Placental corticotrophin-releasing hormone trajectories in pregnancy: Associations with postpartum depressive symptoms.

OBJECTIVE: Depressive symptoms following birth are common and can have adverse effects for mothers, children, and families. Changes in hypothalamic-pituitary-adrenal (HPA) axis regulation during pregnancy may be implicated in the development of postpartum depressive symptoms, particularly changes in placental corticotropinreleasing hormone (pCRH). However, few studies have tested how dynamic pCRH changes over pregnancy relate to postpartum depressive symptoms. This preregistered investigation tests associations of both pCRH levels and changes from early to late pregnancy with postpartum depressive symptoms. METHODS: The sample consists of 173 women studied in early, mid, and late pregnancy who later reported on depressive symptoms with the Edinburgh Postpartum Depression Scale during interviews at 1, 6 and 12 months postpartum. Blood samples were collected at each prenatal timepoint and assayed for pCRH using radioimmunoassay. Latent growth curve analysis was employed to identify distinct trajectories of pCRH during pregnancy. RESULTS: We identified three prenatal pCRH trajectories labeled as typical, flat, and accelerated. Each trajectory showed exponential increases in pCRH levels over the course of gestation but differed in overall levels and rates of change. pCRH levels were not associated with postpartum depressive symptoms. However, women with accelerated pCRH trajectories reported marginally higher depressive symptoms one month postpartum. Primary analysis models adjusted for marital status, income, prepregnancy BMI, parity, prenatal depressive symptoms, and gestational age. CONCLUSIONS: These findings add to our understanding of dynamic changes to maternal HPA axis regulation during pregnancy and contribute to growing evidence on how pCRH changes relate to the development of postpartum depressive symptoms.

Linking stress with urocortin in rats.

The corticotropin-releasing factor neuropeptides (CRH and UCN-1,2,3), as well as spexin, contribute to the control of energy balance and limit food intake in mammals. However, the role of these neuropeptides in chronic variable stress remains unknown. The effect of chronic varied stress on circulating corticosterone levels and urocortin expression levels in the brains of experimental rats was studied in this study. Rats were subjected with 28 days long term stress protocol, end of stress protocol experimental and control animal organs isolated, brain urocorcortin-1,2,3 expression by RT-PCR and serum corticosterone by ELISA method. UCN levels in the brain were altered in rats subjected to prolonged varied stress. Furthermore, corticosterone levels were elevated as a result of the same urocortin expression pattern, indicating that urocortin expression is controlled by glucocorticoids via a glucocorticoid-responsive element (GRE). Thus, data shows that hypothalamus-pituitary-adrenal (HPA) axis, also known as the LHPA axis, and limbic system are both stimulated by stress, which is reflected in the form of elevated corticosterone levels, according to the genes UCN1, 2, and 3.

Hypothalamic corticotrophin releasing hormone neurons in stress-induced psychopathology: Revaluation of synaptic contributions.

Stress has a strong influence on mental health around the world. Decades of research has sought to identify mechanisms through which stress contributes to psychiatric disorders such as depression, to potentially guide the development of therapeutics targeting stress systems. The hypothalamic pituitary adrenal (HPA) axis is the key endocrine system that is responsible for coordinating body-wide changes that are necessary for survival under stress, and much of the research aimed at understanding the mechanisms by which stress contributes to depression has focussed on HPA axis dysfunction. Corticotrophin releasing hormone (CRH) neurons in the paraventricular nucleus of the hypothalamus (PVN) sit at the apex of the HPA axis, integrating signals relevant to stress and external threats, to ensure HPA axis activity is appropriate for the given context. In addition to this, emerging research has demonstrated that neural activity in PVNCRH neurons regulates stress related behaviours via modulation of downstream synaptic targets. This review will summarize convergent evidence from preclinical studies on chronic stress and clinical research in mood disorders demonstrating changes in PVNCRH neural function, consider how this may influence synaptic targets of PVNCRH neurons, and discuss the potential role of these PVNCRH synaptic pathways in the development of maladaptive behaviours following chronic stress that are relevant to depression. We will also highlight important questions for future research aimed at precisely dissecting endocrine and synaptic roles of PVNCRH neurons in chronic stress, their potential interactions, and therapeutic opportunities for the treatment of stress related disorders.

