2023
Neuronal transcriptome, tau and synapse loss in Alzheimer’s knock-in mice require prion protein
Stoner A, Fu L, Nicholson L, Zheng C, Toyonaga T, Spurrier J, Laird W, Cai Z, Strittmatter S. Neuronal transcriptome, tau and synapse loss in Alzheimer’s knock-in mice require prion protein. Alzheimer's Research & Therapy 2023, 15: 201. PMID: 37968719, PMCID: PMC10647125, DOI: 10.1186/s13195-023-01345-z.Peer-Reviewed Original ResearchConceptsSynapse lossDKI miceTau accumulationBrain immune activationNeural network dysfunctionPhospho-tau accumulationAccumulation of tauNeuronal genesInflammatory markersAD miceAβ levelsPrion proteinDystrophic neuritesImmune activationTau pathologyNeuronal gene expressionAmyloid-β OligomersGliotic reactionNetwork dysfunctionBehavioral deficitsSynaptic failureAD modelMemory impairmentAlzheimer's diseaseFunction of age
2022
Reversal of synapse loss in Alzheimer mouse models by targeting mGluR5 to prevent synaptic tagging by C1Q
Spurrier J, Nicholson L, Fang XT, Stoner AJ, Toyonaga T, Holden D, Siegert TR, Laird W, Allnutt MA, Chiasseu M, Brody AH, Takahashi H, Nies SH, Pérez-Cañamás A, Sadasivam P, Lee S, Li S, Zhang L, Huang YH, Carson RE, Cai Z, Strittmatter SM. Reversal of synapse loss in Alzheimer mouse models by targeting mGluR5 to prevent synaptic tagging by C1Q. Science Translational Medicine 2022, 14: eabi8593. PMID: 35648810, PMCID: PMC9554345, DOI: 10.1126/scitranslmed.abi8593.Peer-Reviewed Original ResearchConceptsPositron emission tomographySilent allosteric modulatorsAlzheimer's diseaseMouse modelPhospho-tau accumulationAged mouse modelAlzheimer mouse modelImmune-mediated attackSAM treatmentMicroglial mediatorsSynaptic engulfmentSynaptic lossAD miceComplement component C1qSynapse lossGlutamate responseSynaptic densityDrug washoutSynaptic localizationTherapeutic benefitCognitive impairmentAllosteric modulatorsEmission tomographyNonhuman primatesComponent C1q
2019
VEGF/VEGFR2 signaling regulates hippocampal axon branching during development
Luck R, Urban S, Karakatsani A, Harde E, Sambandan S, Nicholson L, Haverkamp S, Mann R, Martin-Villalba A, Schuman EM, Acker-Palmer A, de Almodóvar C. VEGF/VEGFR2 signaling regulates hippocampal axon branching during development. ELife 2019, 8: e49818. PMID: 31868583, PMCID: PMC6927742, DOI: 10.7554/elife.49818.Peer-Reviewed Original ResearchConceptsVEGF/VEGFR2Hippocampal axonsAxon branchingVEGF/VEGFR2 signalingHippocampal neurons resultsMouse hippocampal neuronsCA1 neuronsFunctional synapsesCA3 regionHippocampal neuronsNeurons resultsAngiogenic factorsHippocampus developmentAxonsReceptor VEGFR2NeuronsVEGFR2Neuronal networksVEGFNumber of filopodiaVEGFR2 signalingEphrinB2 regulates VEGFR2 during dendritogenesis and hippocampal circuitry development
Harde E, Nicholson L, Cuadrado B, Bissen D, Wigge S, Urban S, Segarra M, de Almodóvar C, Acker-Palmer A. EphrinB2 regulates VEGFR2 during dendritogenesis and hippocampal circuitry development. ELife 2019, 8: e49819. PMID: 31868584, PMCID: PMC6927743, DOI: 10.7554/elife.49819.Peer-Reviewed Original ResearchConceptsVascular endothelial growth factorLong-term potentiationDendritic arborizationCircuitry developmentSpine morphogenesisSpine head sizeEndothelial growth factorVEGFR2 internalizationCA3 synapsesCA3 regionDendritic arborsSpine maturationCompound miceHippocampal neuronsDendritic branchingNervous systemAngiogenic factorsEndothelial cellsGrowth factorNeuronsVEGFR2ArborizationMiceFunctional crosstalkEphrinB2
2017
Regulated viral BDNF delivery in combination with Schwann cells promotes axonal regeneration through capillary alginate hydrogels after spinal cord injury
