Urbano-Gámez, Jesús DavidCasañas, Juan JoséBenito, ItziarMontesinos, María Luz2022-11-252022-11-252021-05-25Urbano-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):84http://hdl.handle.net/10668/4404Down 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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/mGluR-LTDmTORDendritic spinesProteomicsDown syndromeSynaptoneurosomesTrisomy 21Long term depressionIntellectual disabilityHippocampusNeuronal synapseReceptores de glutamato metabotrópicoInhibidores mTOREspinas dendríticasProteómicaSíndrome de DownDepresión sináptica a largo plazoDiscapacidad intelectualHipocampoSinapsis eléctricasMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Anatomy::Nervous System::Neurons::Dendrites::Dendritic SpinesMedical Subject Headings::Diseases::Animal Diseases::Disease Models, AnimalMedical Subject Headings::Diseases::Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Congenital Abnormalities::Chromosome Disorders::Down SyndromeMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Carrier Proteins::RNA-Binding Proteins::Fragile X Mental Retardation ProteinMedical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Limbic System::HippocampusMedical Subject Headings::Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Genetically Modified::Mice, TransgenicMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Mitochondrial ProteinsMedical Subject Headings::Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Nervous System Physiological Phenomena::Nervous System Physiological Processes::Neuronal PlasticityMedical Subject Headings::Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biochemistry::ProteomicsMedical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Limbic System::Hippocampus::Pyramidal CellsMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, G-Protein-Coupled::Receptors, Metabotropic GlutamateMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Lactones::Macrolides::SirolimusMedical Subject Headings::Anatomy::Nervous System::SynapsesMedical Subject Headings::Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Nervous System Physiological Phenomena::Nervous System Physiological Processes::Neuronal Plasticity::Long-Term Synaptic DepressionMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::MiceMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::ProteomeMedical Subject Headings::Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Behavioral Symptoms::DepressionMedical Subject Headings::Diseases::Nervous System Diseases::Neurologic Manifestations::Neurobehavioral Manifestations::Intellectual DisabilityMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Serine-Threonine Kinases::TOR Serine-Threonine KinasesMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, TheoreticalMedical Subject Headings::Psychiatry and Psychology::Behavior and Behavior Mechanisms::Neurobehavioral Manifestations::Memory DisordersMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::PhenotypeMedical Subject Headings::Organisms::Eukaryota::Fungi::Basidiomycota::Agaricalesresearch article34034796open access10.1186/s13041-021-00795-61756-6606PMC8152312