S-Space College of Medicine/School of Medicine (의과대학/대학원) Pharmacology (약리학전공) Journal Papers (저널논문_약리학전공)
Chronic stress accelerates learning and memory impairments and increases amyloid deposition in APPV717I-CT100 transgenic mice, an Alzheimer's disease model
- Jeong, Yun Ha; Park, Cheol Hyoung; Yoo, Jongman; Shin, Ki Young; Ahn, Sung-Min; Kim, Hye-Sun; Lee, Sang Hyung; Emson, Piers C.; Suh, Yoo-Hun
- Issue Date
- FASEB J. 2006 Apr;20(6):729-31. Epub 2006 Feb 8.
- Alzheimer Disease/genetics/*metabolism; Amyloid beta-Protein Precursor/genetics/*metabolism; Animals; Cerebral Cortex/metabolism; Chronic Disease; Corticosterone/blood; Disease Models, Animal; Hippocampus/metabolism; Learning Disorders/*metabolism; Memory Disorders/*metabolism; Mice; Mice, Transgenic; Restraint, Physical/adverse effects; Stress, Psychological/genetics/*metabolism
- Although chronic stress is known to be linked with memory and other neurological disorders, little is known about the relationship between chronic stress and the onset or development of Alzheimer's disease (AD). In this study, we investigated the effects of long-term stress on the onset and severity of cognitive deficits and pathological changes in APPV717I-CT100 mice overexpressing human APP-CT100 containing the London mutation (V717I) after exposure to immobilization stress. We found that chronic immobilization stress accelerated cognitive impairments, as accessed by the Passive avoidance and the Social Transfer of Food Preference (STFP) tests. Moreover, the numbers and densities of vascular and extracellular deposits containing amyloid beta peptide (Abeta) and carboxyl-terminal fragments of amyloid precursor protein (APP-CTFs), which are pathologic markers of AD, were significantly elevated in stressed animals, especially in the hippocampus. Moreover, stressed animals, also showed highly elevated levels of neurodegeneration and tau phosphorylation and increased intraneuronal Abeta and APP-CTFs immunoreactivities in the hippocampus and in the entorhinal and piriform cortex. This study provides the first evidence that chronic stress accelerates the onset and severity of cognitive deficits and that these are highly correlated with pathological changes, which thus indicates that chronic stress may be an important contributor to the onset and development of AD.
- 1530-6860 (Electronic)
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