title: Chronic Stress Decreases Basal Levels of Memory-Related Signaling Molecules in Area CA1 of At-Risk (Subclinical) Model of Alzheimer's Disease.
abstract: An important factor that may affect the severity and time of onset of Alzheimer's disease (AD) is chronic stress. Epidemiological studies report that chronically stressed individuals are at an increased risk for developing AD. The purpose of this study was to reveal whether chronic psychosocial stress could hasten the appearance of AD symptoms including changes in basal levels of cognition-related signaling molecules in subjects who are at risk for the disease. We investigated the effect of chronic psychosocial stress on basal levels of memory-related signaling molecules in area CA1 of subclinical rat model of AD. The subclinical symptomless rat model of AD was induced by osmotic pump continuous intracerebroventricular (ICV) infusion of 160 pmol/day Aβ1-42 for 14 days. Rats were chronically stressed using the psychosocial stress intruder model. Western blot analysis of basal protein levels of important signaling molecules in hippocampal area CA1 showed no significant difference between the subclinical AD rat model and control rat. Following six weeks of psychosocial stress, molecular analysis showed that subclinical animals subjected to stress have significantly reduced basal levels of p-CaMKII and decreased p-CaMKII/t-CaMKII ratio as well as decreased basal levels of p-CREB, total CREB, and BDNF. The present results suggest that these changes in basal levels of signaling molecules may be responsible for impaired learning, memory, and LTP in this rat model, which support the proposition that chronic stress may accelerate the emergence of AD in susceptible individuals.
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, 77204, USA, kalkadhi@uh.edu.
authors.forename: Karim A
authors.initials: KA
authors.lastname: Alkadhi
authors.forename: Trinh T
authors.initials: TT
authors.lastname: Tran
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D056547:CA1 Region, Hippocampal / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D019703:Calcineurin / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002908:Chronic Disease; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004195:Disease Models, Animal; D008568:Memory; D010766:Phosphorylation; D017208:Rats, Wistar; D015398:Signal Transduction; D013315:Stress, Psychological / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D019703:Calcineurin
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