Early and sustained altered expression of aging-related genes in young 3xTg-AD mice
Open accessAbstract
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.
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Recent evidence indicates that the 3xTg-AD displays early changes in neuronal network and synaptic function, before the appearance of cognitive and physiological alterations.
“Nevertheless, recent evidence indicates that the 3xTg-AD displays early changes in neuronal network and synaptic function, before the appearance of cognitive and physiological alterations (Chakroborty et al., 2012; Gatta et al., 2014; Kazim et al., 2017).”
From Early stage alterations in white matter and decreased functional interhemispheric hippocampal connectivity in the 3xTg mouse model of Alzheimer’s disease. (2019) · cites this paper as Gatta et al., 2014
The Discussion section “Dendrite formation, synaptic plasticity, and memory” reports early changes in 3xTg-AD transcripts implicated in synaptic functioning. The paper measures gene expression, however, not neuronal-network or synaptic function directly, and it does not establish that these changes precede cognitive and physiological alterations (no page numbers provided). (LLM, conf=0.84)
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- Authors
- Gatta, V, D'Aurora, M., Granzotto, A., Stuppia, L., & Sensi, S. L.
- Affiliations
- University of Chieti-Pescara (IT)
- University of California, Irvine (US)
- Corresponding author
- Sensi, S L
- Venue
- Cell Death & Disease
- Published
- 2014-02-13
- Volume
- 5
- Issue
- 2
- Pages
- e1054-e1054
- ISSN
- 2041-4889 (ISSN-L)
- PMC
- PMC3944230
- OpenAlex
- W2071462548
- Cited by
- 44
- References
- 69
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 3 · 2022: 3 · 2021: 2 · 2020: 7 · 2019: 7 · 2018: 3 · 2017: 3 · 2016: 3 · 2015: 3 · 2014: 4
- FWCI
- 2.89
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- www.springer.com/tdm (unspecified)
- Locations
- Cell Death and Disease (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, 3xTg-AD mice, aging, gene expression profiling, hippocampus, age-related gene expression, amyloid precursor protein, presenilin 1, tau hyperphosphorylation, neuronal cell death, autophagy, mitochondrial function, calcium homeostasis, neuroinflammation, dendritic spine formation, synaptic function, cognitive decline
- MeSH terms
- Age Factors, Aging, Alzheimer Disease, Animals, Disease Models, Animal, Female, Gene Expression Regulation, Hippocampus, Humans, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Phenotype, Time Factors, Reproducibility of Results, Cluster Analysis, Polymerase Chain Reaction, Amyloid beta-Protein Precursor, tau Proteins, Genetic Predisposition to Disease, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Mice, Gene Regulatory Networks, Presenilin-1, Mice, 129 Strain
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