Alpha-SNAP (M105I) mutation promotes neuronal differentiation of neural stem/progenitor cells through overactivation of AMPK

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datacite.alternateIdentifier.citationFrontiers in Cell and Developmental Biology, 11, 2023
datacite.alternateIdentifier.doi10.3389/fcell.2023.1061777
datacite.alternateIdentifier.issn2296-634X
datacite.creatorBustamante-Barrientos, Felipe A.
datacite.creatorMéndez-Ruette, Maxs
datacite.creatorMolina, Luis
datacite.creatorKoning, Tania
datacite.creatorEhrenfeld, Pamela
datacite.creatorGonzález, Carlos Barcia
datacite.creatorWyneken, Ursula
datacite.creatorHenzi, Roberto
datacite.creatorBátiz, Luis Federico
datacite.date2023
datacite.rightsAcceso abierto
datacite.subjectAmpk Phosphatase
datacite.subjectBrain Development
datacite.subjectCell Fate
datacite.subjectCell Metabolism
datacite.subjectHydrocephalus With Hop Gait
datacite.subjectNeurogenesis
datacite.subjectProliferation
datacite.subjectVentricular Zone
datacite.subject5 Amino 4 Imidazolecarboxamide Riboside
datacite.subjectHydroxymethylglutaryl Coenzyme A Reductase Kinase
datacite.subjectAicar
datacite.subject5 Amino 4 Imidazolecarboxamide Riboside
datacite.subjectAlpha Soluble N Ethylmaleimide Sensitive Factor Attachment Protein
datacite.subjectCompound C
datacite.subjectHydroxymethylglutaryl Coenzyme A Reductase Kinase
datacite.subjectProtein Serine Threonine Kinase Inhibitor
datacite.subjectSoluble N Ethylmaleimide Sensitive Factor Attachment Protein
datacite.subjectUnclassified Drug
datacite.subjectAmpk Signaling
datacite.subjectAnimal Cell
datacite.subjectAnimal Experiment
datacite.subjectAnimal Model
datacite.subjectAnimal Tissue
datacite.subjectArticle
datacite.subjectBrain Development
datacite.subjectBrain Region
datacite.subjectBrain Ventricle
datacite.subjectBrdu Assay
datacite.subjectCell Fate
datacite.subjectCell Proliferation
datacite.subjectControlled Study
datacite.subjectDevelopmental Stage
datacite.subjectEmbryo
datacite.subjectEnzyme Activation
datacite.subjectEnzyme Activity
datacite.subjectEnzyme Phosphorylation
datacite.subjectFemale
datacite.subjectGait Disorder
datacite.subjectGene Mutation
datacite.subjectHydrocephalus
datacite.subjectHydrocephalus With Hop Gait
datacite.subjectImmunofluorescence
datacite.subjectIn Vitro Study
datacite.subjectMale
datacite.subjectMicroscopy
datacite.subjectMouse
datacite.subjectNerve Cell Differentiation
datacite.subjectNeural Stem Cell
datacite.subjectNewborn
datacite.subjectNonhuman
datacite.subjectPathogenesis
datacite.subjectPhenotype
datacite.subjectProtein Expression
datacite.subjectSubventricular Zone
datacite.subjectWestern Blotting
datacite.titleAlpha-SNAP (M105I) mutation promotes neuronal differentiation of neural stem/progenitor cells through overactivation of AMPK
dc.contributor.authorHENZI MIRANDA, ROBERTO PABLO JAVIER
dc.description.abstractBackground: The M105I point mutation in ?-SNAP (Soluble N-ethylmaleimide-sensitive factor attachment protein-alpha) leads in mice to a complex phenotype known as hyh (hydrocephalus with hop gait), characterized by cortical malformation and hydrocephalus, among other neuropathological features. Studies performed by our laboratory and others support that the hyh phenotype is triggered by a primary alteration in embryonic neural stem/progenitor cells (NSPCs) that leads to a disruption of the ventricular and subventricular zones (VZ/SVZ) during the neurogenic period. Besides the canonical role of ?