performancePathological statesAffective behaviorDiseaseExpansion of NEUROD2 phenotypes to include developmental delay without seizures
Mis EK, Sega AG, Signer RH, Cartwright T, Ji W, Martinez‐Agosto J, Nelson SF, Palmer CGS, Lee H, Mitzelfelt T, Konstantino M, Network U, Jeffries L, Khokha MK, Marco E, Martin MG, Lakhani SA. Expansion of NEUROD2 phenotypes to include developmental delay without seizures. American Journal Of Medical Genetics Part A 2021, 185: 1076-1080. PMID: 33438828, PMCID: PMC8212414, DOI: 10.1002/ajmg.a.62064.Peer-Reviewed Original ResearchConceptsDevelopmental delayEarly-onset seizuresDe novo heterozygous variantsNovo heterozygous variantsDifferentiation factor 2Xenopus laevis tadpolesHeterozygous variantsSeizuresNeuronal differentiationParental studiesFunctional testingMissense variantsPatient variantsFunctional evidenceFactor 2Vivo assaysLaevis tadpolesVariant pathogenicityFunction effectsAdolescentsVariants
2020
Stac protein regulates release of neuropeptides
Hsu IU, Linsley JW, Zhang X, Varineau JE, Berkhoudt DA, Reid LE, Lum MC, Orzel AM, Leflein A, Xu H, Collins CA, Hume RI, Levitan ES, Kuwada JY. Stac protein regulates release of neuropeptides. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 29914-29924. PMID: 33168737, PMCID: PMC7703553, DOI: 10.1073/pnas.2009224117.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, Genetically ModifiedBehavior Observation TechniquesBehavior, AnimalCalcium ChannelsDrosophila melanogasterDrosophila ProteinsFemaleIntracellular Signaling Peptides and ProteinsIntravital MicroscopyLarvaMaleModels, AnimalMotor NeuronsMuscle, SkeletalNeuromuscular JunctionNeuropeptidesOptical ImagingPatch-Clamp TechniquesPresynaptic TerminalsConceptsSTAC proteinsRelease of neuropeptidesVertebrate skeletal muscleSubset of neuronsMolecular regulationGenetic manipulationKey regulatorMotor neuronsCytosolic CaNumerous neural functionsSmall familyCentral nervous systemExcitation-contraction couplingGenesSkeletal muscleL-type CaProteinNeuropeptide releaseNervous systemNeural functionDrosophilaNeuropeptidesVertebratesNeuronsRegulatorTopologically Guided Prioritization of Candidate Gene Transcripts Coexpressed with the 5-HT1A Receptor by Combining In Vivo PET and Allen Human Brain Atlas Data
Unterholzner J, Gryglewski G, Philippe C, Seiger R, Pichler V, Godbersen GM, Berroterán-Infante N, Murgaš M, Hahn A, Wadsak W, Mitterhauser M, Kasper S, Lanzenberger R. Topologically Guided Prioritization of Candidate Gene Transcripts Coexpressed with the 5-HT1A Receptor by Combining In Vivo PET and Allen Human Brain Atlas Data. Cerebral Cortex 2020, 30: 3771-3780. PMID: 31989157, PMCID: PMC7232988, DOI: 10.1093/cercor/bhz341.Peer-Reviewed Original ResearchConceptsMRNA expressionRole of BDNFSerotonin 1A receptorEfficacy of drugsTreatment of disordersReceptor subtypesHealthy subjectsPsychiatric drugsBrain tissueCortical regionsVivo PETSerotonergic functioningViable targetDrugsSpearman's rhoCandidate gene transcriptsReceptorsCoexpression patternsRelative inaccessibility
2019
Weak membrane interactions allow Rheb to activate mTORC1 signaling without major lysosome enrichment
Angarola B, Ferguson SM. Weak membrane interactions allow Rheb to activate mTORC1 signaling without major lysosome enrichment. Molecular Biology Of The Cell 2019, 30: 2750-2760. PMID: 31532697, PMCID: PMC6789162, DOI: 10.1091/mbc.e19-03-0146.Peer-Reviewed Original ResearchMeSH KeywordsAmino AcidsAnimalsChlorocebus aethiopsCOS CellsEndoplasmic ReticulumHeLa CellsHumansLysosomesMechanistic Target of Rapamycin Complex 1Monomeric GTP-Binding ProteinsMultiprotein ComplexesNeuropeptidesPrenylationRas Homolog Enriched in Brain ProteinSignal TransductionTOR Serine-Threonine KinasesConceptsMembrane interactionsC-terminal CAAX motifTransient membrane interactionsEndoplasmic reticulum localizationMTOR complex 1CAAX motifRheb GTPaseER membraneMTORC1 activationSubcellular localizationTargeting motifRhebLysosome enrichmentHuman cellsFunctional assaysTargeting mechanismStable interactionStable localizationLysosomesFurther systematic analysisMotifActivationInhibition of Endocytosis of Clathrin-Mediated Angiotensin II Receptor Type 1 in Podocytes Augments Glomerular Injury
