Chronic stress accelerates learning and memory impairments and increases amyloid deposition in APPV717I-CT100 transgenic mice, an Alzheimer's disease model.
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.
Department of Pharmacology, College of Medicine, National Creative Research Initiative Centre for Alzheimer's Dementia and Neuroscience Research Institute, MRC, Seoul National University, Seoul, Korea.
Yun Ha
YH
Jeong
Cheol Hyoung
CH
Park
Jongman
J
Yoo
Ki Young
KY
Shin
Sung-Min
SM
Ahn
Hye-Sun
HS
Kim
Sang Hyung
SH
Lee
Piers C
PC
Emson
Yoo-Hun
YH
Suh
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D002908:Chronic Disease; D003345:Corticosterone / Q000097:blood; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism; D007859:Learning Disabilities / Q000378:metabolism*; D008569:Memory Disorders / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D012149:Restraint, Physical / Q000009:adverse effects; D013315:Stress, Psychological / Q000235:genetics / Q000378:metabolism*
D016564:Amyloid beta-Protein Precursor; D003345:Corticosterone