Chronic Psychosocial Stress Exacerbates Impairment of Cognition and Long-Term Potentiation in β-Amyloid Rat Model of Alzheimer's Disease

Background: Alzheimer's disease (AD) is a degenerative disorder that leads to progressive cognitive decline. Alzheimer's disease develops as a result of over-production and aggregation of beta-amyloid (A beta) pepticles in the brain. The reason for variation in the gravity of symptoms among AD patients is unknown and might result from patient-related factors including lifestyle. Individuals suffering from chronic stress are at an increased risk for developing AD. This study investigated the effect of chronic psychosocial stress in A beta rat model of AD. Methods: Psychosocial stress was induced with a rat intruder model. The rat model of AD was induced by 14-day osmotic pump infusion of a mixture of 300 pmol/day A beta(1-40)/A beta(1-42). The effect of chronic stress on the severity of A beta-induced spatial learning and memory impairment was tested by three approaches: behavioral testing in the radial arm water maze, in vivo electrophysiological recording in anesthetized rat, and immunoblot analysis to determine protein levels of learning- and memory-related molecules. Results: A marked impairment of learning and memory developed when stress was combined with A beta, more so than that caused by A beta alone. Additionally, there was a significantly greater impairment of early-phase long-term potentiation (E-LTP) in chronically stressed/A beta-treated rats than in either the stressed or A beta-treated rats. This might be a manifestation of the reduction in protein levels of calcium/calmodulin-dependent protein kinase II (CaMKII) and the abnormal increase in calcineurin levels. Conclusions: Chronic stress significantly intensified A beta-induced deficits of short-term memory and E-LTIP by a mechanism involving decreased CaMKII activation along with increased calcineurin levels.