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Prenatal treatment with rapamycin restores enhanced hippocampal mGluR-LTD and mushroom spine size in a Down's syndrome mouse model

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dc.contributor.authorUrbano-Gámez, Jesús David
dc.contributor.authorCasañas, Juan José
dc.contributor.authorBenito, Itziar
dc.contributor.authorMontesinos, María Luz
dc.contributor.authoraffiliation[Urbano-Gámez,JD; Casañas,JJ; Benito,I; Montesinos,ML] Departamento de Fisiología Médica Y Biofísica, Universidad de Sevilla, Sevilla, Spain. [Urbano-Gámez,JD; Casañas,JJ; Benito,I; Montesinos,ML] Instituto de Biomedicina de Sevilla, IBIS/Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain. [Benito,I] Servicio de Animalario, Hospital Universitario Virgen Macarena (HUVM), Sevilla, Spain
dc.contributor.funderThis work was funded by the Junta de Andalucía (Spain, Grant P12-CTS-1818), the Ministerio de Economía, Industria y Competitividad (Spain, Grant: SAF2015-65032-R), the Fondo Europeo de Desarrollo Regional (FEDER) and the Fondation Jérôme Lejeune (France).
dc.date.accessioned2022-11-25T09:15:45Z
dc.date.available2022-11-25T09:15:45Z
dc.date.issued2021-05-25
dc.description.abstractDown syndrome (DS) is the most frequent genetic cause of intellectual disability including hippocampal-dependent memory deficits. We have previously reported hippocampal mTOR (mammalian target of rapamycin) hyperactivation, and related plasticity as well as memory deficits in Ts1Cje mice, a DS experimental model. Here we characterize the proteome of hippocampal synaptoneurosomes (SNs) from these mice, and found a predicted alteration of synaptic plasticity pathways, including long term depression (LTD). Accordingly, mGluR-LTD (metabotropic Glutamate Receptor-LTD) is enhanced in the hippocampus of Ts1Cje mice and this is correlated with an increased proportion of a particular category of mushroom spines in hippocampal pyramidal neurons. Remarkably, prenatal treatment of these mice with rapamycin has a positive pharmacological effect on both phenotypes, supporting the therapeutic potential of rapamycin/rapalogs for DS intellectual disability.es_ES
dc.description.versionYeses_ES
dc.identifier.citationUrbano-Gámez JD, Casañas JJ, Benito I, Montesinos ML. Prenatal treatment with rapamycin restores enhanced hippocampal mGluR-LTD and mushroom spine size in a Down's syndrome mouse model. Mol Brain. 2021 May 25;14(1):84es_ES
dc.identifier.doi10.1186/s13041-021-00795-6es_ES
dc.identifier.essn1756-6606
dc.identifier.pmcPMC8152312
dc.identifier.pmid34034796es_ES
dc.identifier.urihttp://hdl.handle.net/10668/4404
dc.journal.titleMolecular Brain
dc.language.isoen
dc.page.number16 p.
dc.publisherBioMed Central, Springer Naturees_ES
dc.relation.publisherversionhttps://molecularbrain.biomedcentral.com/articles/10.1186/s13041-021-00795-6es_ES
dc.rightsAtribución 4.0 Internacional*
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectmGluR-LTDes_ES
dc.subjectmTORes_ES
dc.subjectDendritic spineses_ES
dc.subjectProteomicses_ES
dc.subjectDown syndromees_ES
dc.subjectSynaptoneurosomeses_ES
dc.subjectTrisomy 21es_ES
dc.subjectLong term depressiones_ES
dc.subjectIntellectual disabilityes_ES
dc.subjectHippocampuses_ES
dc.subjectNeuronal synapsees_ES
dc.subjectReceptores de glutamato metabotrópicoes_ES
dc.subjectInhibidores mTORes_ES
dc.subjectEspinas dendríticases_ES
dc.subjectProteómicaes_ES
dc.subjectSíndrome de Downes_ES
dc.subjectDepresión sináptica a largo plazoes_ES
dc.subjectDiscapacidad intelectuales_ES
dc.subjectHipocampoes_ES
dc.subjectSinapsis eléctricases_ES
dc.subject.meshMedical Subject Headings::Organisms::Eukaryota::Animalses_ES
dc.subject.meshMedical Subject Headings::Anatomy::Nervous System::Neurons::Dendrites::Dendritic Spineses_ES
dc.subject.meshMedical Subject Headings::Diseases::Animal Diseases::Disease Models, Animales_ES
dc.subject.meshMedical Subject Headings::Diseases::Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Congenital Abnormalities::Chromosome Disorders::Down Syndromees_ES
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Carrier Proteins::RNA-Binding Proteins::Fragile X Mental Retardation Proteines_ES
dc.subject.meshMedical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Limbic System::Hippocampuses_ES
dc.subject.meshMedical Subject Headings::Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Genetically Modified::Mice, Transgenices_ES
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Mitochondrial Proteinses_ES
dc.subject.meshMedical Subject Headings::Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Nervous System Physiological Phenomena::Nervous System Physiological Processes::Neuronal Plasticityes_ES
dc.subject.meshMedical Subject Headings::Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biochemistry::Proteomicses_ES
dc.subject.meshMedical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Limbic System::Hippocampus::Pyramidal Cellses_ES
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, G-Protein-Coupled::Receptors, Metabotropic Glutamatees_ES
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Lactones::Macrolides::Sirolimuses_ES
dc.subject.meshMedical Subject Headings::Anatomy::Nervous System::Synapseses_ES
dc.subject.meshMedical Subject Headings::Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Nervous System Physiological Phenomena::Nervous System Physiological Processes::Neuronal Plasticity::Long-Term Synaptic Depressiones_ES
dc.subject.meshMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Micees_ES
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Proteomees_ES
dc.subject.meshMedical Subject Headings::Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Behavioral Symptoms::Depressiones_ES
dc.subject.meshMedical Subject Headings::Diseases::Nervous System Diseases::Neurologic Manifestations::Neurobehavioral Manifestations::Intellectual Disabilityes_ES
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Serine-Threonine Kinases::TOR Serine-Threonine Kinaseses_ES
dc.subject.meshMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoreticales_ES
dc.subject.meshMedical Subject Headings::Psychiatry and Psychology::Behavior and Behavior Mechanisms::Neurobehavioral Manifestations::Memory Disorderses_ES
dc.subject.meshMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Phenotypees_ES
dc.subject.meshMedical Subject Headings::Organisms::Eukaryota::Fungi::Basidiomycota::Agaricaleses_ES
dc.titlePrenatal treatment with rapamycin restores enhanced hippocampal mGluR-LTD and mushroom spine size in a Down's syndrome mouse modeles_ES
dc.typeresearch article
dc.type.hasVersionVoR
dspace.entity.typePublication

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