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Memantine normalizes several phenotypic features in the Ts65Dn mouse model of down syndrome

Abstract: Ts65Dn (TS) mice exhibit several phenotypic characteristics of human Down syndrome, including an increased brain expression of amyloid-beta protein precursor (AbetaPP) and cognitive disturbances. Aberrant N-methyl-D-aspartate (NMDA) receptor signaling has been suspected in TS mice, due to an impaired generation of hippocampal long-term potentiation (LTP). Memantine, an uncompetitive NMDA receptor antagonist approved for the treatment of moderate to severe Alzheimer's disease, is known to normalize LTP and improve cognition in transgenic mice with high brain levels of AbetaPP and amyloid-beta protein. It has recently been demonstrated that acute injections of memantine rescue performance deficits of TS mice on a fear conditioning test. Here we show that oral treatment of aged TS mice with a clinically relevant dose of memantine (30 mg/kg/day for 9 weeks) improved spatial learning in the water maze task and slightly reduced brain AbetaPP levels. We also found that TS mice exhibited a significantly reduced granule cell count and vesicular glutamate transporter-1 (VGLUT1) labeling compared to disomic control mice. After memantine treatment, the levels of hippocampal VGLUT1 were significantly increased, reaching the levels observed in vehicle treated-control animals. Memantine did not significantly affect granule cell density. These data indicate that memantine may normalize several phenotypic abnormalities in TS mice, many of which--such as impaired cognition--are also associated with Down syndrome and Alzheimer's disease.

 Autoría: Rueda N., Llorens-Martín M., Flórez J., Valdizán E., Banerjee P., Trejo J.L., Martínez-Cué C.,

 Fuente: Journal of Alzheimer's Disease, 2010, 21(1), 277-290

 Editorial: IOS Press

 Año de publicación: 2010

 Nº de páginas: 14

 Tipo de publicación: Artículo de Revista

 DOI: 10.3233/JAD-2010-100240

 ISSN: 1387-2877,1875-8908

 Url de la publicación: http://dx.doi.org/10.3233/JAD-2010-100240

Autoría

LLORENS-MARTÍN, MARÍA

JESUS FLOREZ BELEDO

ELSA MARIA VALDIZAN RUIZ

BANERJEE, PRADEEP

TREJO, JOSE LUIS