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Purpose: Research supports physical activity as a method to heighten stress resistance and resilience through positive metabolic alterations mostly affecting the neuroendocrine system. High-intensity interval training (HIIT) has been proposed as a highly effective time-saving method to induce those changes. However, existing literature relies heavily on cross-sectional analyses, with few randomised controlled trials highlighting the necessity for more exercise interventions. Thus, this study aims to investigate the effects of HIIT versus an active control group on the stress response to an acute psychosocial stressor in emotionally impulsive humans (suggested as being strong stress responders). Methods: The study protocol was registered online (DRKS00016589) before data collection. Sedentary, emotionally impulsive adults (30.69 ± 8.20 y) were recruited for a supervised intervention of 8 weeks and randomly allocated to either a HIIT (n = 25) or a stretching group (n = 19, acting as active controls). Participants were submitted to a test battery, including saliva samples, questionnaires (self-efficacy- and perceived stress-related), visual analogue scales (physical exercise- and stress-related), and resting electroencephalography and electrocardiography assessing their reaction to an acute psychological stressor (Trier Social Stress Test) before and after the exercise intervention. Results: HIIT increased aerobic fitness in all participants, whereas stretching did not. Participants from the HIIT group reported perceiving exercising more intensively than those from the active control group (ƞp2 = 0.108, p = 0.038). No further group differences were detected. Both interventions largely increased levels of joy post-TSST (ƞp2 = 0.209, p = 0.003) whilst decreasing tension (ƞp2 = 0.262, p < 0.001) and worries (ƞp2 = 0.113, p = 0.037). Finally, both interventions largely increased perceived levels of general self-efficacy (ƞp2 = 0.120, p = 0.029). Conclusion: This study suggests that 8 weeks of HIIT does not change the psychoneuroendocrine response to an acute psychological stress test compared to an active control group in emotionally impulsive humans. Further replications of supervised exercise studies highly powered with active and passive controls are warranted. [ABSTRACT FROM AUTHOR]

The bidirectional relationship between the gut microbiota and the nervous system is known as the microbiota–gut–brain axis (MGBA). The MGBA controls the complex interactions between the brain, the enteric nervous system, the gut-associated immune system, and the enteric neuroendocrine systems, regulating key physiological functions such as the immune response, sleep, emotions and mood, food intake, and intestinal functions. Psychobiotics are considered tools with the potential to modulate the MGBA through preventive, adjunctive, or curative approaches, but their specific mechanisms of action on many aspects of health are yet to be characterized. This narrative review and perspectives article highlights the key paradigms needing attention as the scope of potential probiotics applications in human health increases, with a growing body of evidence supporting their systemic beneficial effects. However, there are many limitations to overcome before establishing the extent to which we can incorporate probiotics in the management of neuropsychiatric disorders. Although this article uses the term probiotics in a general manner, it remains important to study probiotics at the strain level in most cases. [ABSTRACT FROM AUTHOR]

• Psychological stress is a crucial factor in the development of many skin diseases. • Psychological stress can worsen skin diseases and affect patients' quality of life. • Stress impacts skin diseases through the HPA axis, SNS, and neuropeptides. Psychological stress is a crucial factor in the development of many skin diseases, and the stigma caused by skin disorders may further increase the psychological burden, forming a vicious cycle of psychological stress leading to skin diseases. Therefore, understanding the relationship between stress and skin diseases is necessary. The skin, as the vital interface with the external environment, possesses its own complex immune system, and the neuroendocrine system plays a central role in the stress response of the body. Stress-induced alterations in the immune system can also disrupt the delicate balance of immune cells and inflammatory mediators in the skin, leading to immune dysregulation and increased susceptibility to various skin diseases. Stress can also affect the skin barrier function, impair wound healing, and promote the release of pro-inflammatory cytokines, thereby exacerbating existing skin diseases such as psoriasis, atopic dermatitis, acne, and urticaria. In the present review, we explored the intricate relationship between stress and skin diseases from a neuroendocrine-immune interaction perspective. We explored the occurrence and development of skin diseases in the context of stress, the stress models for skin diseases, the impact of stress on skin function and diseases, and relevant epidemiological studies and clinical trials. Understanding the relationship between stress and skin diseases from a neuroendocrine-immune interaction perspective provides a comprehensive framework for targeted interventions and new insights into the diagnosis and treatment of skin diseases. [ABSTRACT FROM AUTHOR]

Allostasis provides a supporting role to the homeostatic control of biological variables in mammalian species. While the concept of homeostasis is related to the control of variables within a set point or range that are essential to life, allostasis refers to systems that facilitate adaptation to challenges that the organism faces and the new requirements for survival. Essential for such adaptation is the role played by the brain in eliciting neural and neuroendocrine responses. Reproductive function is fundamental for the survival of species but is costly in energetic terms and requires a synchrony with an ever-changing environment. Thus, in many species reproductive function is blocked or delayed over immediate challenges. This review will cover the physiological systems and neuroendocrine pathways that supply allostatic control over reproductive neuroendocrine systems. Light, hypoxia, temperature, nutrition, psychosocial, and immune mediators influence the neuroendocrine control of reproductive functions through pathways that are confluent at the paraventricular nucleus; however, understanding of the integrative responses to these stimuli has not been clarified. Likely, the ultimate consequence of these allostatic mechanisms is the modification of kisspeptin and gonadotropin-releasing hormone neuronal activity, thus compromising reproduction function in the short term, while preserving species survivability. [ABSTRACT FROM AUTHOR]

Cognitive function in humans depends on the complex and interplay between multiple body systems, including the hypothalamic-pituitary-adrenal (HPA) axis. The gut microbiota, which vastly outnumbers human cells and has a genetic potential that exceeds that of the human genome, plays a crucial role in this interplay. The microbiota-gut-brain (MGB) axis is a bidirectional signalling pathway that operates through neural, endocrine, immune, and metabolic pathways. One of the major neuroendocrine systems responding to stress is the HPA axis which produces glucocorticoids such as cortisol in humans and corticosterone in rodents. Appropriate concentrations of cortisol are essential for normal neurodevelopment and function, as well as cognitive processes such as learning and memory, and studies have shown that microbes modulate the HPA axis throughout life. Stress can significantly impact the MGB axis via the HPA axis and other pathways. Animal research has advanced our understanding of these mechanisms and pathways, leading to a paradigm shift in conceptual thinking about the influence of the microbiota on human health and disease. Preclinical and human trials are currently underway to determine how these animal models translate to humans. In this review article, we summarize the current knowledge of the relationship between the gut microbiota, HPA axis, and cognition, and provide an overview of the main findings and conclusions in this broad field. [ABSTRACT FROM AUTHOR]

Stressful life experiences are associated with the development of neuropsychiatric disorders like depression. Emerging evidence indicates that microglia, the specialized resident macrophages of the brain, may be a key mediator of the relationship between psychosocial stressor exposure and adaptive or maladaptive responses at the level of synaptic, circuit, and neuroimmune alterations. Here, we review current literature regarding how psychosocial stressor exposure changes microglial structure and function, thereby altering behavioral and brain outcomes, with a particular focus on age- and sex-dependent effects. We argue that additional emphasis should be placed in future research on investigating sex differences and the impacts of stressor exposure during sensitive periods of development, as well as going beyond traditional morphological measurements to interrogate microglial function. The bidirectional relationship between microglia and the stress response, particularly the role of microglia in the neuroendocrine control of stress-related circuits, is also an important area for future investigation. Finally, we discuss emerging themes and future directions that point to the possibility of the development of novel therapeutics for stress-related neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]

