The influence of early-life and adulthood stressors on brain neuropeptide-S system

Central administered neuropeptide-S (NPS) was shown to reduce stress response in rodents. This study aimed to investigate the alterations in NPS system upon chronic exposure to early-life and adulthood stressors. Newborn pups underwent maternal separation (MS) from postnatal day 1 to 14 comprised of daily 3-h separations. In the adulthood, 90-min of restraint stress was loaded to males as an acute stress (AS) model. For chronic homotypic stress (CHS), same stressor was applied for 5 consecutive days. The changes in the expression and the release of NPS were monitored by immunohistochemistry and microdialysis, respectively. Throughout the CHS, heart rate variability (HRV) was analyzed on a daily basis. The immunoreactivity for NPS receptor (NPSR) was detected in basolateral amygdala (BLA) and hypothalamic paraventricular nucleus (PVN) by immunofluorescence staining. The NPS expression in the brainstem was increased upon AS which was more prominent following CHS, whereas these responses were found to be blunted in MS counterparts. Similar to histological data, the stress-induced release of NPS in BLA was attenuated in MS rats. CHS-induced elevations in sympatho-vagal balance were alleviated in control rats; which was not observed in MS rats. The expression of NPSR in BLA and PVN was down-regulated in MS rats. The brain NPS/NPSR system appears to be susceptible to the early-life stressors and the subsequent chronic stress exposure in adulthood which results in altered autonomic outflow.