%0 Journal Article
%A Urbano-Gámez, Jesús David
%A Casañas, Juan José
%A Benito, Itziar
%A Montesinos, María Luz
%T Prenatal treatment with rapamycin restores enhanced hippocampal mGluR-LTD and mushroom spine size in a Down's syndrome mouse model
%D 2021
%U http://hdl.handle.net/10668/4404
%X 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.
%K mGluR-LTD
%K mTOR
%K Dendritic spines
%K Proteomics
%K Down syndrome
%K Synaptoneurosomes
%K Trisomy 21
%K Long term depression
%K Intellectual disability
%K Hippocampus
%K Neuronal synapse
%K Receptores de glutamato metabotrópico
%K Inhibidores mTOR
%K Espinas dendríticas
%K Proteómica
%K Síndrome de Down
%K Depresión sináptica a largo plazo
%K Discapacidad intelectual
%K Hipocampo
%K Sinapsis eléctricas
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