Cancer cells can produce and release biogenic amines, melatonin, neurotransmitters, neuropeptides, neurohormones, and glucocorticoids. Cancer-derived mediators can stimulate main neuroendocrine centers such as the hypothalamus, pituitary, adrenals, and thyroid to regulate body homeostasis. Cancer-derived neurotransmitters and neurohormones can affect brain functions and disrupt biological rhythms and systemic autoregulatory networks. We hypothesize that tumors use neuroendocrine and immune systems to set the body in a homeostatic mode favoring the tumor's expansion. During oncogenesis, cancer not only escapes the body's regulatory mechanisms, but also gains the ability to affect local and systemic homeostasis. Specifically, tumors produce cytokines, immune mediators, classical neurotransmitters, hypothalamic and pituitary hormones, biogenic amines, melatonin, and glucocorticoids, as demonstrated in human and animal models of cancer. The tumor, through the release of these neurohormonal and immune mediators, can control the main neuroendocrine centers such as the hypothalamus, pituitary, adrenals, and thyroid to modulate body homeostasis through central regulatory axes. We hypothesize that the tumor-derived catecholamines, serotonin, melatonin, neuropeptides, and other neurotransmitters can affect body and brain functions. Bidirectional communication between local autonomic and sensory nerves and the tumor, with putative effects on the brain, is also envisioned. Overall, we propose that cancers can take control of the central neuroendocrine and immune systems to reset the body homeostasis in a mode favoring its expansion at the expense of the host. [ABSTRACT FROM AUTHOR]

Trehalose is a major circulatory sugar in the haemolymph of insects. It provides instant energy and protection against stress. Trehalose metabolism is associated with insect growth and development. The architecture and spatio-temporal expression dynamics of trehalose metabolism and transport genes are key for regulation. These genes are controlled by various transcription factors, largely linked to nutrition, insect development, and metamorphosis. Also, trehalose levels are affected by substrate affinities and modifications of enzymes involved in the pathway. A feedback mechanism involving the precursors and products can regulate trehalose metabolism. Further, the neuroendocrine system controls trehalose levels under normal and stressed conditions by producing different hormones. Hypotrehalosemic hormones work under surplus energy conditions to activate haemolymph trehalose uptake and degradation. In contrast, hypertrehalosemic hormones stimulate trehalose production in the fat body and its transport to the haemolymph. However, trehalose metabolism regulation in insects needs to be studied in detail. This review discusses aspects of trehalose synthesis, transport, and degradation dynamics in developmental transition and stress response. Unraveling the epigenetic factors, transcriptional control and chemical or genetic modulators can provide further insights into the intricate regulation of trehalose in a development- and tissue-specific manner. This molecular information about effectors and regulators of trehalose metabolism can be applied in developing diverse biotechnological applications. [ABSTRACT FROM AUTHOR]

Mollusks comprise one of the largest phylum of marine invertebrates. With their great diversity of species, various degrees of mobility, and specific behavioral strategies, they haveoccupied marine, freshwater, and terrestrial habitats and play key roles in many ecosystems. This success is explained by their exceptional ability to tolerate a wide range of environmental stresses, such as hypoxia. Most marine bivalvemollusksare exposed to frequent short-term variations in oxygen levels in their marine or estuarine habitats. This stressfactor has caused them to develop a wide variety of adaptive strategies during their evolution, enabling to mobilize rapidly a set of behavioral, physiological, biochemical, and molecular defenses that re-establishing oxygen homeostasis. The neuroendocrine system and its related signaling systems play crucial roles in the regulation of various physiological and behavioral processes in mollusks and, hence, can affect hypoxiatolerance. Little effort has been made to identify the neurotransmitters and genes involved in oxygen homeostasis regulation, and the molecular basis of the differences in the regulatory mechanisms of hypoxia resistance in hypoxia-tolerant and hypoxia-sensitive bivalve species. Here, we summarize current knowledge about the involvement of the neuroendocrine system in the hypoxia stress response, and the possible contributions of various signaling molecules to this process. We thusprovide a basis for understanding the molecular mechanisms underlying hypoxic stress in bivalves, also making comparisons with data from related studies on other species. [ABSTRACT FROM AUTHOR]

Background: Human organisms have to cope with a large number of external or internal stressful stimuli that threaten – or are perceived as threatening – their internal dynamic balance or homeostasis. To face these disturbing forces, or stressors, organisms have developed a complex neuroendocrine system, the stress system, which consists of the hypothalamic-pituitary-adrenal axis and the locus caeruleus/norepinephrine-autonomic nervous system. Summary: Upon exposure to stressors beyond a certain threshold, the activation of the stress system leads to a series of physiological and behavioral adaptations that help achieve homeostasis and increase the chances of survival. When, however, the stress response to stressors is inadequate, excessive, or prolonged, the resultant maladaptation may lead to the development of several stress-related pathologic conditions. Adverse environmental events, especially during critical periods of life, such as prenatal life, childhood, and puberty/adolescence, in combination with the underlying genetic background, may leave deep, long-term epigenetic imprints in the human expressed genome. Key Messages: In this review, we describe the components of the stress system and its functional interactions with other homeostatic systems of the organism; we present the hormonal regulators of the stress response, and we discuss the development of stress-related pathologies. [ABSTRACT FROM AUTHOR]

This review aims at defining the neuroendocrine mechanisms underlying the sport-induced restrictions of the reproductive axis in female athletes. Episodic gonadotropin release was found to be compromised, presumably a result of impaired hypothalamic pulsatile GnRH release. Any deviation from optimal gonadotropin release may result in a suboptimal function of the ovaries, leading to disorders of the menstrual cycle and ovulation. A whole spectrum of menstrual dysfunctions ranging from ovulatory eumenorrhea to luteal phase defects and amenorrhea has been reported in sportive women. As essential neuroendocrine factors underlying these observations, activation of the adrenal axis and altered central nervous neurotransmitter activity have been identified to transfer metabolic, nutritional, and stress signals into the hypothalamic GnRH release. The degree by which the neuroendocrine axis governing reproduction is impaired critically depends on the intensity and duration of exercise and the state of training. Other decisive factors may be energy expenditure and availability, nutritional components, and the maturity of the hypothalamic-pituitary-ovarian (HPO) axis when sport activity was initiated. In conclusion, the gradual cessation of reproductive function observed in female athletes may be interpreted as an adaptive mechanism in response to physical and psychological endurance during sport. This sport-induced restriction of reproductive capacity may serve as protection (endogenous contraception) to preserve a woman's health. [ABSTRACT FROM AUTHOR]

