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

Abstract

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.

Influence of estrous cycle hormonal fluctuations and gonadal hormones on the ventilatory response to hypoxia in female rats

“…However, OVX animals had lower a ventilatory response to hypoxia than cycling rats in estrous. Fournier et al [17] showed that rats with reduced circulating levels of ovarian hormones (whether by ovariectomy or aging) had reduced hypoxic ventilatory responses when compared to young intact females. This result is in agreement with the findings of the present study, suggesting that ovarian hormones play a role in the ventilatory control system, providing an important signal that drives breathing.…”

Neonatal maternal separation opposes the facilitatory effect of castration on the respiratory response to hypercapnia of the adult male rat: Evidence for the involvement of the medial amygdala

“…Nonseparated control animals (CTRL) were continuously maintained under standard animal care procedures throughout the neonatal period with minimal human intervention. Because short periods of handling has distinct effects on HPA development, these animals are the most desirable control group for investigations of the effects of NMS on central nervous system development . On postnatal day 21, rats were weaned and housed two per cage under standard animal care conditions until adulthood (8‐10 weeks old), at which time the ventilatory measurements were performed.…”

“…Ventilation was measured in unrestrained and awake rats using a whole‐body, flow‐through plethysmograph (PLY3223; Buxco Electronics, Sharon, CT, USA) as reported previously . Briefly, the system consists of a 2‐L Plexiglas experimental chamber.…”

Neonatal Maternal Separation Augments Carotid Body Response to Hypoxia in Adult Males but Not Female Rats

“…Two days after delivery, litters were culled to 12 pups, when necessary, with a roughly equal number of males and females. The NMS protocol was identical to the one used in previous studies (Genest et al, 2004 ; Fournier et al, 2015 ). Briefly, the entire litter was separated from their mother for 3 h/day (09.00–12.00 h) from post-natal days 3 to 12.…”