Local CRF and oxytocin receptors correlate with female experience-driven avoidance change and hippocampal neuronal plasticity.

Understanding how experiences affect females' behaviors and neuronal plasticity is essential for uncovering the mechanism of neurodevelopmental disorders. The study explored how neonatal maternal deprivation (MD) and post-weaning environmental enrichment (EE) impacted the CA1 and DG's neuronal plasticity in the dorsal hippocampus, and its relationships with passive avoidance, local corticotrophin-releasing factor (CRF) levels, and oxytocin receptor (OTR) levels in female BALB/c mice. The results showed that MD damaged passive avoidance induced by foot shock and hotness, and EE restored it partially. In the CA1, MD raised CRF levels and OTR levels. Parallelly, MD increased synaptic connection levels but reduced the branches' numbers of pyramidal neurons. Meanwhile, in the DG, MD increased OTR levels but lowered CRF levels, DNA levels, and spine densities. EE did not change the CA1 and DG's CRF and OTR levels. However, EE added DG's dendrites of granular cells. The additive of MD and EE raised CA1's synaptophysin and DG's postsynaptic density protein-95 and OTR levels, and meanwhile, shaped avoidance behaviors primarily similar to the control. The results suggest that experience-driven avoidance change and hippocampal neuronal plasticity are associated with local CRF and OTR levels in female mice.

Serum oxytocin and corticotropin-releasing hormone levels in the third trimester of pregnancy for predicting postpartum depression in Thai women.

PURPOSE: This prospective observational study aimed to determine whether serum oxytocin (OT) or corticotrophin-releasing hormone (CRH) levels in the third trimester of pregnancy (or late pregnancy) could prospectively predict postpartum depression (PPD) at six weeks after childbirth. METHODS: We measured late pregnancy OT and CRH levels in Thai women, assessed depression using the Edinburgh Postnatal Depression Scale (EPDS) and Patient Health Questionnaire-9 (PHQ-9), and collected mothers, labor, and newborn data. At six weeks postpartum, an EPDS score ≥ 11 or PHQ-9 score ≥ 10 was defined as the presence of PPD. Multivariable binary logistic regression analysis was performed to determine the predictors of PPD. RESULTS: Of 200 participants, 136 (68.0%) were reassessed at six weeks postpartum, and 19 of them (14.0%) had PPD. Of the 19 participants with PPD, 9 met the EPDS criterion only, 3 met the PHQ-9 criterion only, and 7 met both criteria. OT levels were not significantly different between those with and without PPD (p = 0.35). CRH levels (aOR = 1.011, 95% CI = 1.001-1.023, p = 0.041), DASS-21 stress (aOR = 1.259, 95% CI = 1.132-1.400, p < 0.001), and APGAR at 1 min (aOR = 0.425, 95% CI = 0.240-0.752, p = 0.003) were significant predictors of PPD. CONCLUSIONS: Only high CRH but not OT levels in late pregnancy may predict 6-week PPD. However, combining these CRH levels, late pregnancy stress, and newborn well-being immediately after birth seems to increase the accuracy of PPD prediction.

Experiences Shape Hippocampal Neuron Morphology and the Local Levels of CRHR1 and OTR.

