Prenatal treatment with rapamycin restores enhanced hippocampal mGluR-LTD and mushroom spine size in a Down's syndrome mouse model.
Mol Brain
; 14(1): 84, 2021 05 25.
Article
in En
| MEDLINE
| ID: mdl-34034796
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Down Syndrome
/
Receptors, Metabotropic Glutamate
/
Sirolimus
/
Long-Term Synaptic Depression
/
Dendritic Spines
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Mol Brain
Journal subject:
BIOLOGIA MOLECULAR
/
CEREBRO
Year:
2021
Document type:
Article
Affiliation country:
Spain