Effects of maternal and sibling deprivation on basal and stress induced hypothalamic-pituitary-adrenal components in the infant rat

Abstract

Prolonged maternal deprivation during early infancy increases basal-and stress-induced corticosterone (CORT) levels, but the underlying mechanism is not clear. In general, stressors activate the hypothalamic-pituitary-adrenal (HPA) axis, with secretion and compensatory synthesis of hypothalamic corticotropin-releasing hormone (CRH). In the infant rat, we have demonstrated that maximally tolerated acute cold stress induced a robust elevation of plasma CORT throughout the first 2 postnatal weeks. However CRH messenger RNA (CRH-mRNA) abundance 4 h subsequent to cold stress was enhanced only in rats aged 9 days or older. This suggests a developmental regulation of the CRH component of the HPA-response to this stressor. The present study examined whether increased basal and cold stress-induced CORT levels after 24 h of maternal deprivation were due to enhanced CRH-mRNA abundance in the hypothalamic paraventricular nucleus (PVN). CRH-mRNA abundance, and basal-and cold-induced plasma CORT levels were measured in maternally deprived 6 and 9-day-old pups compared to nondeprived controls. Maternal deprivation increased basal and cold-induced CORT levels on both 6 and 9-day-old rats. CRH-mRNA abundance in the PVN of deprived rats did not differ from that in non-deprived rats. Our results indicate that the enhanced basal and stress-induced plasma CORT observed after 24 h maternal deprivation is not due to increased CRH-mRNA abundance in the PVN. KeywordsMaternal deprivation; Stress; Infant rat; Development; Corticosterone; Corticotropin releasing hormone; Messenger RNA; Hypothalamic-pituitary-adrenal Mechanisms of the activation of the hormonal stress response in the immature rat are not fully understood [7,10,14,18]. In the mature animal, a variety of stressors induce secretion of corticotropin-releasing hormone (CRH) from the hypothalamic paraventricular nucleus (PVN) causing ACTH release from the pituitary and increasing plasma glucocorticoids (GCs). This is followed by a 'compensatory' increase in CRH-mRNA abundance in the hypothalamic PVN [7,10,21]. We have established that CRH-mRNA abundance in the PVN does not increase subsequent to maximal tolerated acute-cold stress in rats aged 4 or 6 days, The infant hypothalamic-pituitary-adrenal (HPA) axis is under maternal regulation [6,9,13,16,17]. Prolonged, 24 h maternal deprivation has been found to increase basal plasma corticosterone (CORT) levels and to enhance HPA axis responsiveness to further stressors [6,9,16]. Shorter periods of maternal deprivation (1, 2, 4, and 8 h) have been shown to have only a minimal effect on basal CORT levels and the response to acute stress [9,16]. The mechanisms underlying increased basal and cold-induced plasma CORT subsequent to maternal deprivation have not been elucidated. The purpose of this study was to examine whether the enhanced basal HPA tone and the altered response of plasma CORT to acute stress observed after 24 h maternal deprivation were due to increased hypothalamic CRHmRNA abundance.Time pregnant Sprague-Dawley ra...

Neuronal activity and stress differentially regulate hippocampal and hypothalamic corticotropin-releasing hormone expression in the immature rat

“…Indeed, the presence of differential thresholds for the effects of a given stimulus on CRH function has recently been demonstrated. 55 However, the cold challenge employed here 60 is a powerful activator of the neuroendocrine stress response, resulting in markedly elevated plasma corticosterone 3,23,60 (Table 3). Therefore, the absence of an effect of cold challenge on hippocampal CRH expression, combined with the rapid and prolonged up-regulation of CRH mRNA levels in the hippocampus by hyperthermia, indicates that enhanced CRH gene transcription in the hippocampus requires factors other than provocation of physiological, hormonal responses to stress.…”

“…3,23,60 In brief, immature rats (n = 6 for ISH analysis, n = 4 for ICC) were separated from the mother and subjected to maximally tolerated cold exposure, defined by development of rigor and diminished response to tactile stimulus. Maximum exposure required 40-50 min at 4°C and resulted in an average rectal temperature of 11°C.…”

Differential regulation of glucocorticoid receptor messenger RNA (GR-mRNA) by maternal deprivation in immature rat hypothalamus and limbic regions

“…Pups were offspring of timed-pregnancy Sprague-Dawley dams [1][2][3]. Birth-date of pups was considered PND0; litters were culled to 12 and mixed among experimental groups.…”

“…Birth-date of pups was considered PND0; litters were culled to 12 and mixed among experimental groups. Cages were maintained as described [1][2][3][17][18][19], and procedures were approved by Institutional ACC. On the morning of PND8, rats were either placed individually in beakers, kept together separated from the dam, or left undisturbed in home cages with dams [1].…”

“…On the morning of PND9, undeprived pups were sacrificed within 3 min of disturbance [17], followed by MDep pups. Trunk blood was collected for ACTH and corticosterone analysis using radioimmunoassay (INCSTAR, Stillwater, MN and ICN Irvine, CA, respectively) [1][2][3]17]. Because plasma corticosterone levels of individually-and group-MDep rats did not differ, these groups were combined.…”