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Effects of Pup Separation on Stress Response in Postpartum Female Rats.

ABSTRACT: There is a complex collection of neuroendocrine function during the postpartum period. Prolactin (PRL) released by suckling stimulus and its PRL receptors (PRL-R) in the central nervous system (CNS) are involved in hyporesponsiveness of the hypothalamic-pituitary-adrenal (HPA) axis in lactating mammals including rodents and humans. It is not clear how long it takes to reestablish the attenuated HPA axis activity of lactating rats to a pre-pregnancy state after pup separation. We first tested the hypothesis that HPA axis activity in response to an acute stress in postpartum rats would return to a pre-pregnancy state after pup separation. Restraint stress for 30 min was performed at the end of pup separation as an acute stressor. Plasma levels of corticosterone (CORT) were measured following restraint stress or no-stress (control) in virgin rats and postpartum rats housed with their pups or with pup removal for different periods of time of one hour, 24 h, or eight days. We then tested the hypothesis that circulating PRL level and CNS PRL-R gene expression were involved in mediating the acute stress response in postpartum rats. Plasma levels of PRL and PRL-R mRNA levels in the choroid plexus of the CNS were determined in both no-stress and stress, virgin rats, and postpartum rats housed with their pups or with pup removal for various periods, and their correlation with plasma CORT levels was assessed. The results demonstrated that PRL levels declined to virgin state in all postpartum rats separated from their pups, including the dams with one-hour pup separation. Stress-induced HPA activity dampened in lactating rats housed with pups, and returned to the pre-pregnancy state after 24 h of pup separation when both circulating PRL level and CNS PRL-R expression were restored to a pre-pregnancy state. Additionally, basal plasma CORT and CNS PRL-R expression were significantly correlated in rats with various pup status. This study suggested that stress-induced HPA activation occurred when PRL-R expression was similar to the level of virgin females, indicating that PRL-R upregulation contributes to an attenuated HPA response to acute stress. Understanding neuroendocrine responses to stress during the postpartum period is critical to understand postpartum-related neuropsychiatric illnesses and to maintain mental health in postpartum women.

SUBMITTER: Kalyani M

PROVIDER: S-EPMC5535863 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Effects of Pup Separation on Stress Response in Postpartum Female Rats.

Kalyani Manu M Callahan Phyllis P Janik James M JM Shi Haifei H

International journal of molecular sciences 20170627 7

There is a complex collection of neuroendocrine function during the postpartum period. Prolactin (PRL) released by suckling stimulus and its PRL receptors (PRL-R) in the central nervous system (CNS) are involved in hyporesponsiveness of the hypothalamic-pituitary-adrenal (HPA) axis in lactating mammals including rodents and humans. It is not clear how long it takes to reestablish the attenuated HPA axis activity of lactating rats to a pre-pregnancy state after pup separation. We first tested the ...[more]

PMID: 28654010

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Project description:Acute swim stress results in the robust production of several neuroactive steroids, which act as mediators of the stress response. These steroids include glucocorticoids, and positive GABAA receptor modulatory steroids such as allopregnanolone and tetrahydrocorticosterone (THDOC), which potentiate inhibitory GABA signalling, thereby playing a role in the negative control of the hypothalamic-pituitary-adrenal (HPA) axis. Prenatally stressed (PNS) offspring exhibit increased vulnerability to stress-related disorders and frequently display exaggerated HPA axis responses to stressors during adulthood, which may be a result of reduced neuroactive steroid production and consequently inhibitory signalling. Here, we investigated whether exposure of rats to prenatal social stress from gestational day 16-20 altered neuroactive steroid production under non-stress conditions and in response to an acute stressor (swim stress) in adulthood. Using liquid chromatography-mass spectrometry, nine neuroactive steroids were quantified (corticosterone, deoxycorticosterone [DOC], dihydrodeoxycorticosterone, THDOC, progesterone, dihydroprogesterone, allopregnanolone, pregnenolone, testosterone) in plasma and in five brain regions (frontal cortex, hypothalamus, amygdala, hippocampus, brainstem) of male and female control and PNS rats. There was no difference in the neuroactive steroid profile between control and PNS rats under basal conditions. The increase in circulating corticosterone induced by acute swim stress was similar in control and PNS offspring. However, greater stress-induced corticosterone and DOC concentrations were observed in the brainstem of male PNS offspring, whereas DOC concentrations were lower in the hippocampus of PNS females compared to controls, following acute stress. Although PNS rats did not show deficits in allopregnanolone responses to acute stress, there were modest deficits in the production of THDOC in the brainstem, amygdala, and frontal cortex of PNS males and in the frontal cortex of PNS females. The data suggest that neuroactive steroid modulation of GABAergic signalling following stress exposure may be affected in a sex- and region-specific manner in PNS offspring.

Project description:BackgroundPost-traumatic stress disorder (PTSD) affects men and women differently. Not only are women twice as likely as men to develop PTSD, they experience different symptoms and comorbidities associated with PTSD. Yet the dearth of preclinical research on females leaves a notable gap in understanding the underlying neuropathology of this sex difference.MethodsUsing two standard measures of PTSD-like responses in rats, the acoustic startle response (ASR) and dexamethasone suppression test (DST), we tested the effects of traumatic stress in adult male and female rats using two rodent models of PTSD, single prolonged stress and predator exposure. We then examined the neural correlates underlying these responses with cFos and glucocorticoid receptor immunohistochemistry in brain regions implicated in the traumatic stress response.ResultsWe now report that adult male and female rats across two models of PTSD show consistent sex-specific responses that recapitulate fundamental differences of PTSD in men and women. Trauma-exposed males showed the well-established hyper-responsive phenotype of enhanced ASR and exaggerated negative feedback control of the hypothalamic-pituitary-adrenal axis, while the same traumatic event had little effect on these same measures in females. Dramatic sex differences in how trauma affected cFos and glucocorticoid receptor expression in the brain lend further support to the idea that the trauma response of male and female rats is fundamentally different.ConclusionsTwo standard measures, ASR and DST, might suggest that females are resilient to the effects of traumatic stress, but other measures make it clear that females are not resilient, but simply respond differently to trauma. The next important question to answer is why. We conclude that males and females show fundamentally different responses to trauma that do not simply reflect differences in resilience. The divergent effects of trauma in the brains of males and females begin to shed light on the neurobiological underpinnings of these sex differences, paving the way for improved diagnostics and therapeutics that effectively treat both men and women.

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Dataset Information

Effects of Pup Separation on Stress Response in Postpartum Female Rats.

Publications

Effects of Pup Separation on Stress Response in Postpartum Female Rats.

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