title: Chronic psychosocial stress enhances long-term depression in a subthreshold amyloid-beta rat model of Alzheimer's disease.
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.
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, Texas, USA.
authors.forename: Trinh T
authors.initials: TT
authors.lastname: Tran
authors.forename: Marisa
authors.initials: M
authors.lastname: Srivareerat
authors.forename: Ibrahim A
authors.initials: IA
authors.lastname: Alhaider
authors.forename: Karim A
authors.initials: KA
authors.lastname: Alkadhi
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced / Q000473:pathology / Q000523:psychology*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D056547:CA1 Region, Hippocampal / Q000378:metabolism; D019703:Calcineurin / Q000097:blood; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002908:Chronic Disease; D003863:Depression / Q000235:genetics / Q000503:physiopathology / Q000523:psychology*; D055724:Electrophysiological Phenomena; D006624:Hippocampus / Q000473:pathology; D015918:Infusion Pumps, Implantable; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012306:Risk; D012931:Social Environment; D013315:Stress, Psychological / Q000235:genetics / Q000503:physiopathology / Q000523:psychology*; D009435:Synaptic Transmission
chemical_list: D016229:Amyloid beta-Peptides; D019208:Brain-Derived Neurotrophic Factor; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D019703:Calcineurin; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509281:Bace1 protein, rat