Chronic psychosocial stress triggers cognitive impairment in a novel at-risk model of Alzheimer's disease.
Although it is generally accepted that Abeta contributes to the pathogenesis of Alzheimer's disease (AD), other factors that impact the severity and time of onset of the disease are not well known. Aside from genetic factors, environmental factors such as stress may also play a critical role in the manifestation of AD. The present study examined the effect of chronic psychosocial stress in an at-risk, subthreshold Abeta (subAbeta) rat model of AD by three approaches: learning and memory tests in the radial arm water maze, electrophysiological recordings of long-term potentiation (LTP) in anesthetized rats, and immunoblot analysis of learning- and memory-related signaling molecules. Chronic psychosocial stress was induced using a rat intruder model. The subAbeta rat model of AD was induced by continuous i.c.v. infusion of 160 pmol/day Abeta(1-42) via a 14-day osmotic pump. Behavioral tests and electrophysiological recordings showed that subAbeta rats were not significantly different from control rats. However, chronically stressed subAbeta rats showed more significant impairment of cognitive functions and early-phase LTP (E-LTP) than that caused by stress alone. Molecular analysis of essential signaling molecules after induction of E-LTP revealed an increase in the levels of p-CaMKII in control as well as subAbeta infused rats, but not in stressed or stressed at-risk rats. In addition, compared to unstimulated control, the levels of both total CaMKII and calcineurin were increased in all stimulated animals groups after HFS. These findings suggest that the stress-induced alterations may accelerate the impairment of cognition and synaptic plasticity in individuals "at-risk" for AD.
Tran
Trinh T
TT
Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, USA.
Srivareerat
Marisa
M
Alkadhi
Karim A
KA
D000544:Alzheimer Disease / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D019703:Calcineurin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002908:Chronic Disease; D003072:Cognition Disorders / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D017774:Long-Term Potentiation / Q000502:physiology; D018782:Maze Learning / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D010446:Peptide Fragments / Q000378:metabolism / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D012919:Social Behavior; D013315:Stress, Psychological / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D019703:Calcineurin; D002118:Calcium