The dorsal hippocampus is involved in behavioral avoidance regulation. It is unclear how experiences such as the neonatal stress of maternal deprivation (MD) and post-weaning environmental enrichment (EE) affect avoidance behavior and the dorsal hippocampal parameters, including neuronal morphology, corticotrophin-releasing hormone (CRH) signaling, and oxytocin receptor (OTR) level. In male BALB/c mice, we found that MD impaired avoidance behavior in the step-on test compared to non-MD and EE rearing conditions could alleviate that partially. MD increased neuronal branches in the CA1 but decreased synaptic connection levels in the CA2, CA3, and DG. Meanwhile, MD increased the CA1's OTR levels, which negatively correlated with nucleus densities. MD also increased the CA1's and CA2's CRH levels, which positively correlated with CRHR1 levels. However, MD statistically elevated the CA3's CRH receptor 1 (CRHR1) levels, which negatively correlated with nucleus densities and, probably, synaptic connection levels in the CA3. The additive effects of MD and EE maintained similar CRH levels and CRHR1 levels as well as OTR levels in the hippocampal areas as the additive of non-MD and non-EE. However, the presence of MD and EE still decreased the CA1's neuronal branches and the CA2's and DG's synaptic connection levels. The study illustrates how MD and EE affect avoidance behaviors, hippocampal neuron morphology, and CRH and OTR levels. The results indicate that the late-life environmental improvement partially restores the alterations in dorsal hippocampal areas induced by early life stress.

Preterm Birth and Corticotrophin-Releasing Hormone as a Placental Clock.

Preterm birth worldwide remains a significant cause of neonatal morbidity and mortality, yet the exact mechanisms of preterm parturition remain unclear. Preterm birth is not a single condition, but rather a syndrome with a multifactorial etiology. This multifactorial nature explains why individual predictive measures for preterm birth have had limited sensitivity and specificity. One proposed pathway for preterm birth is via placentally synthesized corticotrophin-releasing hormone (CRH). CRH is a peptide hormone that increases exponentially in pregnancy and has been implicated in preterm birth because of its endocrine, autocrine, and paracrine roles. CRH has actions that increase placental production of estriol and of the transcription factor nuclear factor-κB, that likely play a key role in activating the myometrium. CRH has been proposed as part of a placental clock, with early activation of placental production resulting in preterm birth. This article will review the current understanding of preterm birth, CRH as an initiator of human parturition, and the evidence regarding the use of CRH in the prediction of preterm birth.

The mastery lifestyle intervention to reduce biopsychosocial risks for pregnant Latinas and African Americans and their infants: protocol for a randomized controlled trial.

BACKGROUND: Pregnant Mexican Americans (hereafter called Latinas) and Black/African American women are at increased risk for psychological distress, contributing to preterm birth and low birthweight; acculturative stress combined with perceived stress elevates depressive symptoms in Latinas. Based on our prior research using a psychoneuroimmunology framework, we identified psychological and neuroendocrine risk factors as predictors of preterm birth in Latina women that are also identified as risk factors for Black/African American women. METHODS/DESIGN: In this prospective, randomized controlled trial with parallel group design we will explore psychosocial, neuroendocrine, and birth outcome effects of the Mastery Lifestyle Intervention (MLI). The MLI is a culturally relevant, manualized, psychosocial, group intervention integrating two cognitive behavioral therapies for both pregnant Latinas and Black/African American women (total n = 221). Study inclusion criteria are: women with current pregnancy at 14-20 weeks gestation, ability to read and speak English or Spanish, self-identify as Latina of Mexican heritage or Black/African American, 18-45 years old, born in the US or Mexico, and currently living in the US. Participants must receive Medicaid or other government-supported insurance, and meet screening criteria for anxiety, depressive symptoms, or stress. Participants are randomly assigned to either the intervention (MLI) or usual care group (UCG) in groups of 6-8 participants that occur over 6 consecutive weeks. Data are collected at 3 time points: enrollment (14-20 weeks gestation), following treatment (20-26 weeks), and 6 weeks after treatment (32-36 weeks gestation). Additional outcome, mediating, and moderating data are collected from the electronic health record during pregnancy and at birth. Analyses will primarily use generalized linear mixed modeling (GLMM) to evaluate the relationships between predictors and outcomes. DISCUSSION: This RCT will test the efficacy of two combined third generation cognitive behavioral therapies (the MLI), given in a group format over 6 sessions, as compared to a usual prenatal care group, for both Latina and African American pregnant women. If efficacious, it may be provided as an adjunct to routine prenatal care and improve mental health, as well as babies being born too small and too soon. TRIAL REGISTRATION: The trial was retrospectively registered at ClinicalTrials.gov . Bethesda (MD): National Library of Medicine. Identifier NCT05012072 , Reducing Pregnancy Risks: The Mastery Lifestyle Intervention (MLI); August 19, 2021. The trial is currently recruiting participants.

