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dc.creatorSuárez Pereira, Irenees
dc.creatorGarcía Domínguez, Irenees
dc.creatorBravo, L.es
dc.creatorSantiago Pavón, Martinianoes
dc.creatorGarcía Revilla, Juanes
dc.creatorEspinosa Oliva, Ana Maríaes
dc.creatorAlonso Bellido, Isabel Maríaes
dc.creatorLópez Martín, Césares
dc.creatorPérez Villegas, Eva Maríaes
dc.creatorArmengol, J. A.es
dc.creatorBerrocoso, E.es
dc.creatorVenero Recio, José Luises
dc.creatorMartínez de Pablos, Rocíoes
dc.creatorRuiz Laza, Rocíoes
dc.date.accessioned2022-05-16T18:03:52Z
dc.date.available2022-05-16T18:03:52Z
dc.date.issued2022
dc.identifier.citationSuárez Pereira, I., García Domínguez, I., Bravo, L., Santiago Pavón, M., García Revilla, J., Espinosa Oliva, A.M.,...,Ruiz Laza, R. (2022). The Absence of Caspase-8 in the Dopaminergic System Leads to Mild Autism-like Behavior. Frontiers in Cell and Developmental Biology, 10, 839715.
dc.identifier.issn2296-634Xes
dc.identifier.urihttps://hdl.handle.net/11441/133356
dc.description.abstractIn the last decade, new non-apoptotic roles have been ascribed to apoptotic caspases. This family of proteins plays an important role in the sculpting of the brain in the early stages of development by eliminating excessive and nonfunctional synapses and extra cells. Consequently, impairments in this process can underlie many neurological and mental illnesses. This view is particularly relevant to dopamine because it plays a pleiotropic role in motor control, motivation, and reward processing. In this study, we analyze the effects of the elimination of caspase-8 (CASP8) on the development of catecholaminergic neurons using neurochemical, ultrastructural, and behavioral tests. To do this, we selectively delete the CASP8 gene in cells that express tyrosine hydroxylase with the help of recombination through the Cre-loxP system. Our results show that the number of dopaminergic neurons increases in the substantia nigra. In the striatum, the basal extracellular level of dopamine and potassium-evoked dopamine release decreased significantly in mice lacking CASP8, clearly showing the low dopamine functioning in tissues innervated by this neurotransmitter. This view is supported by electron microscopy analysis of striatal synapses. Interestingly, behavioral analysis demonstrates that mice lacking CASP8 show changes reminiscent of autism spectrum disorders (ASD). Our research reactivates the possible role of dopamine transmission in the pathogenesis of ASD and provides a mild model of autism.es
dc.description.sponsorshipMinisterio de Economía y Competitividad RTI2018-098645-B-I00, PID2019-109569GB-I00, RTI2018-099778-B-I00es
dc.description.sponsorshipJunta de Andalucía P18-RT-1372, US-1264806, PI-0080-2017, PI-0009-2017, PI-0134-2018, PEMP-0008-2020, P20_00958, CTS-510es
dc.description.sponsorshipInstituto de Salud Carlos III PI18/01691es
dc.description.sponsorshipInstituto de Investigación e Innovación en Ciencias Biomédicas de Cádiz-INiBICA LI19/06IN-CO22, IN-C09es
dc.description.sponsorshipEuropean Union 955684es
dc.formatapplication/pdfes
dc.format.extent17 p.es
dc.language.isoenges
dc.publisherFrontiers Media S.A.es
dc.relation.ispartofFrontiers in Cell and Developmental Biology, 10, 839715.
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectAutism spectrum disorderes
dc.subjectBehavioral testes
dc.subjectCaspase 8es
dc.subjectDopaminergic systemes
dc.subjectElectron microscopyes
dc.subjectSynapsises
dc.titleThe Absence of Caspase-8 in the Dopaminergic System Leads to Mild Autism-like Behaviores
dc.typeinfo:eu-repo/semantics/articlees
dcterms.identifierhttps://ror.org/03yxnpp24
dc.type.versioninfo:eu-repo/semantics/publishedVersiones
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses
dc.contributor.affiliationUniversidad de Sevilla. Departamento de Bioquímica y Biología Moleculares
dc.relation.projectIDRTI2018-098645-B-I00es
dc.relation.projectIDPID2019-109569GB-I00es
dc.relation.projectIDRTI2018-099778-B-I00es
dc.relation.projectIDP18-RT-1372es
dc.relation.projectIDUS-1264806es
dc.relation.projectIDPI-0080-2017es
dc.relation.projectIDPI-0009-2017es
dc.relation.projectIDPI-0134-2018es
dc.relation.projectIDPEMP-0008-2020es
dc.relation.projectIDP20_00958es
dc.relation.projectIDCTS-510es
dc.relation.projectIDPI18/01691es
dc.relation.projectIDLI19/06IN-CO22es
dc.relation.projectIDIN-C09es
dc.relation.projectID955684es
dc.relation.publisherversionhttps://doi.org/10.3389/fcell.2022.839715es
dc.identifier.doi10.3389/fcell.2022.839715es
dc.journaltitleFrontiers in Cell and Developmental Biologyes
dc.publication.volumen10es
dc.publication.initialPage839715es
dc.contributor.funderMinisterio de Economía y Competitividad (MINECO). Españaes
dc.contributor.funderJunta de Andalucíaes
dc.contributor.funderInstituto de Salud Carlos IIIes
dc.contributor.funderEuropean Union (UE)es

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