Publication: Prenatal treatment with rapamycin restores enhanced hippocampal mGluR-LTD and mushroom spine size in a Down's syndrome mouse model
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Date
2021-05-25
Authors
Urbano-Gámez, Jesús David
Casañas, Juan José
Benito, Itziar
Montesinos, María Luz
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Publisher
BioMed Central, Springer Nature
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Abstract
Down 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.
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MeSH Terms
Medical Subject Headings::Organisms::Eukaryota::Animals
Medical Subject Headings::Anatomy::Nervous System::Neurons::Dendrites::Dendritic Spines
Medical Subject Headings::Diseases::Animal Diseases::Disease Models, Animal
Medical Subject Headings::Diseases::Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Congenital Abnormalities::Chromosome Disorders::Down Syndrome
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Carrier Proteins::RNA-Binding Proteins::Fragile X Mental Retardation Protein
Medical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Limbic System::Hippocampus
Medical Subject Headings::Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Genetically Modified::Mice, Transgenic
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Mitochondrial Proteins
Medical Subject Headings::Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Nervous System Physiological Phenomena::Nervous System Physiological Processes::Neuronal Plasticity
Medical Subject Headings::Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biochemistry::Proteomics
Medical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Limbic System::Hippocampus::Pyramidal Cells
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, G-Protein-Coupled::Receptors, Metabotropic Glutamate
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Lactones::Macrolides::Sirolimus
Medical Subject Headings::Anatomy::Nervous System::Synapses
Medical Subject Headings::Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Nervous System Physiological Phenomena::Nervous System Physiological Processes::Neuronal Plasticity::Long-Term Synaptic Depression
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Proteome
Medical Subject Headings::Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Behavioral Symptoms::Depression
Medical Subject Headings::Diseases::Nervous System Diseases::Neurologic Manifestations::Neurobehavioral Manifestations::Intellectual Disability
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Serine-Threonine Kinases::TOR Serine-Threonine Kinases
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical
Medical Subject Headings::Psychiatry and Psychology::Behavior and Behavior Mechanisms::Neurobehavioral Manifestations::Memory Disorders
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Phenotype
Medical Subject Headings::Organisms::Eukaryota::Fungi::Basidiomycota::Agaricales
Medical Subject Headings::Anatomy::Nervous System::Neurons::Dendrites::Dendritic Spines
Medical Subject Headings::Diseases::Animal Diseases::Disease Models, Animal
Medical Subject Headings::Diseases::Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Congenital Abnormalities::Chromosome Disorders::Down Syndrome
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Carrier Proteins::RNA-Binding Proteins::Fragile X Mental Retardation Protein
Medical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Limbic System::Hippocampus
Medical Subject Headings::Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Genetically Modified::Mice, Transgenic
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Mitochondrial Proteins
Medical Subject Headings::Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Nervous System Physiological Phenomena::Nervous System Physiological Processes::Neuronal Plasticity
Medical Subject Headings::Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biochemistry::Proteomics
Medical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Limbic System::Hippocampus::Pyramidal Cells
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, G-Protein-Coupled::Receptors, Metabotropic Glutamate
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Lactones::Macrolides::Sirolimus
Medical Subject Headings::Anatomy::Nervous System::Synapses
Medical Subject Headings::Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Nervous System Physiological Phenomena::Nervous System Physiological Processes::Neuronal Plasticity::Long-Term Synaptic Depression
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Proteome
Medical Subject Headings::Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Behavioral Symptoms::Depression
Medical Subject Headings::Diseases::Nervous System Diseases::Neurologic Manifestations::Neurobehavioral Manifestations::Intellectual Disability
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Serine-Threonine Kinases::TOR Serine-Threonine Kinases
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical
Medical Subject Headings::Psychiatry and Psychology::Behavior and Behavior Mechanisms::Neurobehavioral Manifestations::Memory Disorders
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Phenotype
Medical Subject Headings::Organisms::Eukaryota::Fungi::Basidiomycota::Agaricales
DeCS Terms
CIE Terms
Keywords
mGluR-LTD, mTOR, Dendritic spines, Proteomics, Down syndrome, Synaptoneurosomes, Trisomy 21, Long term depression, Intellectual disability, Hippocampus, Neuronal synapse, Receptores de glutamato metabotrópico, Inhibidores mTOR, Espinas dendríticas, Proteómica, Síndrome de Down, Depresión sináptica a largo plazo, Discapacidad intelectual, Hipocampo, Sinapsis eléctricas
Citation
Urbano-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):84