The Value of HPA Axis Hormones as Biomarkers for Screening and Early Diagnosis of Postpartum Depression: Updated Information About Methodology.

Because of the high prevalence of postpartum depression (PPD) and the suffering involved, early diagnosis is urgent; however, current screening tools and diagnosis are inadequate. In addition to conventional methods such as the Edinburgh Postnatal Depression Scale and clinical interviews, several hormones in the hypothalamic-pituitary-adrenal (HPA) axis, such as corticotrophin-releasing hormone, adrenocorticotropic hormone, and cortisol, have been considered because of their critical roles in stress regulation in the mothers. The study designs are complicated, however, and so the effectiveness of these hormones as biomarkers for PPD is still controversial. Such inconsistency may have resulted from the variation in methodology between studies. The methodology problems in the investigation of PPD and HPA axis hormones have not been reported extensively. We therefore sought to summarize the methodological problems of studies published in the past decade, including the strengths and weaknesses of the examinations and the technological difficulties involved. Our findings suggest that (a) suitable samples and appropriate detection methods would reduce heterogeneity among trials; (b) the cutoff value of the scale test should be carefully selected for determining the performance of biomarker tests; (c) evaluation methods and criteria should be chosen with consideration of the tools feasible for use in local hospitals and population; and (d) the cost of diagnosis should be reduced. We hope that these findings provide insight for future investigations of HPA axis hormones as biomarkers for screening and early diagnosis of PPD.

Pregnancy anxiety, placental corticotropin-releasing hormone and length of gestation.

OBJECTIVE: High pregnancy anxiety is a consistent predictor of earlier labor and delivery. Placental corticotropin-releasing hormone (pCRH) predicts earlier delivery consistently and it has been identified as a biological mediator of the association between pregnancy anxiety and gestational length. However, studies have not examined whether changes in pregnancy anxiety are associated with earlier birth as mediated by changes in pCRH during pregnancy. Accordingly, this study tests whether linear changes in pregnancy anxiety are associated with length of gestation indirectly through nonlinear increases in pCRH over pregnancy. METHODS: A sample of pregnant women (n=233) completed prenatal assessments in early pregnancy, second trimester, and third trimester that included a 4-item assessment of pregnancy anxiety and collection of blood samples assayed for pCRH using radioimmunoassay. Length of gestation was abstracted from medical records after birth. RESULTS: Increases in pregnancy anxiety from early pregnancy to third trimester predicted shorted length of gestation, as did nonlinear increases in pCRH over pregnancy. However, there was no evidence of an indirect effect of changes in pregnancy anxiety on length of gestation via changes in pCRH. CONCLUSIONS: These results indicate that linear changes in pregnancy anxiety and nonlinear changes in pCRH during pregnancy are independent risk factors for shortened gestational length. This study adds to a small but growing body of work on biopsychological processes in pregnancy and length of gestation. Modeling changes in psychological and biological processes during pregnancy could provide more insight into understanding risk for adverse pregnancy outcomes.

Upregulated Angiotensin Ia Receptors in the Hypothalamic Paraventricular Nucleus Sensitize Neuroendocrine Vasopressin Release and Blood Pressure in a Rodent Model of Polycystic Kidney Disease.

