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 Detalle_Publicacion

Chronic melatonin treatment rescues electrophysiological and neuromorphological deficits in a mouse model of Down syndrome

Abstract: The Ts65Dn mouse (TS), the most commonly used model of Down syndrome (DS), exhibits several key phenotypic characteristics of this condition. In particular, these animals present hypocellularity in different areas of their CNS due to impaired neurogenesis and have alterations in synaptic plasticity that compromise their cognitive performance. In addition, increases in oxidative stress during adulthood contribute to the age-related progression of cognitive and neuronal deterioration. We have previously demonstrated that chronic melatonin treatment improves learning and memory and reduces cholinergic neurodegeneration in TS mice. However, the molecular and physiological mechanisms that mediate these beneficial cognitive effects are not yet fully understood. In this study, we analyzed the effects of chronic melatonin treatment on different mechanisms that have been proposed to underlie the cognitive impairments observed in TS mice: reduced neurogenesis, altered synaptic plasticity, enhanced synaptic inhibition and oxidative damage. Chronic melatonin treatment rescued both impaired adult neurogenesis and the decreased density of hippocampal granule cells in trisomic mice. In addition, melatonin administration reduced synaptic inhibition in TS mice by increasing the density and/or activity of glutamatergic synapses in the hippocampus. These effects were accompanied by a full recovery of hippocampal LTP in trisomic animals. Finally, melatonin treatment decreased the levels of lipid peroxidation in the hippocampus of TS mice. These results indicate that the cognitive-enhancing effects of melatonin in adult TS mice could be mediated by the normalization of their electrophysiological and neuromorphological abnormalities and suggest that melatonin represents an effective treatment in retarding the progression of DS neuropathology.

Otras publicaciones de la misma revista o congreso con autores/as de la Universidad de Cantabria

 Fuente: J. Pineal Res. 2014; 56:51–61

Editorial: Blackwell Publishing Ltd

 Año de publicación: 2014

Nº de páginas: 11

Tipo de publicación: Artículo de Revista

 DOI: 10.1111/jpi.12097

ISSN: 0742-3098,1600-079X

Proyecto español: PSI2012-33652

Autores/as

ANDREA CORRALES PARDO

REBECA VIDAL CASADO

SUSANA GARCIA CERRO

VERONICA VIDAL SANCHEZ

PAULA MARTINEZ FERNANDEZ

JESUS FLOREZ BELEDO

EMILIO JOSE SANCHEZ BARCELO