Mucosal tissues appear to be more important in fish than in mammals due to living in a microbial-rich aquatic milieu, yet the complex interaction between the immune and the neuroendocrine system in these tissues remains elusive. The aim of this work was to investigate the mucosal immune response in immunized rainbow trout vaccinated with Alpha ject vaccine (bivalent), kept in fresh water (FW) or transferred to seawater (SW), and to evaluate their response to acute stress (chasing). Acute stress resulted in higher levels of plasma cortisol (Sham + Stress and Vaccine + Stress). A similar response was observed in skin mucus, but it was lower in Vaccine + Stress compared with stressed fish. With a few exceptions, minimal alterations were detected in the transcriptomic profile of stress-immune gene in the skin of vaccinated and stressed fish in both FW and SW. In the gills, the stress elicited activation of key stress-immune components (gr1 , mr , β-ar , hsp70 , c3 , lysozyme , α-enolase , nadph oxidase , il1β , il6 , tnfα , il10 and tgfβ1) in FW, but fewer immune changes were induced by the vaccine (nadph oxidase , il6 , tnfα , il10 and igt) in both SW and FW. In the intestine, an array of immune genes was activated by the vaccine particularly those related with B cells (igm , igt) and T cells (cd8α) in FW with no stimulation observed in SW. Therefore, our survey on the transcriptomic mucosal response demonstrates that the immune protection conferred by the vaccine to the intestine is modulated in SW. Overall, our results showed: i) plasma and skin mucus cortisol showed no additional stress effect induced by prolonged SW acclimation, ii) the stress and immune response were different among mucosal tissues which indicates a tissue-specific response to specific antigens/stressor. Further, the results suggest that the systemic immune organs may be more implicated in infectious events in SW (as few changes were observed in the mucosal barriers of immunized fish in SW) than in FW. [Display omitted] • Endocrine and immune system interaction at mucosal level can modulate the mucosal immune response. • Seawater acclimation may modulate the protection conferred by vaccines due to physiological alterations. • The gut exhibited a more pronounced immune response to vaccination in fresh water compared to the gills and skin. • Fish kept in fresh water appeared to have a stronger response to acute stress compared to those in sea water. [ABSTRACT FROM AUTHOR]

The attachment representation (AR) of individuals affects emotional and cognitive information processes and is considered an important modulating factor of neuroendocrine stress responses. The neuropeptide oxytocin is studied as one biomolecular component underpinning this modulation. A validated procedure used in attachment-related research is the Adult Attachment Projective Picture System (AAP). To date, only a limited number of studies investigated oxytocin and neuroendocrine reactivity in the context of an attachment-related stimulus similar to the APP. In this pilot study, N = 26 men of recent fatherhood were exposed to the AAP to classify AR and to investigate salivary changes in oxytocin, cortisol and dehydroepiandrosterone (DHEA) after AAP stimulation. We observed increased oxytocin levels in response to AAP exposure, and this increase was more pronounced in fathers with unresolved/disorganized AR. No significant changes in cortisol and DHEA concentrations were observed in response to AAP administration. Interestingly, differences in basal cortisol levels (before the AAP) also depended on AR classification. Here, the group of men with unresolved/disorganized AR showed higher levels of cortisol compared to fathers with organized AR. To conclude, the finding of increased salivary oxytocin levels in response to the AAP further indicates its validity as an instrument to stimulate the attachment system. [ABSTRACT FROM AUTHOR]

As a global burden, the coronavirus disease 2019 (COVID-19) pandemic is going on spread. It has many clinical manifestations and impacts on humans worldwide. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection causes systemic illness through its known receptor binding to angiotensin-converting enzyme 2 (ACE2) which is expressed in various tissue types in the human body. Its infection and systemic condition lead to physical and psychological stress for the patients. During critical illness, and ongoing inflammation, physical and psychological stress both contribute to the patient's outcome. Pre-existing or underlying psychological conditions also affect COVID-19 patients and . lead to poorer prognosis. Stress causes several imbalances including neurohormonal, pro-inflammatory, and metabolic alteration. Ongoing stress and COVID-19 both increase systemic inflammation through interleukin 6 (IL-6), hyperglycemia, and uncontrolled sympathetic drive. These conditions pile up into the vicious cycle of poor prognosis and even mortality. This review article discusses the mechanism of stress to induce inflammation and hyperglycemia that correlated with the poorer outcome in COVID-19 patients. Because of its important role in COVID-19, approaches should be made to overcome stress and homeostatic imbalance caused by stress conditions in COVID-19 patients. [ABSTRACT FROM AUTHOR]

The impact of early developmental experience on neurobiological pathways that may contribute to the association between diet and behavior have not yet been elucidated. The focus of the current study was to determine whether the impact of prenatal stress (PS) could be mitigated by a diet that stimulates the same neuroendocrine systems influenced by early stress, using a mouse model. Behavioral and genetic approaches were used to assess how a Western-pattern diet (WPD) interacts with PS and sex to impact the expression of anxiety-like behavior in an open-field arena, as well as the expression of the glucocorticoid receptor in the hippocampus, D1 dopamine receptors in the nucleus accumbens, and D2 dopamine receptors in the ventral tegmental area. Overall, the results demonstrated that a prenatal WPD mitigates the effects of maternal stress in dams and offspring. These results help to elucidate the relationship between pre- and post-natal nutrition, gene expression, and behaviors that lead to long-term health effects. [ABSTRACT FROM AUTHOR]

Military operational stress is known to increase adrenal hormones and inflammatory cytokines, while decreasing hormones associated with the anabolic milieu and neuroendocrine system. Less is known about the role of extracellular vesicles (EVs), a form of cell-to-cell communication, in military operational stress and their relationship to circulating hormones. The purpose of this study was to characterize the neuroendocrine, cytokine, and EV response to an intense. 24-h selection course known as the Naval Special Warfare (NSW) Screener and identify associations between EVs and cytokines. Blood samples were collected the morning of and following the NSW Screener in 29 men (18-26 yr). Samples were analyzed for concentrations of cortisol, insulinlike growth factor I (IGF-I), neuropeptide-Y (NPY), brain-derived neurotrophic factor (BDNF), α-klotho, tumor necrosis factor-a (TNFα), and interleukins (IL) -1b, -6, and -10. EVs stained with markers associated with exosomes (CD63), microvesicles (VAMP3), and apoptotic bodies (THSD1) were characterized using imaging flow cytometry and vesicle flow cytometry. The selection event induced significant changes in circulating BDNF (-43.2%), IGF-I (-24.6%), TNFα (+17.7%), and IL-6 (+13.6%) accompanied by increases in intensities of THSD1+ and VAMP3+ EVs (all P < 0.05). Higher concentrations of IL-1β and IL-10 were positively associated with THSD1+ EVs (P < 0.05). Military operational stress altered the EV profile. Surface markers associated with apoptotic bodies were positively correlated with an inflammatory response. Future studies should consider a multiomics assessment of EV cargo to discern canonical pathways that may be mediated by EVs during military stress. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests that physiological distress is highly correlated with cancer incidence and mortality. However, the mechanisms underlying psychological challenges‐mediated tumor immune evasion are not systematically explored. Here, it is demonstrated that acute restraint (AR) increases the level of the plasma neuropeptide hormones, kisspeptin, and the expression levels of its receptor, Gpr54, in the hypothalamus, splenic and tumor‐infiltrating T cells, suggesting a correlation between the neuroendocrine system and tumor microenvironment. Accordingly, administration of kisspeptin‐10 significantly impairs T cell function, whereas knockout of Gpr54 in T cells inhibits lung tumor progression by suppressing T cell dysfunction and exhaustion with or without AR. In addition, Gpr54 defective OT‐1 T cells show superior antitumor activity against OVA peptide‐positive tumors. Mechanistically, ERK5‐mediated NR4A1 activation is found to be essential for kisspeptin/GPR54‐facilitated T cell dysfunction. Meanwhile, pharmacological inhibition of ERK5 signaling by XMD8‐92 significantly reduces the tumor growth by enhancing CD8+ T cell antitumor function. Furthermore, depletion of GPR54 or ERK5 by CRISPR/Cas9 in CAR T cells intensifies the antitumor responses to both PSMA+ and CD19+ tumor cells, while eliminating T cell exhaustion. Taken together, these results indicate that kisspeptin/GPR54 signaling plays a nonredundant role in the stress‐induced tumor immune evasion. [ABSTRACT FROM AUTHOR]

