Chronic stress alters the expression levels of longevity-related genes in the rat hippocampus

• Chronic stress decreases the expression levels of sirtuin-1.
• Chronic stress increases the expression levels of p53 in the hippocampus.
• Chronic stress increases ROS production through NADPH oxidase and TXNIP induction.
• These effects are abolished by blocking the glucocorticoid receptor.
• Chronic stress could accelerate hippocampal aging.

The molecular mechanisms underlying the negative effects of psychological stress on cellular stress during aging and neurodegenerative diseases are poorly understood. The main objective of this study was to test the effect of chronic psychological stress, and the consequent increase of circulating glucocorticoids, on several hippocampal genes involved in longevity. Sirtuin-1, p53, thioredoxin-interacting protein, and heat shock protein 70 were studied at the mRNA and protein levels in stressed and non-stressed animals. Stress treatment for 10 days decreased sirtuin-1 and heat shock protein 70 levels, but increased levels of p53, thioredoxin-interacting protein and the NADPH oxidase enzyme. Examination of protein expression following two months of stress treatment indicated that sirtuin-1 remained depressed. In contrast, an increase was observed for thioredoxin-interacting protein, heat shock protein 70, p53 and the NADPH oxidase enzyme. The effect of stress was reversed by mifepristone, a glucocorticoid receptor antagonist. These data suggest that chronic stress could contribute to aging in the hippocampus.

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