@article{10902/30878,
year = {2013},
url = {https://hdl.handle.net/10902/30878},
abstract = {Down syndrome (DS) is associated with neurological complications, including cognitive deficits that lead to impairment in intellectual functioning. Increased GABA-mediated inhibition has been proposed as a mechanism underlying deficient cognition in the Ts65Dn (TS) mouse model of DS. We show that chronic treatment of these mice with RO4938581 (3-bromo-10-(difluoromethyl)-9H-benzo[f]imidazo[1,5-a][1,2,4]triazolo[1,5-d][1,4]diazepine), a selective GABAA alfa5 negative allosteric modulator (NAM), rescued their deficits in spatial learning and memory, hippocampal synaptic plasticity, and adult neurogenesis. We also show that RO4938581 normalized the high density of GABAergic synapse markers in the molecular layer of the hippocampus of TS mice. In addition, RO4938581 treatment suppressed the hyperactivity observed in TS mice without inducing anxiety or altering their motor abilities. These data demonstrate that reducing GABAergic inhibition with RO4938581 can reverse functional and neuromorphological deficits of TS mice by facilitating brain plasticity and support the potential therapeutic use of selective GABAA alfa5 NAMs to treat cognitive dysfunction in DS.},
organization = {This work was supported by F. Hoffmann-La Roche, the Jerome Lejeune Foundation, and Spanish Ministry of
Education and Science Grants BFU2008-04397 and BFU2011-24755. We thank E. García Iglesias, M. Cárcamo, and R. Madureira for their technical assistance, Drs. T. Ballard and G. Trube for helpful discussions, and S. Ortega, S. Gradari, and P. Pérez-Domper for advice on experiments.},
publisher = {Society for Neuroscience},
publisher = {Journal of Neuroscience, 2013, 33 (9), 3953-3966},
title = {Reducing GABAA [alfa]5 receptor-mediated inhibition rescues functional and neuromorphological deficits in a mouse model of Down syndrome},
author = {Martínez-Cué, Carmen and Martínez Fernández, Paula and Rueda Revilla, Noemí and Vidal Casado, Rebeca and García Cerro, Susana and Vidal Sánchez, Verónica and Corrales Pardo, Andrea and Montero Simón, Juan Antonio and Pazos Carro, Ángel and Florez Beledo, Jesús and Rodolfo Gasser and Andrew W. Thomas and Michael Honer and Frédéric Knoflach and José Luis Trejo and Joseph G. Wettstein and María-Clemencia Hernández},
}