title: Early and sustained altered expression of aging-related genes in young 3xTg-AD mice.
abstract: Alzheimer's disease (AD) is a multifactorial neurological condition associated with a genetic profile that is still not completely understood. In this study, using a whole gene microarray approach, we investigated age-dependent gene expression profile changes occurring in the hippocampus of young and old transgenic AD (3xTg-AD) and wild-type (WT) mice. The aim of the study was to assess similarities between aging- and AD-related modifications of gene expression and investigate possible interactions between the two processes. Global gene expression profiles of hippocampal tissue obtained from 3xTg-AD and WT mice at 3 and 12 months of age (m.o.a.) were analyzed by hierarchical clustering. Interaction among transcripts was then studied with the Ingenuity Pathway Analysis (IPA) software, a tool that discloses functional networks and/or pathways associated with sets of specific genes of interest. Cluster analysis revealed the selective presence of hundreds of upregulated and downregulated transcripts. Functional analysis showed transcript involvement mainly in neuronal death and autophagy, mitochondrial functioning, intracellular calcium homeostasis, inflammatory response, dendritic spine formation, modulation of synaptic functioning, and cognitive decline. Thus, overexpression of AD-related genes (such as mutant APP, PS1, and hyperphosphorylated tau, the three genes that characterize our model) appears to favor modifications of additional genes that are involved in AD development and progression. The study also showed overlapping changes in 3xTg-AD at 3 m.o.a. and WT mice at 12 m.o.a., thereby suggesting altered expression of aging-related genes that occurs earlier in 3xTg-AD mice.
authors: 1] Functional Genetics Unit, Center of Excellence on Aging (CeSI), Chieti, Italy [2] Department of Psychological Sciences, 'G. d'Annunzio' University, Chieti, Italy.
authors: V
authors: V
authors: Gatta
authors: 1] Functional Genetics Unit, Center of Excellence on Aging (CeSI), Chieti, Italy [2] Department of Neuroscience and Imaging, 'G. d'Annunzio' University, Chieti, Italy.
authors: M
authors: M
authors: D'Aurora
authors: Molecular Neurology Unit, Center of Excellence on Aging (CeSI), Chieti, Italy.
authors: A
authors: 0000000191814373
authors: A
authors: Granzotto
authors: 1] Functional Genetics Unit, Center of Excellence on Aging (CeSI), Chieti, Italy [2] Department of Psychological Sciences, 'G. d'Annunzio' University, Chieti, Italy.
authors: L
authors: L
authors: Stuppia
authors: 1] Department of Neuroscience and Imaging, 'G. d'Annunzio' University, Chieti, Italy [2] Molecular Neurology Unit, Center of Excellence on Aging (CeSI), Chieti, Italy [3] Departments of Neurology and Pharmacology, University of California-Irvine, Irvine, CA, USA [4] Institute for Memory Impairments and Neurological Disorders, University of California-Irvine, Irvine, CA, USA.
authors: S L
authors: SL
authors: Sensi
mesh_terms: D000367:Age Factors; D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D016000:Cluster Analysis; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D020022:Genetic Predisposition to Disease; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D016133:Polymerase Chain Reaction; D053764:Presenilin-1 / Q000235:genetics* / Q000378:metabolism; D015203:Reproducibility of Results; D013997:Time Factors; D016875:tau Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1; D016875:tau Proteins