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. 2008 Feb 6;431(3):197-200.
doi: 10.1016/j.neulet.2007.11.032. Epub 2007 Dec 3.

The effect of stress on the expression of the amyloid precursor protein in rat brain

Rachel Sayer  1 , Deborah Robertson, David J K Balfour, Kieran C Breen, Caroline A Stewart
Affiliations

The effect of stress on the expression of the amyloid precursor protein in rat brain

Rachel Sayer et al. Neurosci Lett. .

Abstract

The abnormal processing of the amyloid precursor protein (APP) is a pivotal event in the development of the unique pathology that defines Alzheimer's disease (AD). Stress, and the associated increase in corticosteroids, appear to accelerate brain ageing and may increase vulnerability to Alzheimer's disease via altered APP processing. In this study, rats were repeatedly exposed to an unavoidable stressor, an open elevated platform. Previous studies in this laboratory have shown that a single exposure produces a marked increase in plasma corticosterone levels but animals develop tolerance to this effect between 10 and 20 daily sessions. Twenty-four hours after stress, there was an increase in the ratio of the deglycosylated form of APP in the particulate fraction of the brain, which subsequently habituated after 20 days. The levels of soluble APP (APPs) tended to be lower in the stress groups compared to controls except for a significant increase in the hippocampus after 20 days of platform exposure. Since APPs is reported to have neurotrophic properties, this increased release may represent a neuroprotective response to repeated stress. It is possible that the ability to mount this response decreases with age thus increasing the vulnerability to stress-induced AD-related pathology.

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Figures

Fig. 1
Fig. 1
APP protein expression in soluble brain fractions. Striatum (STR), hippocampus (HPC), frontal cortex (FCX) and parietal cortex (PCX) generated from control rats and rats exposed to the elevated platform for 1 day (acute), 10 and 20 days. Values represent mean ± S.E.M. (n = 5 in each group). Representative blots are shown with the molecular weight of the protein bands indicated.
Fig. 2
Fig. 2
APP protein expression in particulate brain fractions. Striatum (STR), hippocampus (HPC), frontal cortex (FCX) and parietal cortex (PCX) generated from control rats and rats stressed on an elevated platform for 1 day (acute), 10 and 20 days. (A) Total APP protein expression in the particulate brain fractions. (B) The lower molecular weight band of the particulate form of APP (121 kDa) expressed as a percentage of total particulate APP levels. Representative blots are shown with the molecular weights of the protein bands indicated.
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