Altered hippocampal transcript profile accompanies an age-related spatial memory deficit in mice
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We have carried out a global survey of age-related changes in mRNA levels in the C57BL/6NIA mouse hippocampus and found a difference in the hippocampal gene expression profile between 2-month-old young mice and 15-month-old middle-aged mice correlated with an age-related cognitive deficit in hippocampal-based explicit memory formation. Middle-aged mice displayed a mild but specific deficit in spatial memory in the Morris water maze. By using Affymetrix GeneChip microarrays, we found a distinct pattern of age-related change, consisting mostly of gene overexpression in the middle-aged mice, suggesting that the induction of negative regulators in the middle-aged hippocampus could be involved in impairment of learning. Interestingly, we report changes in transcript levels for genes that could affect synaptic plasticity. Those changes could be involved in the memory deficits we observed in the 15-month-old mice. In agreement with previous reports, we also found altered expression in genes related to inflammation, protein processing, and oxidative stress.
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Accumulated pro-inflammation and oxidative stress in the brain, often observed in aged brains and aged microglia, could cause sustained suppression of Trem2 expression and thus an impairment of TREM2-dependent microglial functions.
“accumulated pro-inflammation and oxidative stress in the brain, which is often observed in aged brains and aged microglia (90–94), could cause sustained suppression of Trem2 expression and thus an impairment of TREM2-dependent microglial functions.”
From <i>Trem2</i> promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions (2020) · cites this paper as [93]
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- Authors
- Verbitsky, M., Yonan, A. L., Malleret, G., Kandel, E. R., Gilliam, T. C., & Pavlidis, P.
- Affiliations
- Howard Hughes Medical Institute (US)
- Venue
- Learning & Memory
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2004-05
- Volume
- 11
- Issue
- 3
- Pages
- 253-260
- ISSN
- 1072-0502 (ISSN-L)
- 1549-5485
- PMC
- PMC419727
- OpenAlex
- W2039296833
- Cited by
- 158
- References
- 72
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 4 · 2023: 10 · 2022: 6 · 2021: 12 · 2020: 4 · 2019: 9 · 2018: 5 · 2017: 10 · 2016: 4 · 2015: 7 · 2014: 6 · 2013: 9 · 2012: 11
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Learning & Memory (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- hippocampus, aging, spatial memory, gene expression profiles, declarative memory, synaptic plasticity, inflammation, oxidative stress, protein processing, learning disabilities, age-related cognitive decline
- MeSH terms
- Aging, Animals, Discrimination Learning, Gene Expression Regulation, Hippocampus, Learning Disabilities, Memory Disorders, Mice, Inbred C57BL, RNA, Messenger, Space Perception, Spatial Behavior, Maze Learning, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Mice
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