Objectives: This narrative review article provides an overview on the involvement of microglia and the hypothalamic-pituitary-adrenal (HPA) axis in the pathophysiology of depression, as well investigates the mutual relationship between these two entities: how microglial activation can contribute to the dysregulation of the HPA axis, and vice versa. Methods: Relevant studies and reviews already published in the Pubmed electronic database involving the themes microglia, HPA axis and depression were used to meet the objectives. Results: Exposition to stressful events is considered a common factor in the mechanisms proposed to explain the depressive disorder. Stress can activate microglial cells, important immune components of the central nervous system (CNS). Moreover, another system involved in the physiological response to stressors is the hypothalamic-pituitary-adrenal (HPA) axis, the main stress response system responsible for the production of the glucocorticoid hormone (GC). Also, mediators released after microglial activation can stimulate the HPA axis, inducing production of GC. Likewise, high levels of GCs are also capable of activating microglia, generating a vicious cycle. Conclusion: Immune and neuroendocrine systems seems to work in a coordinated manner and that their dysregulation may be involved in the pathophysiology of depression since neuroinflammation and hypercortisolism are often observed in this disorder. [ABSTRACT FROM AUTHOR]

The development of aquaculture is closely related to human life. Crustaceans play essential roles in aquaculture. However, the cultivation of crustaceans has been plagued by various diseases, causing substantial economic losses. At present, the occurrence of shrimp diseases is directly related to environmental stress and physiological dysfunction, and especially environmental stress has become an important factor inducing diseases. Therefore, how to regulate the immune defence of crustaceans under environmental stress has become the primary problem in the prevention and control of shrimp diseases. The neuroendocrine‐immune system plays a vital role in maintaining homeostasis and enhancing environmental adaptability. Besides, in the evolutionary sense, with the theory that the nervous system and the immune system have a common origin put forward, the research on the neuroendocrine‐immune system of invertebrates has gradually become a hot spot. This review describes the evolution and communication mechanism of the neuroendocrine system and immune system in vertebrates and invertebrates, summarizes the characteristics of the neuroendocrine system and immune system in crustaceans, and focuses on how environmental stress affects the regulation of the neuroendocrine system on the immune system in crustaceans, as well as the influence of these regulations on host immune defence. This review also introduced the immune regulation of crustacean intestines under environmental stress and the effect of pathogen stress on crustacean immunity, hoping to lay a theoretical foundation for the follow‐up study of crustacean stress resistance and provide theoretical guidance for the healthy aquaculture of crustaceans. [ABSTRACT FROM AUTHOR]

Animal models have been utilized to explore the mechanisms by which mood disorders develop. Ethologically based stress paradigms are used to induce behavioral responses consistent with those observed in humans suffering from anxiety and depression. While mood disorders are more often diagnosed in women, animal studies are more likely to be carried out in male rodents. However, understanding the mechanisms behind anxiety- and depressive-like behaviors in both sexes is necessary to increase the predictive and construct validity of the models and identify therapeutic targets. To understand sex differences following stress, we must consider how all cell types within the central nervous system are influenced by the neuroendocrine system. This review article discusses the effects of stress and sex steroids on the macroglia: astrocytes and oligodendrocytes. Glia are involved in shaping the synapse through the regulation of neurotransmitter levels and energy resources, making them essential contributors to neural dynamics following stress. As the role of glia in neuromodulation has become more apparent, studies exploring the mechanisms by which glia are altered by stress and steroids will provide insight into sex differences in animal models. These insights will facilitate the optimization of animal models of psychiatric disorders and development of future therapeutic targets. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a class of neurodevelopmental disorders that affects males more frequently than females. Numerous genetic and environmental risk factors have been suggested to contribute to the development of ASD. However, no one factor can adequately explain either the frequency of the disorder or the male bias in its prevalence. Gonadal, thyroid, and glucocorticoid hormones all contribute to normal development of the brain, hence perturbations in either their patterns of secretion or their actions may constitute risk factors for ASD. Environmental factors may contribute to ASD etiology by influencing the development of neuroendocrine and neuroimmune systems during early life. Emerging evidence suggests that the placenta may be particularly important as a mediator of the actions of environmental and endocrine risk factors on the developing brain, with the male being particularly sensitive to these effects. Understanding how various risk factors integrate to influence neural development may facilitate a clearer understanding of the etiology of ASD. [ABSTRACT FROM AUTHOR]

Stress is well-known to contribute to the development of many psychiatric illnesses including alcohol and substance use disorder (AUD and SUD). The deleterious effects of stress have also been implicated in the acceleration of biological age, and age-related neurodegenerative disease. The physio-pathology of stress is regulated by the corticotropin-releasing factor (CRF) system, the upstream component of the hypothalamic-pituitary-adrenal (HPA) axis. Extensive literature has shown that dysregulation of the CRF neuroendocrine system contributes to escalation of alcohol consumption and, similarly, chronic alcohol consumption contributes to disruption of the stress system. The CRF system also represents the central switchboard for regulating homeostasis, and more recent studies have found that stress and aberrations in the CRF pathway are implicated in accelerated aging and age-related neurodegenerative disease. Corticotropin releasing factor binding protein (CRFBP) is a secreted glycoprotein distributed in peripheral tissues and in specific brain regions. It neutralizes the effects of CRF by sequestering free CRF, but may also possess excitatory function by interacting with CRF receptors. CRFBP's dual role in influencing CRF bioavailability and CRF receptor signaling has been shown to have a major part in the HPA axis response. Therefore, CRFBP may represent a valuable target to treat stress-related illness, including: development of novel medications to treat AUD and restore homeostasis in the aging brain. This narrative review focuses on molecular mechanisms related to the role of CRFBP in the progression of addictive and psychiatric disorders, biological aging, and age-related neurodegenerative disease. We provide an overview of recent studies investigating modulation of this pathway as a potential therapeutic target for AUD and age-related neurodegenerative disease. [ABSTRACT FROM AUTHOR]