INTRODUCTION: Angiotensin (Ang) II signalling in the hypothalamic paraventricular nucleus (PVN) via Ang type-1a receptors (AT1R) regulates vasopressin release and sympathetic nerve activity - two effectors of blood pressure regulation. We determined the cellular expression and function of AT1R in the PVN of a rodent model of polycystic kidney disease (PKD), the Lewis polycystic kidney (LPK) rat, to evaluate its contribution to blood pressure regulation and augmented vasopressin release in PKD. METHODS: PVN AT1R gene expression was quantified with fluorescent in situ hybridization in LPK and control rats. PVN AT1R function was assessed with pharmacology under urethane anaesthesia in LPK and control rats instrumented to record arterial pressure and sympathetic nerve activity. RESULTS: AT1R gene expression was upregulated in the PVN, particularly in corticotrophin-releasing hormone neurons, of LPK versus control rats. PVN microinjection of Ang II produced larger increases in systolic blood pressure in LPK versus control rats (36 ± 5 vs. 17 ± 2 mm Hg; p < 0.01). Unexpectedly, Ang II produced regionally heterogeneous sympathoinhibition (renal: -33%; splanchnic: -12%; lumbar: no change) in LPK and no change in controls. PVN pre-treatment with losartan, a competitive AT1R antagonist, blocked the Ang II-mediated renal sympathoinhibition and attenuated the pressor response observed in LPK rats. The Ang II pressor effect was also blocked by systemic OPC-21268, a competitive V1A receptor antagonist, but unaffected by hexamethonium, a sympathetic ganglionic blocker. DISCUSSION/CONCLUSION: Collectively, our data suggest that upregulated AT1R expression in PVN sensitizes neuroendocrine release of vasopressin in the LPK, identifying a central mechanism for the elevated vasopressin levels present in PKD.

Unraveling the role of Epac1-SOCS3 signaling in the development of neonatal-CRD-induced visceral hypersensitivity in rats.

AIMS: Visceral hypersensitivity in irritable bowel syndrome (IBS) is widespread, but effective therapies for it remain elusive. As a canonical anti-inflammatory protein, suppressor of cytokine signaling 3 (SOCS3) reportedly relays exchange protein 1 directly activated by cAMP (Epac1) signaling and inhibits the intracellular response to inflammatory cytokines. Despite the inhibitory effect of SOCS3 on the pro-inflammatory response and neuroinflammation in PVN, the systematic investigation of Epac1-SOCS3 signaling involved in visceral hypersensitivity remains unknown. This study aimed to explore Epac1-SOCS3 signaling in the activity of hypothalamic paraventricular nucleus (PVN) corticotropin-releasing factor (CRF) neurons and visceral hypersensitivity in adult rats experiencing neonatal colorectal distension (CRD). METHODS: Rats were subjected to neonatal CRD to simulate visceral hypersensitivity to investigate the effect of Epac1-SOCS3 signaling on PVN CRF neurons. The expression and activity of Epac1 and SOCS3 in nociceptive hypersensitivity were determined by western blot, RT-PCR, immunofluorescence, radioimmunoassay, electrophysiology, and pharmacology. RESULTS: In neonatal-CRD-induced visceral hypersensitivity model, Epac1 and SOCS3 expressions were downregulated and IL-6 levels elevated in PVN. However, infusion of Epac agonist 8-pCPT in PVN reduced CRF neuronal firing rates, and overexpression of SOCS3 in PVN by AAV-SOCS3 inhibited the activation of PVN neurons, reduced visceral hypersensitivity, and precluded pain precipitation. Intervention with IL-6 neutralizing antibody also alleviated the visceral hypersensitivity. In naïve rats, Epac antagonist ESI-09 in PVN increased CRF neuronal firing. Consistently, genetic knockdown of Epac1 or SOCS3 in PVN potentiated the firing rate of CRF neurons, functionality of HPA axis, and sensitivity of visceral nociception. Moreover, pharmacological intervention with exogenous IL-6 into PVN simulated the visceral hypersensitivity. CONCLUSIONS: Inactivation of Epac1-SOCS3 pathway contributed to the neuroinflammation accompanied by the sensitization of CRF neurons in PVN, precipitating visceral hypersensitivity and pain in rats experiencing neonatal CRD.

Mineralocorticoid receptor and glucocorticoid receptor work alone and together in cell-type-specific manner: Implications for resilience prediction and targeted therapy.

