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

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Abstract

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 β-amyloid (Aβ) peptides 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 Aβ 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 Aβ1-40/Aβ1-42. The effect of chronic stress on the severity of Aβ-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 Aβ, more so than that caused by Aβ alone. Additionally, there was a significantly greater impairment of early-phase long-term potentiation (E-LTP) in chronically stressed/Aβ-treated rats than in either the stressed or Aβ-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 Aβ-induced deficits of short-term memory and E-LTP by a mechanism involving decreased CaMKII activation along with increased calcineurin levels. © 2009 Society of Biological Psychiatry.

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Srivareerat, M., Tran, T. T., Alzoubi, K. H., & Alkadhi, K. A. (2009). Chronic Psychosocial Stress Exacerbates Impairment of Cognition and Long-Term Potentiation in β-Amyloid Rat Model of Alzheimer’s Disease. Biological Psychiatry, 65(11), 918–926. https://doi.org/10.1016/j.biopsych.2008.08.021

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