This study was aimed to assess the neuroendocrine response to stress induced by different sports environments (a regular training session and a competitive event), to define the contribution of psychological and physical stress, and to check the possible relationship between state-anxiety and stress hormones responses to competitive and non-competitive sports practices. Twelve young national-level male swimmers participated in this investigation. Endorphins, adrenocorticotropin, and prolactin plasma levels were measured at baseline conditions (t0), before a regular swimming training session (t1), and before and after real swimming competition consisting of 100 m freestyle (t2 and t3, respectively). Moreover, state-anxiety was evaluated in all assessment time-points. The results showed no differences in endorphin, adrenocorticotropin, prolactin and state-anxiety between t0 and t1; however, significant increases in endorphins (142%), prolactin (137%) and state-anxiety (13%) were observed in t2. Huge stress response was observed in t3 (increases of 354%, 387%, and 250% for endorphins, adrenocorticotropin, and prolactin, respectively) although state-anxiety decreased slightly. Lastly, a lack of the relationship between stress hormones and state-anxiety was found in all conditions. Mental and especially physical stress associated with sports competition induces a significant release of stress hormones which is not relevant for the regular training session. [ABSTRACT FROM AUTHOR]

Heterogeneity among individual patients presents a fundamental challenge to effective treatment, since a treatment protocol working for a portion of the population often fails in others. We hypothesize that a computational pipeline integrating mathematical modeling and machine learning could be used to address this fundamental challenge and facilitate the optimization of individualized treatment protocols. We tested our hypothesis with the neuroendocrine systems controlled by the hypothalamic–pituitary–adrenal (HPA) axis. With a synergistic combination of mathematical modeling and machine learning (ML), this integrated computational pipeline could indeed efficiently reveal optimal treatment targets that significantly contribute to the effective treatment of heterogeneous individuals. What is more, the integrated pipeline also suggested quantitative information on how these key targets should be perturbed. Based on such ML revealed hints, mathematical modeling could be used to rationally design novel protocols and test their performances. We believe that this integrated computational pipeline, properly applied in combination with other computational, experimental and clinical research tools, can be used to design novel and improved treatment against a broad range of complex diseases. [ABSTRACT FROM AUTHOR]

Stress and its sequelae are very common in adults with autism spectrum disorder (ASD) without an intellectual disability (ID). Animal-assisted therapy (AAT) has shown physiological stress-reductive effects in children with ASD. The aim of the current study was to examine the acute psychophysiological response to an AAT session, and to examine the longer-term stress-physiological effects of the intervention, up until 10 weeks post-treatment, in comparison to waiting-list controls. A randomized controlled trial with pre-intervention (T0), post-intervention (T1: 10 weeks) and follow-up (T2: 20 weeks) measurements of neuroendocrine and cardiovascular measures, was conducted in 53 adults with ASD (N = 27 in intervention arm; N = 26 in control arm). Within the intervention group, stress-physiological data were collected during the 5th therapy session (acute effects). Data were analyzed with mixed models for outcome measures cortisol, alpha-amylase, heart rate variability and sympathetic activity. The AAT interventional session was significantly associated with reduced cortisol levels (β = −0.41, p =.010), while parasympathetic and sympathetic cardiovascular activity remained unaltered. No significant changes were found for stress-physiological measures at post-treatment time points. Acute stress reduction, reflected in significant reduction in cortisol levels, was found during an AAT session in adults with ASD, without ID. More research is needed to explore to what extent the specific factors of AAT have contributed to the decrease in cortisol and whether stress reduction is possible for the longer-term. [ABSTRACT FROM AUTHOR]

Long-term Antarctic expedition's studies indicated harmful or positive behavioral and psychophysiological adaptive changes that arise from adversities in isolated, confined, and extreme environments. Whereas most of the published studies focused on overwintering situations, most Brazilian Antarctic Program summer expeditions consist of short-term stays. We evaluated the influence of a permanence in Antarctic short-term (13-day) summer camp on the hormonal responses and mood states in eight volunteers. Data collection was carried out at the beginning (initial measure, days 3 to 5) and the end (final measurement, days 10 to 12) of the camping. Morning and evening samples of saliva were obtained to measure the testosterone and cortisol concentrations. Morning blood drops were used to determine thyroid-stimulating hormone (TSH) and thyroxine (T4) concentration. The volunteers also answered a mood states questionnaire. During the short-term camp, T4 (3.92 ± 0.75 vs 2.21 ± 0.71 µg.dL-1) and T4/TSH (3.16 ± 0.97 vs 1.79 ± 0.74 AU) reduced, without concomitant changes in TSH (1.28 ± 0.17 vs 1.30 ± 0.09 µU.mL-1), and salivary cortisol increased (2,392 ± 1,153 vs 4,440 ± 1,941 pg.mL-1) resulting in greater cortisol amplitude (calculated from the difference between morning and evening measurement, 1,400 ± 1,442 vs 3,230 ± 2,046). In men, testosterone in- creased as well (26.2 ± 12.5 vs 67.8 ± 45.8, all differences with P<0.05). There was a moderate effect in mood states evidenced by increased anger and fatigue, and reduced vigor. At the end of the camp, the change in cortisol correlated with anger, and the final cortisol values with anger and tension. We concluded that staying in a short-term summer camp in Antarctica induced endocrine and mood state changes, indicators of stress reaction. [ABSTRACT FROM AUTHOR]

Background: Microbial endocrinology, which is the study of neuroendocrine-based interkingdom signaling, provides a causal mechanistic framework for understanding the bi-directional crosstalk between the host and microbiome, especially as regards the effect of stress on health and disease. The importance of the cecal microbiome in avian health is well-recognized, yet little is understood regarding the mechanisms underpinning the avian host-microbiome relationship. Neuroendocrine plasticity of avian tissues that are focal points of host-microbiome interaction, such as the gut and lung, has likewise received limited attention. Avian in vivo models that enable the study of the neuroendocrine dynamic between host and microbiome are needed. As such, we utilized Japanese quail (Coturnix japonica) that diverge in corticosterone response to stress to examine the relationship between stress-related neurochemical concentrations at sites of host-microbe interaction, such as the gut, and the cecal microbiome. Results: Our results demonstrate that birds which contrast in corticosterone response to stress show profound separation in cecal microbial community structure as well as exhibit differences in tissue neurochemical concentrations and structural morphologies of the gut. Changes in neurochemicals known to be affected by the microbiome were also identified in tissues outside of the gut, suggesting a potential relationship in birds between the cecal microbiome and overall avian physiology. Conclusions: The present study provides the first evidence that the structure of the avian cecal microbial community is shaped by selection pressure on the bird for neuroendocrine response to stress. Identification of unique region-dependent neurochemical changes in the intestinal tract following stress highlights environmental stressors as potential drivers of microbial endocrinology-based mechanisms of avian host-microbiome dialogue. Together, these results demonstrate that tissue neurochemical concentrations in the avian gut may be related to the cecal microbiome and reveal the Japanese quail as a novel avian model in which to further examine the mechanisms underpinning these relationships. 1PBow1Pib_jvd7oFzE8EAD Video abstract [ABSTRACT FROM AUTHOR]