'You can't roll the clock back and reverse the effects of experiences' Bruce McEwen used to say when explaining how allostasis labels the adaptive process. Here we will for once roll the clock back to the times that the science of the glucocorticoid hormone was honored with a Nobel prize and highlight the discovery of their receptors in the hippocampus as inroad to its current status as master regulator in control of stress coping and adaptation. Glucocorticoids operate in concert with numerous neurotransmitters, neuropeptides, and other hormones with the aim to facilitate processing of information in the neurocircuitry of stress, from anticipation and perception of a novel experience to behavioral adaptation and memory storage. This action, exerted by the glucocorticoids, is guided by two complementary receptor systems, mineralocorticoid receptors (MR) and glucocorticoid receptors (GR), that need to be balanced for a healthy stress response pattern. Here we discuss the cellular, neuroendocrine, and behavioral studies underlying the MR:GR balance concept, highlight the relevance of hypothalamic-pituitary-adrenal (HPA) -axis patterns and note the limited understanding yet of sexual dimorphism in glucocorticoid actions. We conclude with the prospect that (i) genetically and epigenetically regulated receptor variants dictate cell-type-specific transcriptome signatures of stress-related neuropsychiatric symptoms and (ii) selective receptor modulators are becoming available for more targeted treatment. These two new developments may help to 'restart the clock' with the prospect to support resilience.

Desmopressin Stimulation Test in a Pregnant Patient with Cushing's Disease.

Objective: Hypothalamic-pituitary-adrenal axis stimulation during pregnancy complicates the investigation of Cushing's syndrome (CS). Our objective was to present the case of a pregnant patient with CS caused by a pituitary tumor in whom the desmopressin stimulation test helped in the diagnosis and led to appropriate management. Case Report: A 27-year-old woman with 9-week gestation presented with a 2-month history of proximal myopathy. She had high blood pressure, wide purplish striae, and a 1-year history of hypertension and dysglycemia. The 8 am cortisol level was 32.4 µg/dL (normal, 5-18 µg/dL), late-night salivary cortisol level was 0.7 µg/dL (11 pm, normal, <0.4 µg/dL), 24-hour urinary free cortisol levels were 237.6 µg/d (normal, 21.0-143.0 µg/d), and adrenocorticotropic hormone (ACTH) levels were 44.0 pg/mL (8 am, normal, 0-46.0 pg/mL). Nongadolinium-enhanced pituitary magnetic resonance imaging revealed no obvious lesion. The desmopressin stimulation test showed a 70% increase in ACTH levels from baseline after desmopressin administration. Pituitary magnetic resonance imaging with gadolinium revealed an 8 × 8 × 7-mm3 pituitary adenoma. Transsphenoidal surgery was performed, which revealed the presence of ACTH-positive tumor cells. After tumor removal, the patient carried on pregnancy uneventfully. Discussion: During pregnancy, ACTH levels may not be an accurate marker to help in the differential diagnosis of CS. Moreover, nongadolinium pituitary imaging might not detect small pituitary lesions. Conclusion: In the present case, the desmopressin stimulation test suggested the diagnosis of Cushing's disease, which subsequently led to successful treatment. This suggests that the desmopressin test serves as a useful test for diagnosing Cushing's disease in pregnant individuals.

Glutamate attenuates lipopolysaccharide induced intestinal barrier injury by regulating corticotropin-releasing factor pathway in weaned pigs.

OBJECTIVE: The purpose of this study was to evaluate the protection of glutamate (GLU) against the impairment in intestinal barrier function induced by lipopolysaccharide (LPS) stress in weaned pigs. METHODS: Twenty-four weaned pigs were divided into four treatments containing: i) non-challenged control, ii) LPS-challenged control, iii) LPS+1.0% GLU, and iv) LPS+2.0% GLU. On day 28, pigs were treated with LPS or saline. Blood samples were collected at 0, 2, and 4 h post-injection. After blood samples collection at 4 h, all pigs were slaughtered, and spleen, mesenteric lymph nodes, liver and intestinal samples were obtained. RESULTS: Dietary GLU supplementation inhibited the LPS-induced oxidative stress in pigs, as demonstrated by reduced malondialdehyde level and increased glutathione level in jejunum. Diets supplemented with GLU enhanced villus height, villus height/crypt depth and claudin-1 expression, attenuated intestinal histology and ultrastructure impairment induced by LPS. Moreover, GLU supplementation reversed intestinal intraepithelial lymphocyte number decrease and mast cell number increase induced by LPS stress. GLU reduced serum cortisol concentration at 4 h after LPS stress and downregulated the mRNA expression of intestinal corticotropin-releasing factor signal (corticotrophin-releasing factor [CRF], CRF receptor 1 [CRFR1], glucocorticoid receptor, tryptase, nerve growth factor, tyrosine kinase receptor A), and prevented mast cell activation. GLU upregulated the mRNA expression of intestinal transforming growth factor ß. CONCLUSION: These findings indicate that GLU attenuates LPS-induced intestinal mucosal barrier injury, which is associated with modulating CRF signaling pathway.

