title: Principal Component Analysis of the Effects of Environmental Enrichment and (-)-epigallocatechin-3-gallate on Age-Associated Learning Deficits in a Mouse Model of Down Syndrome.
abstract: Down syndrome (DS) individuals present increased risk for Alzheimer's disease (AD) neuropathology and AD-type dementia. Here, we investigated the use of green tea extracts containing (-)-epigallocatechin-3-gallate (EGCG), as co-adjuvant to enhance the effects of environmental enrichment (EE) in Ts65Dn mice, a segmental trisomy model of DS that partially mimics DS/AD pathology, at the age of initiation of cognitive decline. Classical repeated measures ANOVA showed that combined EE-EGCG treatment was more efficient than EE or EGCG alone to improve specific spatial learning related variables. Using principal component analysis (PCA) we found that several spatial learning parameters contributed similarly to a first PC and explained a large proportion of the variance among groups, thus representing a composite learning measure. This PC1 revealed that EGCG or EE alone had no significant effect. However, combined EE-EGCG significantly ameliorated learning alterations of middle age Ts65Dn mice. Interestingly, PCA revealed an increased variability along learning sessions with good and poor learners in Ts65Dn, and this stratification did not disappear upon treatments. Our results suggest that combining EE and EGCG represents a viable therapeutic approach for amelioration of age-related cognitive decline in DS, although its efficacy may vary across individuals.
authors.affiliation: Systems Biology Program, Cellular and Systems Neurobiology, Centre for Genomic Regulation, The Barcelona Institute of Science and Technology Barcelona, Spain ; Centre for Genomic Regulation, Universitat Pompeu Fabra Barcelona, Spain.
authors.forename: Silvina
authors.initials: S
authors.lastname: Catuara-Solarz
authors.affiliation: Systems Biology Program, Cellular and Systems Neurobiology, Centre for Genomic Regulation, The Barcelona Institute of Science and Technology Barcelona, Spain ; Centre for Genomic Regulation, Universitat Pompeu Fabra Barcelona, Spain ; Bioinformatics and Genomics Program, Comparative Bioinformatics, Centre for Genomic Regulation, Barcelona Institute of Science and Technology Barcelona, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Espinosa-Carrasco
authors.affiliation: Centre for Genomic Regulation, Universitat Pompeu Fabra Barcelona, Spain ; Bioinformatics and Genomics Program, Comparative Bioinformatics, Centre for Genomic Regulation, Barcelona Institute of Science and Technology Barcelona, Spain.
authors.forename: Ionas
authors.initials: I
authors.lastname: Erb
authors.affiliation: Neurosciences Research Program, Human Pharmacology and Clinical Neurosciences Research Group, IMIM (Hospital del Mar Medical Research Institute) Barcelona, Spain ; Department of Statistics and Operations Research, Universitat Politècnica de Catalunya/BARCELONATECH Barcelona, Spain.
authors.forename: Klaus
authors.initials: K
authors.lastname: Langohr
authors.affiliation: Centre for Genomic Regulation, Universitat Pompeu Fabra Barcelona, Spain ; Bioinformatics and Genomics Program, Comparative Bioinformatics, Centre for Genomic Regulation, Barcelona Institute of Science and Technology Barcelona, Spain.
authors.forename: Cedric
authors.initials: C
authors.lastname: Notredame
authors.affiliation: Bioinformatics and Genomics Program, Comparative Bioinformatics, Centre for Genomic Regulation, Barcelona Institute of Science and Technology Barcelona, Spain ; Centre for Research in Environmental Epidemiology Barcelona, Spain ; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública Barcelona, Spain.
authors.forename: Juan R
authors.initials: JR
authors.lastname: Gonzalez
authors.affiliation: Systems Biology Program, Cellular and Systems Neurobiology, Centre for Genomic Regulation, The Barcelona Institute of Science and Technology Barcelona, Spain ; Centre for Genomic Regulation, Universitat Pompeu Fabra Barcelona, Spain ; Centro de Investigación Biomédica en Red de Enfermedades Raras Barcelona, Spain.
authors.forename: Mara
authors.initials: M
authors.lastname: Dierssen
keywords: (-)-epigallocatechin-3-gallate; Down syndrome; Morris water maze; aging; principal component analysis