RT Journal Article
T1 Prenatal treatment with rapamycin restores enhanced hippocampal mGluR-LTD and mushroom spine size in a Down's syndrome mouse model
A1 Urbano-Gámez, Jesús David
A1 Casañas, Juan José
A1 Benito, Itziar
A1 Montesinos, María Luz
K1 mGluR-LTD
K1 mTOR
K1 Dendritic spines
K1 Proteomics
K1 Down syndrome
K1 Synaptoneurosomes
K1 Trisomy 21
K1 Long term depression
K1 Intellectual disability
K1 Hippocampus
K1 Neuronal synapse
K1 Receptores de glutamato metabotrópico
K1 Inhibidores mTOR
K1 Espinas dendríticas
K1 Proteómica
K1 Síndrome de Down
K1 Depresión sináptica a largo plazo
K1 Discapacidad intelectual
K1 Hipocampo
K1 Sinapsis eléctricas
AB 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.
PB BioMed Central, Springer Nature
YR 2021
FD 2021-05-25
LK http://hdl.handle.net/10668/4404
UL http://hdl.handle.net/10668/4404
LA en
NO 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
DS RISalud
RD Jul 31, 2025