The hypothalamic paraventricular nucleus as a central hub for the estrogenic modulation of neuroendocrine function and behavior.

Estradiol and hypothalamic paraventricular nucleus (PVN) help coordinate reproduction with body physiology, growth and metabolism. PVN integrates hormonal and neural signals originating in the periphery, generating an output mediated both by its long-distance neuronal projections, and by a variety of neurohormones produced by its magnocellular and parvocellular neurosecretory cells. Here we review the cyto-and chemo-architecture, the connectivity and function of PVN and the sex-specific regulation exerted by estradiol on PVN neurons and on the expression of neurotransmitters, neuromodulators, neuropeptides and neurohormones in PVN. Classical and non-classical estrogen receptors (ERs) are expressed in neuronal afferents to PVN and in specific PVN interneurons, projecting neurons, neurosecretory neurons and glial cells that are involved in the input-output integration and coordination of neurohormonal signals. Indeed, PVN ERs are known to modulate body homeostatic processes such as autonomic functions, stress response, reproduction, and metabolic control. Finally, the functional implications of the estrogenic modulation of the PVN for body homeostasis are discussed.

Behavioral, neurochemical, and neuroimmune changes associated with social buffering and stress contagion.

Social buffering can provide protective effects on stress responses and their subsequent negative health outcomes. Although social buffering is beneficial for the recipient, it can also have anxiogenic effects on the provider of the social buffering - a phenomena referred to as stress contagion. Social buffering and stress contagion usually occur together, but they have traditionally been studied independently, thus limiting our understanding of this dyadic social interaction. In the present study, we examined the effects of preventative social buffering and stress contagion in socially monogamous prairie voles (Microtus ochrogaster). We tested the hypothesis that this dynamic social interaction is associated with coordinated alterations in behaviors, neurochemical activation, and neuroimmune responses. To do so, adult male prairie voles were stressed via an acute immobilization restraint tube (IMO) either alone (Alone) or with their previously pair-bonded female partner (Partner) in the cage for 1 h. In contrast, females were placed in a cage containing either an empty IMO tube (Empty) or one that contained their pair-bonded male (Partner). Anxiety-like behavior was tested on the elevated plus maze (EPM) following the 60-mins test and brain sections were processed for neurochemical/neuroimmune marker labeling for all subjects. Our data indicate that females in the Partner group were in contact with and sniffed the IMO tube more, showed fewer anxiety-like behaviors, and had a higher level of oxytocin expression in the paraventricular nucleus of the hypothalamus (PVN) compared to the Empty group females. Males in the Partner group had lower levels of anxiety-like behavior during the EPM test, greater activation of corticotropin-releasing hormone expressing neurons in the PVN, lower activation of serotonin neurons in the dorsal raphe, and lower levels of microgliosis in the nucleus accumbens. Taken together, these data suggest brain region- and neurochemical-specific alterations as well as neuroinflammatory changes that may be involved in the regulation of social buffering and stress contagion behaviors.

Exercise-Induced Adrenocorticotropic Hormone Response Is Cooperatively Regulated by Hypothalamic Arginine Vasopressin and Corticotrophin-Releasing Hormone.

