| Autor: |
Urbano-Gámez JD; Departamento de Fisiología Médica Y Biofísica, Universidad de Sevilla, Av. Sánchez-Pizjuán 4, 41009, Sevilla, Spain.; Instituto de Biomedicina de Sevilla, IBIS/Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain., Casañas JJ; Departamento de Fisiología Médica Y Biofísica, Universidad de Sevilla, Av. Sánchez-Pizjuán 4, 41009, Sevilla, Spain.; Instituto de Biomedicina de Sevilla, IBIS/Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain., Benito I; Departamento de Fisiología Médica Y Biofísica, Universidad de Sevilla, Av. Sánchez-Pizjuán 4, 41009, Sevilla, Spain.; Instituto de Biomedicina de Sevilla, IBIS/Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.; Servicio de Animalario, Hospital Universitario Virgen Macarena (HUVM), 41009, Sevilla, Spain., Montesinos ML; Departamento de Fisiología Médica Y Biofísica, Universidad de Sevilla, Av. Sánchez-Pizjuán 4, 41009, Sevilla, Spain. mlmontesinos@us.es.; Instituto de Biomedicina de Sevilla, IBIS/Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain. mlmontesinos@us.es. |
| Abstrakt: |
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. |