Copyright of Revista Chilena de Antropologia is the property of Universidad de Chile and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Stress is an inevitable part of life. Chronic stress on account of reasons like adversity, depression, anxiety, or loneliness/social isolation can endanger human health. Recent studies have shown that chronic stress can induce tumorigenesis and promote cancer development. This review describes the latest progress of research on the molecular mechanisms by which chronic stress promotes cancer development. Primarily, chronic stress activates the classic neuroendocrine system [the hypothalamic-pituitary-adrenal (HPA) axis] and the sympathetic nervous system (SNS) and leads to a decline and dysfunction of the prefrontal cortex and the hippocampus under stress. Stress hormones produced during the activation of both the HPA axis and the SNS can promote tumorigenesis and cancer development through a variety of mechanisms. Chronic stress can also cause corresponding changes in the body's immune function and inflammatory response, which is significant because a long-term inflammatory response and the decline of the body's immune surveillance capabilities are implicated in tumorigenesis. Stress management is essential for both healthy people and cancer patients. Whether drugs that limit the signaling pathways downstream of the HPA axis or the SNS can suppress chronic stress-induced cancers or prolong patient survival deserves further study. [ABSTRACT FROM AUTHOR]

Background: Chronic alcohol use results in changes to stress biology and autonomic arousal contributing to acute alcohol withdrawal symptoms, neuroendocrine tolerance of the hypothalamic–pituitary–adrenal axis responses, high stress‐induced craving, and risk of alcohol relapse. Thus, stress coping and recovery from alcohol during early abstinence may be jeopardized by such stress system dysfunction. Significant preclinical evidence suggests that noradrenergic disruption may contribute to these alcohol‐related stress arousal changes and that alpha‐1 adrenergic antagonists, such as prazosin, may normalize these stress system adaptations and reduce alcohol intake. Thus, we hypothesized that prazosin would reduce stress‐induced craving and improve neuroendocrine and autonomic response to stress and alcohol cue exposure during early abstinence. We secondarily also assessed the role of lifetime anxiety disorders on these prazosin effects. Methods: Forty inpatient treatment‐seeking alcohol‐dependent individuals were randomly assigned to receive placebo (n = 18) or 16 mg/d, T.I.D., prazosin (n = 22) in a double‐blind manner, titrated over 2 weeks. In weeks 3 to 4 after achieving full dose, patients were exposed to 3 5‐minute personalized guided imagery conditions (stress cue, alcohol cue, neutral/relaxing cue), on 3 consecutive days in a random, counterbalanced order. Alcohol craving, anxiety, heart rate, cortisol, and adrenocorticotropic hormone (ACTH) levels were assessed at baseline, following imagery and at repeated recovery timepoints. Results: Prazosin reduced stress cue–induced alcohol craving (p < 0.05) and stress‐ and alcohol cue–induced anxiety (p < 0.05) and increased heart rate responses in all imagery conditions (p < 0.05). Prazosin lowered basal cortisol and ACTH (p's < 0.05) and attenuated stress cue–induced rises in cortisol (p < 0.05) versus placebo. Finally, in those without lifetime anxiety disorder, the placebo group showed stress‐ and alcohol cue–induced increases in cortisol (p's < 0.05), while the prazosin group did not. Conclusions: Prazosin may attenuate stress cue–induced alcohol craving and anxiety during early abstinence while improving adrenergic and stress system function, effects which are independent of a history of lifetime anxiety disorders. [ABSTRACT FROM AUTHOR]

• Several stress-mediated pathways relevant to the formation of brain metastases have been identified. • Stress-induced activation of the neuroendocrine system, noradrenergic pathways and β-adrenergic signaling contribute to inflammation, impaired cellular immune response, and tumor angiogenesis. • Pharmacological blockade of stress- and inflammatory pathways, and immune stimulation, may provide a viable pharmacological strategy for suppressing many of the pathways through which the SNS can stimulate tumor progression and the formation of brain metastasis. Chronic stress can promote tumor growth and progression through immunosuppressive effects and bi-directional interactions between tumor cells and their microenvironment. β-Adrenergic receptor signaling plays a critical role in mediating stress-related effects on tumor progression. Stress-related mechanisms that modulate the dissemination of tumor cells to the brain have received scant attention. Brain metastases are highly resistant to chemotherapy and contribute considerably to morbidity and mortality in various cancers, occurring in up to 20% of patients in some cancer types. Understanding the mechanisms promoting brain metastasis could help to identify interventions that improve disease outcomes. In this review, we discuss biobehavioral, sympathetic, neuroendocrine, and immunological mechanisms by which chronic stress can impact tumor progression and metastatic dissemination to the brain. The critical role of the inflammatory tumor microenvironment in tumor progression and metastatic dissemination to the brain, and its association with stress pathways are delineated. We also discuss translational implications for biobehavioral and pharmacological interventions. [ABSTRACT FROM AUTHOR]

The present study was designed to assess the stress responses to a simulation model of the undersea environment that is similar to some undersea working conditions such as submarine rescue, underwater salvage and underwater construction. Restraint, hyperbaric air and immersion were chosen to produce the simulation stress model in rats for four hours. Rats were randomized into five groups: control group, restraint (R) group, hyperbaric air (H) group, restraint plus hyperbaric air (RH) group, and restraint plus hyperbaric air plus immersion (RHI) group. The results showed that the responses to the simulation stress model of the undersea environment induced by R, H, RH and RHI involved the upregulated norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) of the central nervous system (CNS), upregulated adrenocorticotropic hormone (ACTH), corticosterone (CORT) and blood glucose of the neuroendocrine system, upregulated interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) of the immune system, and increased anxiety in rats. Compared with hyperbaric air, restraint tended to activate stronger stress responses. Conclusively, this work established a simulation stress model of the undersea environment induced by restraint, hyperbaric air and immersion. It further provided experimental data of such a model that showed significant activation of the CNS, neuroendocrine and immune systems and anxiety in rats. In this experiment we provided an experimental basis for undersea work such as working aboard a submarine. [ABSTRACT FROM AUTHOR]

Mercury is a global pollutant and potent neurotoxic metal. Its most toxic and bioavailable form, methylmercury, can have both lethal and sublethal effects on wildlife. In birds, methylmercury exposure can disrupt behavior, hormones, the neuroendocrine system, and feather integrity. Lipid-rich tissues and secretions may be particularly susceptible to disruption by lipophilic contaminants such as methylmercury. One such substance is feather preen oil, a waxy secretion of the uropygial gland that serves multiple functions including feather maintenance, anti-parasitic defense, and chemical signaling. If methylmercury exposure alters preen oil composition, it could have cascading effects on feather quality, susceptibility to ectoparasites, and mate choice and other social behaviors. We investigated whether exposure to methylmercury, either alone or in association with other stressors, affects preen oil chemical composition. We used a two-factor design to expose adult song sparrows (Melospiza melodia) to an environmentally relevant dietary dose of methylmercury and/or to another stressor (unpredictable food supply) for eight weeks. The wax ester composition of preen oil changed significantly over the 8-week experimental period. This change was more pronounced in the unpredictable food treatment, regardless of dietary methylmercury. Contrary to our prediction, we found no main effect of methylmercury exposure on preen oil composition, nor did methylmercury interact with unpredictable food supply in predicting the magnitude of chemical shifts in preen oil. While it remains critical to study sublethal effects of methylmercury on wildlife, our findings suggest that the wax ester composition of preen oil is robust to environmentally relevant doses of this contaminant. [ABSTRACT FROM AUTHOR]

