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Acute stress increases interstitial fluid amyloid-β via corticotropin-releasing factor and neuronal activity
Open accessAbstract
Aggregation of the amyloid-beta (Abeta) peptide in the extracellular space of the brain is critical in the pathogenesis of Alzheimer's disease. Abeta is produced by neurons and released into the brain interstitial fluid (ISF), a process regulated by synaptic activity. To determine whether behavioral stressors can regulate ISF Abeta levels, we assessed the effects of chronic and acute stress paradigms in amyloid precursor protein transgenic mice. Isolation stress over 3 months increased Abeta levels by 84%. Similarly, acute restraint stress increased Abeta levels over hours. Exogenous corticotropin-releasing factor (CRF) but not corticosterone mimicked the effects of acute restraint stress. Inhibition of endogenous CRF receptors or neuronal activity blocked the effects of acute stress on Abeta. Thus, behavioral stressors can rapidly increase ISF Abeta through neuronal activity in a CRF-dependent manner, and the results suggest a mechanism by which behavioral stress may affect Alzheimer's disease pathogenesis.
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“Extracellular occurrence of oligomers is consistent with the rapid outpouring of Aβ, and perhaps small oligomers, into brain interstitial fluid, measured by microdialysis in mouse models and humans (Cirrito et al., 2005; Kang et al., 2007; Kang et al., 2009).”
From The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease (2011) · cites this paper as Kang et al., 2007
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Metadata
- Authors
- Kang, J.-E., Cirrito, J. R., Dong, H., Csernansky, J. G., & Holtzman, D. M.
- Affiliations
- Washington University in St. Louis (US)
- Departments of *Neurology,
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2007-06-19
- Volume
- 104
- Issue
- 25
- Pages
- 10673-10678
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1965571
- OpenAlex
- W2031441539
- Cited by
- 219
- References
- 44
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 10 · 2023: 11 · 2022: 7 · 2021: 12 · 2020: 9 · 2019: 12 · 2018: 13 · 2017: 11 · 2016: 5 · 2015: 17 · 2014: 12 · 2013: 14 · 2012: 10
- FWCI
- 10.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Alzheimer's Association (AG13956)
- Eli Lilly and Company
- Cure Alzheimer's Fund
- National Institutes of Health (AG13956)
- National Institute on Aging (AG 025824, R01AG013956, R01AG025824, R37AG013956, AG13956)
- National Institute on Drug Abuse (DA07261, T32DA007261)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- amyloid-beta, interstitial fluid, acute stress, restraint stress, isolation stress, corticotropin-releasing factor, CRF receptors, neuronal activity, synaptic activity, amyloid precursor protein transgenic mice, Alzheimer's disease, corticosterone
- MeSH terms
- Acute Disease, Animals, Corticotropin-Releasing Hormone, Crosses, Genetic, Female, Male, Mice, Inbred C57BL, Mice, Transgenic, Neurons, Stress, Psychological, Amyloid beta-Peptides, Microdialysis, Extracellular Fluid, Mice
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