| First Author | Urbano-Gámez JD | Year | 2021 |
| Journal | Mol Brain | Volume | 14 |
| Issue | 1 | Pages | 84 |
| PubMed ID | 34034796 | Mgi Jnum | J:325522 |
| Mgi Id | MGI:6713607 | Doi | 10.1186/s13041-021-00795-6 |
| Citation | Urbano-Gamez JD, et al. (2021) 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 |
| abstractText | 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. |
