title: Rapamycin restores BDNF-LTP and the persistence of long-term memory in a model of Down's syndrome.
abstract: Down's syndrome (DS) is the most prevalent genetic intellectual disability. Memory deficits significantly contribute to the cognitive dysfunction in DS. Previously, we discovered that mTOR-dependent local translation, a pivotal process for some forms of synaptic plasticity, is deregulated in a DS mouse model. Here, we report that these mice exhibit deficits in both synaptic plasticity (i.e., BDNF-long term potentiation) and the persistence of spatial long-term memory. Interestingly, these deficits were fully reversible using rapamycin, a Food and Drug Administration-approved specific mTOR inhibitor; therefore, rapamycin may be a novel pharmacotherapy to improve cognition in DS.
authors.affiliation: Laboratorio de Neurociencia Celular y Plasticidad, Departamento de Fisiología, Anatomía y Biología Celular, Universidad Pablo de Olavide, E-41013 Sevilla, Spain.
authors.forename: Yuniesky
authors.initials: Y
authors.lastname: Andrade-Talavera
authors.affiliation: Departamento de Fisiología Médica y Biofísica, Universidad de Sevilla, E-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), E-41009, Sevilla, Spain.
authors.forename: Itziar
authors.initials: I
authors.lastname: Benito
authors.affiliation: Departamento de Fisiología Médica y Biofísica, Universidad de Sevilla, E-41009, Sevilla, Spain; Instituto de Biomedicina de Sevilla, IBIS/Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Casañas
authors.affiliation: Laboratorio de Neurociencia Celular y Plasticidad, Departamento de Fisiología, Anatomía y Biología Celular, Universidad Pablo de Olavide, E-41013 Sevilla, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rodríguez-Moreno
authors.affiliation: Departamento de Fisiología Médica y Biofísica, Universidad de Sevilla, E-41009, Sevilla, Spain; Instituto de Biomedicina de Sevilla, IBIS/Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain. Electronic address: mlmontesinos@us.es.
authors.forename: María Luz
authors.initials: ML
authors.lastname: Montesinos
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000503:physiopathology; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000188:drug therapy; D057567:Memory, Long-Term / Q000187:drug effects* / Q000502:physiology; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018697:Nootropic Agents / Q000494:pharmacology*; D020123:Sirolimus / Q000494:pharmacology*; D065852:Spatial Memory / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D046509:Tissue Culture Techniques
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018697:Nootropic Agents; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: BDNF-LTP; Barnes maze; ERK; MTOR; Pharmacotherapy; Rapamycin; Synaptic plasticity; Trisomy 21; Ts1Cje