Chronic unpredictable stress and long-term ovariectomy affect arginine-vasopressin expression in the paraventricular nucleus of adult female mice

Arginine-Vasopressin (AVP) may regulate the hypothalamic-pituitary-adrenal axis (HPA) and its effects on depressive responses. In a recent study, we demonstrated that Chronic Unpredictable Stress (CUS) depressive effects are enhanced by long-term ovariectomy (a model of post-menopause). In the present study, we investigated the effects of long-term ovariectomy and CUS on AVP expression in different subdivision of the paraventricular nucleus (PVN) of female mice. Both long-term ovariectomy and CUS affect AVP immunoreactivity in some of the PVN subnuclei of adult female mice. In particular, significant changes on AVP immunoreactivity were observed in magnocellular subdivisions, the paraventricular lateral magnocellular (PaLM) and the paraventricular medial magnocellular (PaMM), the 2 subnuclei projecting to the neurohypophysis for the hormonal regulation of body homeostasis. AVP immunoreactivity was decreased in the PaLM by both the long-term deprivation of ovarian hormones and the CUS. In contrast, AVP immunoreactivity was increased in the PaMM by CUS, whereas it was decreased by ovariectomy. Therefore, present results suggest morphological and functional differences among the PVN's subnuclei and complex interactions among CUS, gonadal hormones and AVP immunoreactivity.Depto. de Medicina Legal, Psiquiatría y PatologíaFac. de MedicinaTRUEpu

Prenatal stress induces long-term effects in cell turnover in the hippocampus-hypothalamus-pituitary axis in adult male rats

Subchronic gestational stress leads to permanent modifications in the hippocampus-hypothalamus-pituitary-adrenal axis of offspring probably due to the increase in circulating glucocorticoids known to affect prenatal programming. The aim of this study was to investigate whether cell turnover is affected in the hippocampus-hypothalamus-pituitary axis by subchronic prenatal stress and the intracellular mechanisms involved. Restraint stress was performed in pregnant rats during the last week of gestation (45 minutes; 3 times/day). Only male offspring were used for this study and were sacrificed at 6 months of age. In prenatally stressed adults a decrease in markers of cell death and proliferation was observed in the hippocampus, hypothalamus and pituitary. This was associated with an increase in insulin-like growth factor-I mRNA levels, phosphorylation of CREB and calpastatin levels and inhibition of calpain -2 and caspase -8 activation. Levels of the anti-apoptotic protein Bcl-2 were increased and levels of the pro-apoptotic factor p53 were reduced. In conclusion, prenatal restraint stress induces a long-term decrease in cell turnover in the hippocampus-hypothalamus-pituitary axis that might be at least partly mediated by an autocrine-paracrine IGF-I effect. These changes could condition the response of this axis to future physiological and pathophysiological situations. © 2011 Baquedano et al.Peer Reviewe

The weight gain response to stress during adulthood is conditioned by both sex and prenatal stress exposure

Food intake and weight gain are known to be affected by stress. However, the type and duration of the stress may have variable effects, with males and females responding differently. We report the short-term and long-term effects of prenatal and adult immobilization stress, as well as the combination of these two stresses, on weight gain and food intake in male and female rats and the role of post-pubertal gonadal hormones in this process. No long-term effect of prenatal stress on food intake or weight gain was found in either sex. However, during the period of adult stress [at postnatal day (P) 90; 10 days duration] stressed male rats gained significantly less weight than controls and previous exposure to prenatal stress attenuated this effect (control: 31.2 ± 2.1 g; prenatal stress: 24.6 ± 3.8 g; adult stress: 8.1 ± 3.4 g; prenatal and adult stress: 18.2 ± 3.3 g; p< 0.0001). There was no change in food intake in response to either prenatal or adult stress. Adult stress increased circulating corticosterone levels during the initial part of the stress period, in both male and female rats with this rise being greater in male rats. No effect on corticosterone levels was observed on the last day of stress in either sex. No effect on weight gain or food intake was observed in female rats. Following adult stress, male rats increased their weight gain, with no change in food intake, such that 1 month later they reached control levels. At the time of sacrifice (P180), there were no differences in weight or circulating metabolic hormone levels between any of the male groups. Although castration alone modulated body weight in both male and female rats, it did not affect their weight gain response to adult stress. These results indicate that the weight gain response to adult stress is sexually dimorphic and that this is not dependent on post-pubertal gonadal steroids. Furthermore, the outcome of this response closely depends on the time at which the change in weight is analyzed, which could help to explain different results reported in the literature. Indeed, weight and metabolic hormone levels were normalized by the end of the study. © 2009 Elsevier Ltd.Peer Reviewe