According to the hopelessness theory of depression, some individuals have a cognitive vulnerability (i.e., negative cognitive style) that interacts with stressful life events to produce depression. A negative cognitive style is associated with a maladaptive cognitive response to stress (i.e., increased negative attributions); however, no study has assessed whether this cognitive vulnerability is also associated with a maladaptive endocrine (e.g., cortisol) response to stress. If shown to be related, individual differences in cognitive style may potentially explain why the literature on the association between cortisol stress reactivity and depression is mixed, as cortisol responses to stress may vary as a function of attributional style. The aim of the present study was to provide a preliminary test of whether cognitive vulnerability was related to cortisol reactivity to an acute laboratory stressor among a sample of young adults (n = 20; Mage = 23.1 years; 10 females). Negative cognitive style and depressive symptoms were assessed via the Cognitive Style Questionnaire and the Patient Health Questionnaire, respectively. All participants also completed the Trier Social Stress Test (TSST). Salivary cortisol was collected before, during, and after the TSST. Results showed a significant association between negative cognitive style and cortisol stress reactivity, such that a greater negative cognitive style was related to a larger cortisol response to the TSST. Post hoc analyses revealed that this association was moderated by gender (i.e., effect observed in males only). Cortisol responses to the TSST, in general, were lower among females, but this relationship was not moderated by cognitive style. These findings may be related to underlying gender differences in stress vulnerability, which may have clinical implications for understanding the interactive effect of cognitive and neuroendocrine processes on vulnerability and resiliency to depression. [ABSTRACT FROM AUTHOR]

Copyright of Voces de la Educacion is the property of Voces de la Educacion and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

A class of glial cell, astrocytes, is highly abundant in the central nervous system (CNS). In addition to maintaining tissue homeostasis, astrocytes regulate neuronal communication and synaptic plasticity. There is an ever‐increasing appreciation that astrocytes are involved in the regulation of physiology and behaviour in normal and pathological states, including within neuroendocrine systems. Indeed, astrocytes are direct targets of hormone action in the CNS, via receptors expressed on their surface, and are also a source of regulatory neuropeptides, neurotransmitters and gliotransmitters. Furthermore, as part of the neurovascular unit, astrocytes can regulate hormone entry into the CNS. This review is intended to provide an overview of how astrocytes are impacted by and contribute to the regulation of a diverse range of neuroendocrine systems: energy homeostasis and metabolism, reproduction, fluid homeostasis, the stress response and circadian rhythms. [ABSTRACT FROM AUTHOR]

Early-life stressful experiences are critical for plasticity and development, shaping adult neuroendocrine response and future health. Stress response is mediated by the autonomous nervous system and the hypothalamic–pituitary–adrenal (HPA) axis while various environmental stimuli are encoded via epigenetic marks. The stress response system maintains homeostasis by regulating adaptation to the environmental changes. Pre-conceptual and in utero stressors form the fetal epigenetic profile together with the individual genetic profile, providing the background for individual stress response, vulnerability, or resilience. Postnatal and adult stressful experiences may act as the definitive switch. This review addresses the issue of how preconceptual in utero and postnatal events, together with individual differences, shape future stress responses. Putative markers of early-life adverse effects such as prematurity and low birth weight are emphasized, and the epigenetic, mitochondrial, and genomic architecture regulation of such events are discussed. [ABSTRACT FROM AUTHOR]

Converging evidence across species highlights the contribution of environmental stress to anhedonia (loss of pleasure and/or motivation). However, despite a clear link between stress and the emergence of anhedonic-like behavior in both human and animal models, the underlying biological pathways remain elusive. Here, we synthesize recent findings across multiple levels, from molecular signaling pathways through whole-brain networks, to discuss mechanisms through which stress may influence anhedonia. Recent work suggests the involvement of diverse systems that converge on the mesolimbic reward pathway, including medial-prefrontal cortical circuitry, neuroendocrine stress responses, homeostatic energy regulation systems, and inflammation. We conclude by emphasizing the need to disentangle the influences of key dimensions of stress on specific aspects of reward processing, taking into account individual differences that could moderate this relationship. Highlights Converging evidence across species suggests that environmental stressors contribute to the development of anhedonia (i.e., decreased motivation/responsiveness to reward), in part through alterations in the mesolimbic dopamine system. At the circuit level, stress may disrupt mesolimbic reward functioning through a number of possible mechanisms: alternations in the input from medial prefrontal cortex; the actions of CRF secreted by neuroendocrine stress systems; or signals from homeostatic energy systems, including GLP-1 neurons. At the molecular signaling level, inflammation in response to stress could disrupt mesolimbic reward functioning by interfering with dopamine synthesis, or via kynurenine-induced oxidative stress. A thorough conceptualization of the relationship between stress and anhedonia should depict how different types of stress cause changes in molecular signaling and neural circuits, leading to specific alterations in motivation and reward processing. [ABSTRACT FROM AUTHOR]

In this review, the effects of stress on alcohol drinking are discussed. The interactions between biological stress systems and alcohol drinking are examined, with a focus on the hypothalamic pituitary adrenal axis, corticotropin releasing factor, dynorphin, neuropeptide Y, and norepinephrine systems. Findings from animal models suggest that these biological stress systems may be useful targets for medications development for alcohol use disorder and co-occurring stress-related disorders in humans. [ABSTRACT FROM AUTHOR]

Highlights • There was a non-linear association between discrimination and allostatic load. • The association between discrimination and allostatic load varied by education. • A U-shaped relationship emerged among those with lower education. • High discrimination had a buffering effect among those with higher education. • Associations were found for allostatic load and in system-specific analyses. Abstract Objective To examine the association between self-reported racial discrimination and allostatic load, and whether the association differs by socioeconomic position. Methods We recruited a purposive cross-section of midlife (ages 30–50) African American women residing in four San Francisco Bay area counties (n = 208). Racial discrimination was measured using the Experience of Discrimination scale. Allostatic load was measured as a composite of 15 biomarkers assessing cardiometabolic, neuroendocrine, and inflammatory activity. We calculated four composite measures of allostatic load and three system-specific measures of biological dysregulation. Multivariable regression was used to examine associations, while adjusting for relevant confounders. Results In the high education group, reporting low (b = −1.09, P =.02, 95% CI = −1.99, −0.18) and very high (b = −1.88, P =.003, 95% CI = −3.11, −0.65) discrimination was associated with lower allostatic load (reference=moderate). Among those with lower education, reporting low (b = 2.05, P =.008, 95% CI = 0.55,3.56) discrimination was associated with higher allostatic load. Similar but less consistent associations were found for poverty status. Associations were similar for cardiometabolic functioning, but not for neuroendocrine or inflammatory activity. Conclusions Racial discrimination may be an important predictor of cumulative physiologic dysregulation. Factors associated with educational attainment may mitigate this association for African American women and other groups experiencing chronic social stress. [ABSTRACT FROM AUTHOR]

