Sébastien Fournier

Chronic corticosterone elevation and sex‐specific augmentation of the hypoxic ventilatory response in awake rats

Perinatal stress disrupts normal development of the hypothalamo‐pituitary‐adrenal (HPA) axis. Adult male (but not female) rats previously subjected to a stress such as neonatal maternal separation (NMS) are characterized by chronic elevation of plasma corticosterone (Cort) levels and an abnormally elevated hypoxic ventilatory response through mechanisms that remain unknown. The present study tested the hypothesis that a chronic increase of plasma Cort levels alone augments the ventilatory response to hypoxia in adult rats. Three groups of Sprague–Dawley male and female rats were used (control, placebo and Cort implants). Rats subjected to chronic Cort elevation received a subcutaneous Cort implant (300 mg) 14 days prior to ventilatory measurements, whereas sham‐operated rats received placebo implants. Controls received no treatment. Plasma Cort levels and body weight profiles were measured to assess protocol efficiency. Whole body plethysmography was used to measure ventilatory activity and metabolic indices during normoxia and following a 20 min period of moderate hypoxia (12% O2). Male rats implanted with Cort showed a ventilatory response to hypoxia higher than placebo‐treated rats; this effect was mainly due to a larger tidal volume response. In females, Cort treatment increased the breathing frequency response but the effect on minute ventilation was not significant. Taken together, these data show that chronic elevation of Cort alone increases the ventilatory response to hypoxia, but in a sex‐specific manner. These data raise important questions regarding the mechanisms underlying the sexual dimorphism of this effect and the potential link between HPA axis dysfunction and respiratory disorders related to abnormal ventilatory chemoreflex.

Neonatal stress affects the aging trajectory of female rats on the endocrine, temperature and ventilatory responses to hypoxia

Human and animal studies on sleep-disordered breathing and respiratory regulation show that the effects of sex hormones are heterogeneous. Because neonatal stress results in sex-specific disruption of the respiratory control in adult rats, we postulate that it might affect respiratory control modulation induced by ovarian steroids in female rats. The hypoxic ventilatory response (HVR) of adult female rats exposed to neonatal maternal separation (NMS) is ∼30% smaller than controls (24), but consequences of NMS on respiratory control in aging female rats are unknown. To address this issue, whole body plethysmography was used to evaluate the impact of NMS on the HVR (12% O2, 20 min) of middle-aged (MA; ∼57 wk old) female rats. Pups subjected to NMS were placed in an incubator 3 h/day for 10 consecutive days (P3 to P12). Controls were undisturbed. To determine whether the effects were related to sexual hormone decline or aging per se, experiments were repeated on bilaterally ovariectomized (OVX) young (∼12 wk old) adult female rats. OVX and MA both reduced the HVR significantly in control rats but had little effect on the HVR of NMS females. OVX (but not aging) reduced the anapyrexic response in both control and NMS animals. These results show that hormonal decline decreases the HVR of control animals, while leaving that of NMS female animals unaffected. This suggests that neonatal stress alters the interaction between sex hormone regulation and the development of body temperature, hormonal, and ventilatory responses to hypoxia.

Testosterone potentiates the hypoxic ventilatory response of adult male rats subjected to neonatal stress

What is the central question of this study? Does testosterone contribute to the enhancement of the hypoxic ventilatory response observed in stressed rats? What is the main finding and its importance? Castration reduces the hypoxic ventilatory response of stressed rats (but not control rats). Neonatal stress disrupts the gonadotrophic axis and its impact on respiratory control. These results bring new insight into the pathophysiology of sleep‐disordered breathing and the sex‐based difference in its prevalence.