• Login
    View Item 
    •   UCrea
    • UCrea Investigación
    • Departamento de Fisiología y Farmacología
    • D16 Proyectos de investigación
    • View Item
    •   UCrea
    • UCrea Investigación
    • Departamento de Fisiología y Farmacología
    • D16 Proyectos de investigación
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Decreasing the Expression of GABAA[alfa]5 Subunit-Containing Receptors Partially Improves Cognitive, Electrophysiological, and Morphological Hippocampal Defects in the Ts65Dn Model of Down Syndrome

    View/Open
    DecreasingTheExpress ... (786.2Kb)
    Identificadores
    URI: http://hdl.handle.net/10902/13706
    DOI: 10.1007/s12035-017-0675-3
    ISSN: 0893-7648
    ISSN: 1559-1182
    Compartir
    RefworksMendeleyBibtexBase
    Estadísticas
    View Usage Statistics
    Google Scholar
    Full record
    Show full item record
    Author
    Vidal Sánchez, Verónica; García Cerro, Susana; Martínez Fernández, Paula; Corrales Pardo, Andrea; Lantigua Romero, Sara; Vidal Casado, Rebeca; Rueda Revilla, Noemí; Ozmen, Laurence; Hernández, Maria Clemencia; Martínez-Cué, Carmen
    Date
    2018-06
    Derechos
    © Springer. The final publication is available at Springer via http://dx.doi.org/10.1007/s12035-017-0675-3
    Publicado en
    Molecular Neurobiology June 2018, Volume 55, Issue 6, pp 4745-4762
    Publisher
    Springer
    Enlace a la publicación
    https://dx.doi.org/10.1007/s12035-017-0675-3
    Palabras clave
    GABAA
    α5 subunit
    Down Syndrome
    Over-inhibition
    Ts65Dn mice
    Cognition
    Abstract:
    Trisomy 21 or Down syndrome (DS) is the most common cause of intellectual disability of a genetic origin. The Ts65Dn (TS) mouse, which is the most commonly used and best-characterized mouse model of DS, displays many of the cognitive, neuromorphological, and biochemical anomalies that are found in the human condition. One of the mechanisms that have been proposed to be responsible for the cognitive deficits in this mouse model is impaired GABAmediated inhibition. Because of the well-known modulatory role of GABAA ?5 subunit-containing receptors in cognitive processes, these receptors are considered to be potential targets for improving the intellectual disability in DS. The chronic administration of GABAA ?5-negative allosteric modulators has been shown to be procognitive without anxiogenic or proconvulsant side effects. In the present study, we use a genetic approach to evaluate the contribution of GABAA ?5 subunit-containing receptors to the cognitive, electrophysiological, and neuromorphological deficits in TS mice.We show that reducing the expression of GABAA ?5 receptors by deleting one or two copies of the Gabra5 gene in TS mice partially ameliorated the cognitive impairments, improved longterm potentiation, enhanced neural differentiation and maturation, and normalized the density of the GABAergic synapse markers. Reducing the gene dosage of Gabra5 in TS mice did not induce motor alterations and anxiety or affect the viability of the mice. Our results provide further evidence of the role of GABAA ?5 receptor-mediated inhibition in cognitive impairment in the TS mouse model of DS.
    Collections to which it belong
    • D16 Proyectos de investigación [38]
    • D16 Artículos [118]
    • D55 Artículos [78]
    • D55 Proyectos de investigación [32]

    UNIVERSIDAD DE CANTABRIA

    Repositorio realizado por la Biblioteca Universitaria utilizando DSpace software
    Contact Us | Send Feedback
    Metadatos sujetos a:licencia de Creative Commons Reconocimiento 3.0 España
     

     

    Browse

    All of UCreaCommunities and CollectionsBy Issue DateAuthorsTitlesSubjectsUC AuthorsThis CollectionBy Issue DateAuthorsTitlesSubjectsUC Authors

    My Account

    LoginRegister

    Statistics

    View Usage Statistics
    About UCrea
    What is UcreaGuide of self-archivingThesis archiveOpen accessCopyright guideInstitutional policy
    Thinks in open
    Piensa en abierto
    Share

    UNIVERSIDAD DE CANTABRIA

    Repositorio realizado por la Biblioteca Universitaria utilizando DSpace software
    Contact Us | Send Feedback
    Metadatos sujetos a:licencia de Creative Commons Reconocimiento 3.0 España