Effects chronic administration of corticosterone and estrogen on HPA axis activity and telomere length in brain areas of female rats.

Chronic stress is related to the acceleration of telomere shortening. Recent work showed a correlation between chronic psychosocial stress and reduced telomere length in certain cells. The exposure of T lymphocytes to cortisol promoted a significant reduction in telomerase activity. Although stress can promote changes in telomere length, whether increased glucocorticoid concentrations alter telomere length in brain tissue cells is unclear. In addition to modulating the activity of the stress system, estrogen also influences telomere length. The objective of this study was to verify whether chronic exposure to glucocorticoids promotes changes in the telomere length of encephalic areas involved in the control of HPA axis activity and whether estrogen affects these changes. Wistar rats were ovariectomized and treated with estradiol cypionate [(50 or 100 µg/kg, subcutaneously)] or oil and 20 mg/kg corticosterone or vehicle (isotonic saline with 2% Tween 80, subcutaneously) for 28 days. On the day after the end of the hormonal treatment, the animals were euthanized for collection of blood, brain and pituitary gland samples. Estrogen modulated the activity of the HPA axis. CRH, AVP and POMC mRNA levels were reduced by estrogen. At least in doses and treatment time used, there was no correlation between effects of exposure to glucocorticoids and estrogen on telomere length in the brain areas of female rats. However, estrogen treatment reduced the telomere length in the central amygdala and dorsal hippocampus, but not in the PVN, indicating a variation of reaction of telomeres for estrogen in different brain areas.

Sex differences in body composition, metabolism-related hormones, and energy homeostasis during aging in Wistar rats.

Aging affects the body composition and balance of energy metabolism. Here, we collected in a single work several physiological parameters to show how aging and sex differences can influence energy homeostasis. Body mass index (BMI), Lee index, glucose tolerance, glycemia, and lipidogram in fasting were measured in male and female Wistar rats at the ages of 2, 6, 9, 12, and 18 months. We also measured the lipid profile, free fatty acids, glycerol, glycemia, leptin, adiponectin, insulin, corticosterone (CORT), prolactin (PRL), thyroid stimulated hormone, and triiodothyronine (T3) in 3- and 18-month-old rats of both sexes, fed ad libitum. Animals were classified as obese beginning at 2 months in males and 6 months in females. Aged male rats showed hyperglycemia and glucose intolerance compared to young males and old females. In the ad libitum condition, the 18-month males presented higher serum levels of triglycerides, total cholesterol, and free fatty acids than females. The 18-month-old females had higher PRL and CORT concentration than males, but insulin and T3 were higher in 18-month-old males than females. Our work demonstrated that aging processes on energy metabolism in rats is sex specific, with a better lipid profile and glucose tolerance in aged females.

Increases in plasma corticosterone and stretched-attend postures in rats naive and previously exposed to the elevated plus-maze are sensitive to the anxiolytic-like effects of midazolam.

A single exposure to the elevated plus-maze test (EPM) reduces or abolishes the anxiolytic efficacy of benzodiazepines on a second trial. This phenomenon known as one-trial tolerance (OTT) is considered to be due to a shift in the emotional state of the animals across the test/retest sessions. Activation of the hypothalamic-pituitary-adrenocortical (HPA) axis has been considered to be an adaptive response to stressful or challenging situations such as height and openness of the EPM. This work looks at the phenomenon of OTT to the benzodiazepine compound midazolam through the conjoint examination of the novel ethological measures of the EPM and adrenocortical response of rats exposed to single and repeated sessions of the EPM. The results obtained confirmed that the approach/avoidance conflict on the first trial of the EPM is very sensitive to the anxiolytic effects of benzodiazepines. Moreover, stressful stimuli present upon initial exposure to the EPM render the standard measures of the EPM resistant to the anxiolytic effects of benzodiazepines on retest. However, the increases in plasma corticosterone and in risk assessment behavior observed in rats submitted to single or repeated sessions in the EPM were reversed by pretreatment with midazolam. The administration of metyrapone, a glucocorticoid synthesis blocker, decreased risk assessment but did not affect locomotion and anxiety-like behaviors. It is suggested that the detection of the dangerous environment through the stretched-attend postures in the second trial leads to the known low level of exploration and the consequent OTT upon retest. Moreover, in view of the similarity between the risk assessment and plasma corticosterone patterns in both naive and experienced rats, this hormone-behavior profile may be crucial for the expression of OTT to benzodiazepines in rodents exposed to the EPM.