-SNAP in SNARE-mediated intracellular membrane fusion dynamics, it also negatively modulates AMP-activated protein kinase (AMPK) activity. AMPK is a conserved metabolic sensor associated with the proliferation/differentiation balance in NSPCs. Methods: Brain samples from hyh mutant mice (hydrocephalus with hop gait) (B6C3Fe-a/a-Napahyh/J) were analyzed by light microscopy, immunofluorescence, and Western blot at different developmental stages. In addition, NSPCs derived from WT and hyh mutant mice were cultured as neurospheres for in vitro characterization and pharmacological assays. BrdU labeling was used to assess proliferative activity in situ and in vitro. Pharmacological modulation of AMPK was performed using Compound C (AMPK inhibitor) and AICAR (AMPK activator). Results: ?-SNAP was preferentially expressed in the brain, showing variations in the levels of ?-SNAP protein in different brain regions and developmental stages. NSPCs from hyh mice (hyh-NSPCs) displayed reduced levels of ?-SNAP and increased levels of phosphorylated AMPK? (pAMPK?Thr172), which were associated with a reduction in their proliferative activity and a preferential commitment with the neuronal lineage. Interestingly, pharmacological inhibition of AMPK in hyh-NSPCs increased proliferative activity and completely abolished the increased generation of neurons. Conversely, AICAR-mediated activation of AMPK in WT-NSPCs reduced proliferation and boosted neuronal differentiation. Discussion: Our findings support that ?-SNAP regulates AMPK signaling in NSPCs, further modulating their neurogenic capacity. The naturally occurring M105I mutation of ?-SNAP provokes an AMPK overactivation in NSPCs, thus connecting the ?-SNAP/AMPK axis with the etiopathogenesis and neuropathology of the hyh phenotype. © 2023 Elsevier B.V., All rights reserved.
dc.description.ia_keywordampk, snap, nspcs, mice, activity, mutation, protein
dc.formatPDF
dc.identifier.urihttps://repositoriodigital.uct.cl/handle/10925/5279
dc.language.isoen
dc.publisherFrontiers Media
dc.relationinstname: ANID
dc.relationreponame: Repositorio Digital RI2.0
dc.rights.driverinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/
dc.sourceFrontiers in Cell and Developmental Biology
dc.subject.ia_oecd1nCiencias Naturales
dc.subject.ia_oecd2nCiencias Biológicas
dc.subject.ia_oecd3nBiología General
dc.type.driverinfo:eu-repo/semantics/article
dc.type.driverhttp://purl.org/coar/resource_type/c_2df8fbb1
dc.type.openaireinfo:eu-repo/semantics/publishedVersion
dspace.entity.typePublication
oaire.citationEdition2023
oaire.citationTitleFrontiers in Cell and Developmental Biology
oaire.citationVolume11
oaire.fundingReferenceANID FONDECYT 1141015, 1211384, 1200693, 1201635, 1150176 (Regulares), 3190646 (Postdoctorado), 3220204 (Postdoctorado)
oaire.fundingReferenceANID COVID0706
oaire.fundingReferenceANID FONDEF ID19I10116
oaire.fundingReferenceUANDES FAI PhD Scholarship, IMPACT PhD Scholarship
oaire.fundingReferenceCONICYT Doctorado Nacional 21160084
oaire.licenseConditionObra bajo licencia Creative Commons Atribución 4.0 Internacional
oaire.licenseCondition.urihttps://creativecommons.org/licenses/by/4.0/
oaire.resourceTypeArtículo
oaire.resourceType.enArticle
relation.isAuthorOfPublicationebda31a9-8d25-4163-8c7d-028f8f44ef33
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uct.comunidadRecursos Naturalesen_US
uct.departamentoDepartamento de Ciencias Veterinarias y Salud Pública
uct.facultadFacultad de Recursos Naturales
uct.indizacionScience Citation Index Expanded - SCIE
uct.indizacionSCOPUS
uct.indizacionWOS
uct.indizacionDOAJ
uct.indizacionPubMed
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