INTRODUCTION: Exercise becomes a stress when performed at an intensity above the lactate threshold (LT) because at that point the plasma adrenocorticotropic hormone (ACTH), a marker of stress response, increases. It is possible that the exercise-induced ACTH response is regulated at least by arginine vasopressin (AVP) and possibly by corticotropin-releasing hormone (CRH), but this remains unclear. To clarify the involvement of these factors, it is useful to intervene pharmacologically in the regulatory mechanisms, with a physiologically acceptable exercise model. METHODS: We used a special stress model of treadmill running (aerobic exercise) for male Wistar rats, which mimic the human physiological response, where plasma ACTH levels increase at just above the LT for 30 min. Animals were administered the AVP V1b receptor antagonist SSR149415 (SSR) and/or the CRH type 1 receptor antagonist CP154526 (CP) intraperitoneally before the exercise, which allowed the monitoring of exercise-induced ACTH response. Immunohistochemical evaluation of activated AVP and CRH neurons with exercise was performed for the animals' hypothalami. RESULTS: A single injection of either antagonist, SSR or CP, resulted in inhibited ACTH levels after exercise stress. Moreover, the combined injection of SSR and CP strongly suppressed ACTH secretion during treadmill running to a greater extent than each alone. The running-exercise-induced activation of both AVP and CRH neurons in the hypothalamus was also confirmed. CONCLUSION: These results lead us to hypothesize that AVP and CRH are cooperatively involved in exercise-induced ACTH response just above the LT. This may also reflect the stress response with moderate-intensity exercise in humans.

Mediatory role of the central NPY, melanocortine and corticotrophin systems on phoenixin-14 induced hyperphagia in neonatal chicken.

Animal research indicates the neuropeptide Y (NPY), corticotrophin and melanocortin systems have a mediatory role in reward, however, how these substances interact with phenytoin-14 (PNX-14) induced food intake in birds remains to be identified. Accordingly, in this research eight tests were carried out to investigate the potential interactions of the NPY, melanocortin, as well as corticotrophin systems with PNX-14 on food consumption in neonatal chickens. In the first experiment, chickens were intracerebroventricular (ICV) injected with phosphate-buffered saline (PBS) and PNX-14 (0.8, 0.16, and 3.2 nmol). In second experiment, PBS, the antagonist of CRF1/CRF2 receptors (astressin-B, 30 µg) and PNX-14 + astressin-B were injected. In the rest of the experiments chicken received astressin2-B (CRF2 receptor antagonist; 30 µg), SHU9119 (MCR3/MCR4 receptor antagonist, 0.5nomol), MCL0020 (MCR4 receptor agonist, 0.5 nmol), B5063 (NPY1 receptor antagonist, 1.25 µg), SF22 (NPY2 receptor antagonist, 1.25 µg) and SML0891 (NPY5 receptor antagonist, 1.25 µg) rather than astressin-B. Then, cumulative intake of food was recorded for 2 h. Based on the findings, PNX-14 (0.16 and 3.2 nmol) led to increment in food consumption compared with the control (P < 0.05). Co-administration of the PNX-14 and astressin-B promoted PNX-14-induced hyperphagia (P < 0.05). Co-injection of the PNX-14 + astressin2-B potentiated hyperphagia PNX-14 (P < 0.05). Co-injection of PNX-14 + B5063 inhibited the effects of the PNX-14 (P < 0.05). The co-administration of the PNX-14 and SML0891 potentiated hypophagic effects of the PNX-14 (P < 0.05). The results showed that PNX-14-induced hyperphagia mediates via NPY1, NPY5, and CRF1/CRF2 receptors in neonatal chickens.

Serum Corticotrophin Releasing Factor (CRF) and its correlation with stress and craving in detoxified opioid-dependent subjects.

Corticotrophin Releasing Factor (CRF) might be suitable as biological measure of stress as it is implicated directly in both central neurological and endocrine stress-response. The study aims to compare serum CRF levels and perceived stress in opioid-dependent subjects (n = 53) with non-using controls (n = 47) and to correlate them with general and instantaneous craving (in cases only). Perceived stress score and serum CRF levels were significantly higher among the users. No significant correlation with craving was found. The significant difference in serum CRF levels indicate feasibility of measuring CRF levels in peripheral fluids and asserts its role as biochemical measure of stress.