Chronic corticosterone-induced depression mediates premature aging in rats.

Background: Stress hormones such as corticosterone (CORT) play an essential role in the development of depression. Chronic CORT administration has been shown to induce dysfunction in the hypothalamic-pituitary-adrenal axis leading to depression, which was in turn associated with accelerated aging. However, the effect of CORT administration on aging remains unclear.

Methods: Rats were acclimatized for 1 week and then injected daily with CORT (40mg/kg) or vehicle (n = 10 each) for 21 consecutive days. Age-related indexes were then compared between CORT-treated rats and control rats.

Results: CORT induced affective behaviors indicative of depressive-like symptoms in rats, including reduced sucrose preference and increased immobility time in the forced swimming test. CORT-treated rats exhibited telomere shortening, possibly contributing to decreased telomerase activity and down-regulated expression of telomere-binding factor 2, correlated with enhanced oxidative damage. This was associated with inhibition of sirtuin 3 leading to reduced activities of superoxide dismutase 2 and glutathione reductase. CORT-treated rats showed degenerated mitochondrial functions represented by decreased adenosine triphosphate production, decreased nicotinamide adenine dinucleotide content, and decreased activity of nicotinamide phosphoribosyltransferase.

Limitations: The group sample sizes were small, and only male rats and a single dose level of CORT were used.

Conclusion: These findings demonstrate that CORT-induced depression may be involved in mediating the pathophysiology of premature aging in rats.