Inoue K, Tian X, Velazquez H, Soda K, Wang Z, Pedigo CE, Wang Y, Cross E, Groener M, Shin JW, Li W, Hassan H, Yamamoto K, Mundel P, Ishibe S. Inhibition of Endocytosis of Clathrin-Mediated Angiotensin II Receptor Type 1 in Podocytes Augments Glomerular Injury. Journal Of The American Society Of Nephrology 2019, 30: 2307-2320. PMID: 31511362, PMCID: PMC6900791, DOI: 10.1681/asn.2019010053.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAlbuminuriaAngiotensin IIAnimalsCalcium SignalingCells, CulturedClathrin-Coated VesiclesCreatinineDynamin IDynamin IIEndocytosisGlomerulonephritisHemodynamicsKidney GlomerulusMaleMiceMice, KnockoutNeuropeptidesPodocytesPseudopodiarac1 GTP-Binding ProteinReceptor, Angiotensin, Type 1ConceptsDouble knockout miceAngiotensin II receptor type 1Receptor type 1Renin-angiotensin system blockersType 1Renin-angiotensin systemPrimary podocytesEffects of AngIIImproved albuminuriaSystem blockersGlomerular hyperfiltrationGlomerular filtration barrierGlomerular injuryKidney functionAngiotensin IIKidney failurePodocyte injuryProtective effectCalcium influxRac1 activationAngII stimulationMice exhibitAngIIGenetic ablationMiceInsight Into the Emerging Role of Striatal Neurotransmitters in the Pathophysiology of Parkinson’s Disease and Huntington’s Disease: A Review
Jamwal S, Kumar P. Insight Into the Emerging Role of Striatal Neurotransmitters in the Pathophysiology of Parkinson’s Disease and Huntington’s Disease: A Review. Current Neuropharmacology 2019, 17: 165-175. PMID: 29512464, PMCID: PMC6343208, DOI: 10.2174/1570159x16666180302115032.Peer-Reviewed Original ResearchConceptsParkinson's diseaseHuntington's diseaseStriatal neurotransmittersNeuronal deathNeurotransmitter levelsAltered neurotransmitters levelBasal ganglia regionsExcitotoxic neuronal deathNeurotransmitter alterationsBrain dopaminePathophysiological basisBasal gangliaGanglia regionsMovement disordersPreclinical studiesReceptor densitySpecific drugsCoordinated body movementsDiseaseNeurotransmittersAltered levelsOxidative stressExact mechanismMitochondrial dysfunctionImportant neurotransmitterSerotonin and neuropeptides are both released by the HSN command neuron to initiate C. elegans egg laying
Brewer JC, Olson AC, Collins KM, Koelle MR. Serotonin and neuropeptides are both released by the HSN command neuron to initiate C. elegans egg laying. PLOS Genetics 2019, 15: e1007896. PMID: 30677018, PMCID: PMC6363226, DOI: 10.1371/journal.pgen.1007896.Peer-Reviewed Original ResearchConceptsHermaphrodite-specific neuronsEgg-laying defectsNLP-3C. elegansEgg-laying musclesEgg-laying circuitDirect postsynaptic targetsEgg-laying behaviorSerotonergic Hermaphrodite Specific NeuronsMuscle cellsSmall molecule neurotransmittersNull mutantsHSN neuronsDouble mutantSingle mutantsMutant animalsSerotonergic neuronsWild-type animalsSevere defectsMutantsElegansNeuropeptide substance PMammalian brainEggsSpecific neurons
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 accumbensAre Neuropeptide-Reactive T Cells behind Narcolepsy?
Deerhake ME, Barclay WE, Shinohara ML. Are Neuropeptide-Reactive T Cells behind Narcolepsy? Immunity 2018, 49: 796-798. PMID: 30462995, DOI: 10.1016/j.immuni.2018.11.002.Peer-Reviewed Original ResearchDe novo pathogenic variants in neuronal differentiation factor 2 (NEUROD2) cause a form of early infantile epileptic encephalopathy
Sega AG, Mis EK, Lindstrom K, Mercimek-Andrews S, Ji W, Cho MT, Juusola J, Konstantino M, Jeffries L, Khokha MK, Lakhani SA. De novo pathogenic variants in neuronal differentiation factor 2 (NEUROD2) cause a form of early infantile epileptic encephalopathy. Journal Of Medical Genetics 2018, 56: 113. PMID: 30323019, DOI: 10.1136/jmedgenet-2018-105322.Peer-Reviewed Original ResearchConceptsEarly infantile epileptic encephalopathyInfantile epileptic encephalopathyEpileptic encephalopathyPatient variantsDe novo pathogenic variantsNovel de novo variantNovo pathogenic variantsEarly-onset refractory seizuresDifferentiation factor 2Whole-exome sequencingNeuronal differentiation factorRefractory seizuresSignificant developmental delaySpontaneous seizuresUnderlying etiologyEctopic neuronsDe novo variantsPatient's conditionEncephalopathyPathogenic variantsSevere disordersDevelopmental delayUnrelated childrenExome sequencingGene mutations
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