ArticleMolecular & cellular proteomics : MCP2014
Hippocampal extracellular matrix levels and stochasticity in synaptic protein expression increase with age and are associated with age-dependent cognitive decline.
Article in Molecular & cellular proteomics : MCP, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
30 citing papers in PubMed, 57 citations in OpenAlex.
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- Stochastic Nanoscale Biophysical Cues as a Basis for the Induction of Glioblastoma-Like Transcriptional Programs in Astrocytes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Midbrain extracellular matrix and microglia are associated with cognition in aging mice.Nature communications · 2025Article
- Increased levels of extracellular matrix proteins associated with extracellular vesicles from brains of aged mice.Aging cell · 2025Article
- Role of folate receptor α in the partial rejuvenation of dentate gyrus cells: Improvement of cognitive function in 21-month-old aged mice.Scientific reports · 2024Article
- Neuronal TIMP2 regulates hippocampus-dependent plasticity and extracellular matrix complexity.Molecular psychiatry · 2023Article
- Insights gained from single-cell RNA analysis of murine endothelial cells in aging hearts.Heliyon · 2023Article
- Microglia in Alzheimer's disease: pathogenesis, mechanisms, and therapeutic potentials.Frontiers in aging neuroscience · 2023Review
- Matrix disequilibrium in Alzheimer's disease and conditions that increase Alzheimer's disease risk.Frontiers in neuroscience · 2023Review
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- Regulation of microglia phagocytosis and potential involvement of exercise.Frontiers in cellular neuroscience · 2022Review
- Single-nucleus transcriptomic landscape of primate hippocampal aging.Protein & cell · 2021Article
- An Extracellular Perspective on CNS Maturation: Perineuronal Nets and the Control of Plasticity.International journal of molecular sciences · 2021Review
- A Shift in Tissue Stiffness During Hippocampal Maturation Correlates to the Pattern of Neurogenesis and Composition of the Extracellular Matrix.Frontiers in aging neuroscience · 2021Article
- Compromised Astrocyte Swelling/Volume Regulation in the Hippocampus of the Triple Transgenic Mouse Model of Alzheimer's Disease.Frontiers in aging neuroscience · 2021Article
- Article
- Identification of Potential Interacting Proteins With the Extracellular Loops of the Neuronal Glycoprotein M6a by TMT/MS.Frontiers in synaptic neuroscience · 2020Article
- Increased expression of heme-binding protein 1 early in Alzheimer's disease is linked to neurotoxicity.eLife · 2019Article
- Age-related behavioral changes from young to old age in male mice of a C57BL/6J strain maintained under a genetic stability program.Neuropsychopharmacology reports · 2019Article
- "Teaching old dogs new tricks": targeting neural extracellular matrix for normal and pathological aging-related cognitive decline.Neural regeneration research · 2019Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Age-related cognitive decline is a serious health concern in our aging society. Decreased cognitive function observed during healthy brain aging is most likely caused by changes in brain connectivity and synaptic dysfunction in particular brain regions. Here we show that aged C57BL/6J wild-type mice have hippocampus-dependent spatial memory impairments. To identify the molecular mechanisms that are relevant to these memory deficits, we investigated the temporal profile of mouse hippocampal synaptic proteome changes at 20, 40, 50, 60, 70, 80, 90, and 100 weeks of age. Extracellular matrix proteins were the only group of proteins that showed robust and progressive up-regulation over time. This was confirmed by immunoblotting and histochemical analysis, which indicated that the increased levels of hippocampal extracellular matrix might limit synaptic plasticity as a potential cause of age-related cognitive decline. In addition, we observed that stochasticity in synaptic protein expression increased with age, in particular for proteins that were previously linked with various neurodegenerative diseases, whereas low variance in expression was observed for proteins that play a basal role in neuronal function and synaptic neurotransmission. Together, our findings show that both specific changes and increased variance in synaptic protein expression are associated with aging and may underlie reduced synaptic plasticity and impaired cognitive performance in old age.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.