Article
Prenatal treatment with rapamycin restores enhanced hippocampal mGluR‑LTD and mushroom spine size in a Down’s syndrome mouse model
Author/s | Urbano Gámez, Jesús David
Casañas, Juan José Benito, Itziar Montesinos, María Luz |
Department | Universidad de Sevilla. Departamento de Ingeniería Eléctrica |
Publication Date | 2021 |
Deposit Date | 2022-09-07 |
Published in |
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Abstract | Down syndrome (DS) is the most frequent genetic cause of intellectual disability including hippocampal-dependent
memory defcits. We have previously reported hippocampal mTOR (mammalian target of rapamycin) hyperactiva‑
tion, ... Down syndrome (DS) is the most frequent genetic cause of intellectual disability including hippocampal-dependent memory defcits. We have previously reported hippocampal mTOR (mammalian target of rapamycin) hyperactiva‑ tion, and related plasticity as well as memory defcits in Ts1Cje mice, a DS experimental model. Here we character‑ ize 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 efect on both phenotypes, supporting the therapeutic potential of rapamycin/rapalogs for DS intellectual disability |
Funding agencies | European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER) Fondation Jérôme Lejeune (Francia) |
Project ID. | P12-CTS-1818
SAF2015-65032-R |
Citation | Urbano Gámez, J.D., Casañas, J.J., Benito, I. y Montesinos, M.L. (2021). Prenatal treatment with rapamycin restores enhanced hippocampal mGluR‑LTD and mushroom spine size in a Down’s syndrome mouse model. Molecular Brain, 14 (1), Article number 84. |
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