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Chronic psychosocial stress enhances long-term depression in a subthreshold amyloid-beta rat model of Alzheimer's disease.
- Source :
-
Journal of neurochemistry [J Neurochem] 2011 Oct; Vol. 119 (2), pp. 408-16. Date of Electronic Publication: 2011 Sep 20. - Publication Year :
- 2011
-
Abstract
- In addition to genetic aspects, environmental factors such as stress may also play a critical role in the etiology of the late onset, sporadic Alzheimer's disease (AD). The present study examined the effect of chronic psychosocial stress in a sub-threshold Aβ (subAβ) rat model of AD on long-term depression by two techniques: electrophysiological recordings of synaptic plasticity in anesthetized rats, and immunoblot analysis of memory- and AD-related signaling molecules. Chronic psychosocial stress was induced using a rat intruder model. The subAβ rat model of AD, which was intended to represent outwardly normal individuals with a pre-disposition to AD, was induced by continuous infusion of 160 pmol/day Aβ₁₋₄₂ via a 14-day i.c.v. osmotic pump. Results from electrophysiological recordings showed that long-term depression evoked in stress/subAβ animals was significantly enhanced compared with that in animals exposed to stress or subAβ infusion alone. Molecular analysis of various signaling molecules 1 h after induction of long-term depression revealed an increase in the levels of calcineurin and phosphorylated CaMKII in groups exposed to stress compared with other groups. The levels of the brain-derived neurotrophic factor (BDNF) were significantly decreased in stress/subAβ animals but not in stress or subAβ animals. In addition, the levels of beta-site amyloid precursor protein cleaving enzyme were markedly increased in stress/subAβ. These findings suggest that chronic stress may accelerate the impairment of synaptic plasticity and consequently cognition in individuals 'at-risk' for AD.<br /> (© 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.)
- Subjects :
- Alzheimer Disease chemically induced
Alzheimer Disease pathology
Amyloid Precursor Protein Secretases metabolism
Amyloid beta-Peptides administration & dosage
Animals
Aspartic Acid Endopeptidases metabolism
Blotting, Western
Brain-Derived Neurotrophic Factor metabolism
CA1 Region, Hippocampal metabolism
Calcineurin blood
Calcium-Calmodulin-Dependent Protein Kinase Type 2 metabolism
Chronic Disease
Depression genetics
Depression physiopathology
Electrophysiological Phenomena
Hippocampus pathology
Infusion Pumps, Implantable
Male
Peptide Fragments administration & dosage
Rats
Rats, Wistar
Risk
Stress, Psychological genetics
Stress, Psychological physiopathology
Synaptic Transmission
Alzheimer Disease psychology
Amyloid beta-Peptides pharmacology
Depression psychology
Peptide Fragments pharmacology
Social Environment
Stress, Psychological psychology
Subjects
Details
- Language :
- English
- ISSN :
- 1471-4159
- Volume :
- 119
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of neurochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 21854392
- Full Text :
- https://doi.org/10.1111/j.1471-4159.2011.07437.x