Highlights • UC patients in remission (UCR) exhibit higher levels of anxiety, depression, and perceived stress than healthy controls. • Immune cells from UCR have diminished capacity to produce IL-10 in response to endotoxin. • Adrenergic upregulation of IL-10 production is impaired in UCR. • Downregulation of TNF-α by glucocorticoid, adrenergic, and cholinergic agonists is as efficient as in healthy individuals. • UCR patients exhibit signs of systemic low-grade inflammation. Abstract Stress demonstrably contributes to disease course in patients with inflammatory bowel diseases but the underlying mechanisms remain elusive. Here, we investigated if neuroendocrine regulation of pro- and anti-inflammatory cytokine production by peripheral blood immune cells is altered in patients with ulcerative colitis in remission (UCR). Using a whole blood stimulation assay, we measured the sensitivity of lipopolysaccharide (LPS)-induced TNF-α and IL-10 production to the glucocorticoid receptor agonist dexamethasone (DEX), the β 2 -adrenergic receptor agonist terbutaline (TERB), and the α7-nicotinic acetylcholine receptor agonist 3-[2,4-dimethoxy-benzylidene]-anabaseine (GTS-21) in UCR patients (N = 26) and in healthy controls (HC, N = 25). Additionally, we assessed anxiety and depression symptoms as well as chronic perceived stress and disease-specific quality of life. Results showed that UCR patients exhibited greater anxiety, depression and chronic stress levels than HC, and reduced disease-specific quality of life. Plasma concentrations of TNF-α, IL-8, C-reactive protein (CRP) and lipopolysaccharide binding protein (LBP) were significantly higher, while LPS-induced IL-10 production was substantially lower in UCR compared to HC. Independent of group, DEX and GTS-21 dose-dependently inhibited TNF-α and IL-10 production, whereas TERB inhibited TNF-α and upregulated IL-10 production. However, at higher TERB doses (i.e., stress levels), upregulation of IL-10 production was significantly diminished in UCR compared to HC. Together, these findings demonstrate that downregulation of pro-inflammatory cytokine production in peripheral blood immune cells through glucocorticoid, adrenergic, and cholinergic mechanisms is essentially normal in UC in clinical remission and as efficient as in healthy individuals. However, UCR patients exhibited signs of systemic low-grade inflammation and dysregulation of anti-inflammatory IL-10 production. Impaired adrenergic upregulation of IL-10 production during remission could be one mechanism how stress facilitates relapse and conversion to symptomatic disease in these patients. [ABSTRACT FROM AUTHOR]

Restraint stress is a psychosocial stressor that suppresses reproductive status, including LH pulsatile secretion, but the neuroendocrine mechanisms underlying this inhibition remains unclear. Reproductive neural populations upstream of gonadotropin-releasing hormone (GnRH) neurons, such as kisspeptin, neurokinin B and RFRP-3 (GnIH) neurons, are possible targets for psychosocial stress to inhibit LH pulses, but this has not been well examined, especially in mice in which prior technical limitations prevented assessment of in vivo LH pulse secretion dynamics. Here, we examined whether one-time acute restraint stress alters in vivo LH pulsatility and reproductive neural populations in male mice, and what the time-course is for such alterations. We found that endogenous LH pulses in castrated male mice are robustly and rapidly suppressed by one-time, acute restraint stress, with suppression observed as quickly as 12-18 min. This rapid LH suppression parallels with increased in vivo corticosterone levels within 15 min of restraint stress. Although Kiss1, Tac2 and Rfrp gene expression in the hypothalamus did not significantly change after 90 or 180 min restraint stress, arcuate Kiss1 neural activation was significantly decreased after 180 min. Interestingly, hypothalamic Rfrp neuronal activation was strongly increased at early times after restraint stress initiation, but was attenuated to levels lower than controls by 180 min of restraint stress. Thus, the male neuroendocrine reproductive axis is quite sensitive to short-term stress exposure, with significantly decreased pulsatile LH secretion and increased hypothalamic Rfrp neuronal activation occurring rapidly, within minutes, and decreased Kiss1 neuronal activation also occurring after longer stress durations. [ABSTRACT FROM AUTHOR]

• The HPI-axis of tilapia facing salinity challenges was characterized. • Circulating cortisol was generally unaffected by salinity challenges. • Pituitary pomc expression was higher in fish in SW compared with those in FW. • Branchial corticosteroid receptor expression decreased in FW in both transfer and tidal paradigms. In estuarine environments, euryhaline fish maintain a narrow range of internal osmolality despite daily changes in environmental salinity that can range from fresh water (FW) to seawater (SW). The capacity of euryhaline fish to maintain homeostasis in a range of environmental salinities is primarily facilitated by the neuroendocrine system. One such system, the hypothalamic-pituitary-interrenal (HPI) axis, culminates in the release of corticosteroids such as cortisol into circulation. Cortisol functions as both a mineralocorticoid and glucocorticoid in fish because of its roles in osmoregulation and metabolism, respectively. The gill, a key site for osmoregulation, and the liver, the primary storage site for glucose, are known targets of cortisol's actions during salinity stress. While cortisol facilitates acclimation to SW environments, less is known on its role during FW adaptation. In this study, we characterized the responses of plasma cortisol, mRNA expression of pituitary pro-opiomelanocortin (pomc), and mRNA expression of liver and gill corticosteroid receptors (gr1, gr2, and mr) in the euryhaline Mozambique tilapia (Oreochromis mossambicus) under salinity challenges. Specifically, tilapia were subjected to salinity transfer regimes from steady-state FW to SW, SW to FW (experiment 1) or steady state FW or SW to tidal regimen (TR, experiment 2). In experiment 1, fish were sampled at 0 h, 6 h, 1, 2, and 7 d post transfer; while in experiment 2, fish were sampled at day 0 and day 15. We found a rise in pituitary pomc expression and plasma cortisol following transfer to SW while branchial corticosteroid receptors were immediately downregulated after transfer to FW. Moreover, branchial expression of corticosteroid receptors changed with each salinity phase of the TR, suggesting rapid environmental modulation of corticosteorid action. Together, these results support the role of the HPI-axis in promoting salinity acclimation, including in dynamically-changing environments. [ABSTRACT FROM AUTHOR]

Macrophages carry out numerous physiological activities that are essential for both systemic and local homeostasis, as well as innate and adaptive immune responses. Their biology is intricately regulated by hormones, neuropeptides, and neurotransmitters, establishing distinct neuroendocrine axes. The control is pleiotropic, including maturation of bone marrow-derived myeloid precursors, cell differentiation into functional subpopulations, cytotoxic activity, phagocytosis, production of inflammatory mediators, antigen presentation, and activation of effector lymphocytes. Additionally, neuroendocrine components modulate macrophage ability to influence tumor growth and to prevent the spreading of infective agents. Interestingly, macrophage-derived factors enhance glucocorticoid production through the stimulation of the hypothalamic–pituitary–adrenal axis. These bidirectional effects highlight a tightly controlled balance between neuroendocrine stimuli and macrophage function in the development of innate and adaptive immune responses. Herein, we discuss how components of neuroendocrine axes impact on macrophage development and function and may ultimately influence inflammation, tissue repair, infection, or cancer progression. The knowledge of the crosstalk between macrophages and endocrine or brain-derived components may contribute to improve and create new approaches with clinical relevance in homeostatic or pathological conditions.