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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.
Fuente: Journal of Pineal Research, 2014, 56, 51-61
Publisher: Blackwell Publishing Ltd
Year of publication: 2014
No. of pages: 11
Publication type: Article
DOI: 10.1111/jpi.12097
ISSN: 0742-3098,1600-079X
Spanish project: PSI2012-33652
Consult in UCrea Read publication
ANDREA CORRALES PARDO
REBECA VIDAL CASADO
SUSANA GARCIA CERRO
VERONICA VIDAL SANCHEZ
PAULA MARTINEZ FERNANDEZ
MARIA EVA GARCIA IGLESIAS
JESUS FLOREZ BELEDO
EMILIO JOSE SANCHEZ BARCELO
CARMEN MARTINEZ-CUE PESINI
NOEMI RUEDA REVILLA
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