Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 104, Issue 25, Pages 10673-10678Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0700148104
Keywords
Alzheimer's disease; synaptic activity; environmental stress; microdialysis; transgenic
Categories
Funding
- NIA NIH HHS [AG025824, AG13956, R37 AG013956, R01 AG013956, R01 AG025824] Funding Source: Medline
- NIDA NIH HHS [T32 DA007261, DA 07261] Funding Source: Medline
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Aggregation of the amyloid-beta (A beta) peptide in the extracellular space of the brain is critical in the pathogenesis of Alzheimer's disease. A beta 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 A beta levels, we assessed the effects of chronic and acute stress paradigms in amyloid precursor protein transgenic mice. Isolation stress over 3 months increased A beta levels by 84%. Similarly, acute restraint stress increased A beta 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 A beta. Thus, behavioral stressors can rapidly increase ISF A beta 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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