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Title: Prenatal treatment with rapamycin restores enhanced hippocampal mGluR-LTD and mushroom spine size in a Down's syndrome mouse model.
Authors: Urbano-Gámez, Jesús David
Casañas, Juan José
Benito, Itziar
Montesinos, María Luz
Keywords: Dendritic spines;Down syndrome;Proteomics;Synaptoneurosomes;Trisomy 21;mGluR-LTD;mTOR
metadata.dc.subject.mesh: Animals
Dendritic Spines
Disease Models, Animal
Down Syndrome
Fragile X Mental Retardation Protein
Long-Term Synaptic Depression
Mice, Transgenic
Mitochondrial Proteins
Neuronal Plasticity
Pyramidal Cells
Receptors, Metabotropic Glutamate
Issue Date: 25-May-2021
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.
metadata.dc.identifier.doi: 10.1186/s13041-021-00795-6
Appears in Collections:Producción 2020

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