Liu S, Sandner B, Schackel T, Nicholson L, Chtarto A, Tenenbaum L, Puttagunta R, Müller R, Weidner N, Blesch A. Regulated viral BDNF delivery in combination with Schwann cells promotes axonal regeneration through capillary alginate hydrogels after spinal cord injury. Acta Biomaterialia 2017, 60: 167-180. PMID: 28735026, DOI: 10.1016/j.actbio.2017.07.024.Peer-Reviewed Original ResearchConceptsBrain-derived neurotrophic factorHost spinal cordSpinal cord injurySpinal cordLesion siteSchwann cellsBDNF expressionCord injuryNeurotrophic factorAxonal regenerationBDNF deliveryExpression of BDNFGraft/host interfaceSpinal cord lesion siteAdult mammalian central nervous systemHost/graft interfaceSpinal cord transectionMammalian central nervous systemRat spinal cordCentral nervous systemCaudal spinal cordCaudal injectionHemisection lesionCord transectionCell transplantation
2013
Bone morphogenetic proteins prevent bone marrow stromal cell-mediated oligodendroglial differentiation of transplanted adult neural progenitor cells in the injured spinal cord
Sandner B, Rivera FJ, Caioni M, Nicholson L, Eckstein V, Bogdahn U, Aigner L, Blesch A, Weidner N. Bone morphogenetic proteins prevent bone marrow stromal cell-mediated oligodendroglial differentiation of transplanted adult neural progenitor cells in the injured spinal cord. Stem Cell Research 2013, 11: 758-771. PMID: 23770801, DOI: 10.1016/j.scr.2013.05.003.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Marrow TransplantationBone Morphogenetic Protein 2Bone Morphogenetic Protein 4Cell DifferentiationFemaleHumansImmunohistochemistryMesenchymal Stem Cell TransplantationMesenchymal Stem CellsNeural Stem CellsOligodendrogliaRatsRats, Inbred F344Rats, Sprague-DawleyRats, TransgenicSpinal Cord InjuriesConceptsGrafted neural progenitor cellsNeural progenitor cellsBone marrow stromal cellsAdult neural progenitor cellsOligodendroglial differentiationSpinal cordEffect of BMSCsAdult Fischer 344 ratsLoss of oligodendrogliaProgenitor cellsSpinal cord injuryFischer 344 ratsAdult bone marrowOligodendrogenic effectFunctional recoveryCord injuryLesion cavityInjury siteMarrow stromal cellsBone marrowStromal cellsOligodendrogliaBone morphogenetic protein 2/4Rapid upregulationVivo experiments
2012
Dependence of Regenerated Sensory Axons on Continuous Neurotrophin-3 Delivery
Hou S, Nicholson L, van Niekerk E, Motsch M, Blesch A. Dependence of Regenerated Sensory Axons on Continuous Neurotrophin-3 Delivery. Journal Of Neuroscience 2012, 32: 13206-13220. PMID: 22993437, PMCID: PMC3513675, DOI: 10.1523/jneurosci.5041-11.2012.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceAnimalsAntigensAxonsCell TransplantationCells, CulturedCholera ToxinDisease Models, AnimalDoxycyclineEnzyme-Linked Immunosorbent AssayFemaleGene Expression RegulationGenetic TherapyGlial Fibrillary Acidic ProteinGreen Fluorescent ProteinsHEK293 CellsHumansLamininLeukocyte L1 Antigen ComplexMembrane GlycoproteinsMicrotubule-Associated ProteinsMyelin-Oligodendrocyte GlycoproteinNerve Growth FactorsNerve RegenerationNerve Tissue ProteinsNeurofilament ProteinsNeurotrophin 3ProteoglycansRatsRats, Inbred F344S100 Calcium Binding Protein beta SubunitS100 ProteinsSchwann CellsSciatic NerveSensory Receptor CellsSpinal Cord InjuriesStem Cell TransplantationTime FactorsTransfectionConceptsNT-3 expressionRegenerated sensory axonsRegenerated axonsSensory axonsLesion siteNeurotrophin-3Dorsal column sensory axonsLesion/graft siteNT-3 gene expressionSpinal cord lesion siteCholera toxin βNT-3 deliveryIntrinsic growth capacityBone marrow stromal cellsAxodendritic synapsesConditioning lesionPresynaptic markersAxon numberSpinal cordMarrow stromal cellsSchwann cellsSensory neuronsAdult ratsDoxycycline administrationGraft site