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This article is from Translational Psychiatry , volume 2 . Abstract Huntington's disease (HD) has long been regarded as a disease of the central nervous system, partly due to typical disease symptoms that include loss of motor control, cognitive deficits and neuropsychiatric disturbances. However, the huntingtin gene is ubiquitously expressed throughout the body. We had previously reported a female-specific depression-related behavioural phenotype in the R6/1 transgenic mouse model of HD. One hypothesis suggests that pathology of the hypothalamic-pituitary-adrenal (HPA) axis, the key physiological stress-response system that links central and peripheral organs, is a cause of depression. There is evidence of HPA axis pathology in HD, but whether it contributes to the female R6/1 behavioural phenotype is unclear. We have examined HPA axis response of R6/1 mice following acute stress and found evidence of a female-specific dysregulation of the HPA axis in R6/1 mice, which we further isolated to a hyper-response of adrenal cortical cells to stimulation by adrenocorticotrophin hormone. Interestingly, the adrenal pathophysiology was not detected in mice that had been housed in environmentally enriching conditions, an effect of enrichment that was also reproduced in vitro. This constitutes the first evidence that environmental enrichment can in fact exert a lasting influence on peripheral organ function. Cognitive stimulation may therefore not only have benefits for mental function, but also for overall physiological wellbeing.

This article is from The Journal of Endocrinology , volume 221 . Abstract Obesity is a risk factor for sepsis morbidity and mortality, whereas the hypothalamic–pituitary–adrenal (HPA) axis plays a protective role in the body's defence against sepsis. Sepsis induces a profound systemic immune response and cytokines serve as excellent markers for sepsis as they act as mediators of the immune response. Evidence suggests that the adipokine leptin may play a pathogenic role in sepsis. Mouse endotoxaemic models present with elevated leptin levels and exogenously added leptin increased mortality whereas human septic patients have elevated circulating levels of the soluble leptin receptor (Ob-Re). Evidence suggests that leptin can inhibit the regulation of the HPA axis. Thus, leptin may suppress the HPA axis, impairing its protective role in sepsis. We hypothesised that leptin would attenuate the HPA axis response to sepsis. We investigated the direct effects of an i.p. injection of 2 mg/kg leptin on the HPA axis response to intraperitoneally injected 25 μg/kg lipopolysaccharide (LPS) in the male Wistar rat. We found that LPS potently activated the HPA axis, as shown by significantly increased plasma stress hormones, ACTH and corticosterone, and increased plasma interleukin 1β (IL1β) levels, 2 h after administration. Pre-treatment with leptin, 2 h before LPS administration, did not influence the HPA axis response to LPS. In turn, LPS did not affect plasma leptin levels. Our findings suggest that leptin does not influence HPA function or IL1β secretion in a rat model of LPS-induced sepsis, and thus that leptin is unlikely to be involved in the acute-phase endocrine response to bacterial infection in rats.

This article is from Theoretical Biology & Medical Modelling , volume 10 . Abstract Major depressive disorder (MDD) is a multifactorial disorder known to be influenced by both genetic and environmental factors. MDD presents a heritability of 37%, and a genetic contribution has also been observed in studies of family members of individuals with MDD that imply that the probability of suffering the disorder is approximately three times higher if a first-degree family member is affected. Childhood maltreatment and stressful life events (SLEs) have been established as critical environmental factors that profoundly influence the onset of MDD. The serotonin pathway has been a strong candidate for genetic studies, but it only explains a small proportion of the heritability of the disorder, which implies the involvement of other pathways. The serotonin (5-HT) pathway interacts with the stress response pathway in a manner mediated by the hypothalamic-pituitary-adrenal (HPA) axis. To analyze the interaction between the pathways, we propose the use of a synchronous Boolean network (SBN) approximation. The principal aim of this work was to model the interaction between these pathways, taking into consideration the presence of selective serotonin reuptake inhibitors (SSRIs), in order to observe how the pathways interact and to examine if the system is stable. Additionally, we wanted to study which genes or metabolites have the greatest impact on model stability when knocked out in silico. We observed that the biological model generated predicts steady states (attractors) for each of the different runs performed, thereby proving that the system is stable. These attractors changed in shape, especially when anti-depressive drugs were also included in the simulation. This work also predicted that the genes with the greatest impact on model stability were those involved in the neurotrophin pathway, such as CREB, BDNF (which has been associated with major depressive disorder in a variety of studies) and TRkB, followed by genes and metabolites related to 5-HT synthesis.

This article is from PLoS ONE , volume 9 . Abstract Background: The hypothalamic-pituitary-adrenal (HPA) axis regulates stress responses and HPA dysfunction has been associated with several chronic diseases. Low birthweight may be associated with HPA dysfunction in later life, yet human studies are inconclusive. The primary study aim was to identify genetic variants associated with HPA axis function. A secondary aim was to evaluate if these variants modify the association between birthweight and HPA axis function in adolescents. Methods: Morning fasted blood samples were collected from children of the Western Australia Pregnancy Cohort (Raine) at age 17 (n = 1077). Basal HPA axis function was assessed by total cortisol, corticosteroid binding globulin (CBG), and adrenocorticotropic hormone (ACTH). The associations between 124 tag single nucleotide polymorphisms (SNPs) within 16 HPA pathway candidate genes and each hormone were evaluated using multivariate linear regression and penalized linear regression analysis using the HyperLasso method. Results: The penalized regression analysis revealed one candidate gene SNP, rs11621961 in the CBG encoding gene (SERPINA6), significantly associated with total cortisol and CBG. No other candidate gene SNPs were significant after applying the penalty or adjusting for multiple comparisons; however, several SNPs approached significance. For example, rs907621 (p = 0.002) and rs3846326 (p = 0.003) in the mineralocorticoid receptor gene (NR3C2) were associated with ACTH and SERPINA6 SNPs rs941601 (p = 0.004) and rs11622665 (p = 0.008), were associated with CBG. To further investigate our findings for SERPINA6, rare and common SNPs in the gene were imputed from the 1,000 genomes data and 8 SNPs across the gene were significantly associated with CBG levels after adjustment for multiple comparisons. Birthweight was not associated with any HPA outcome, and none of the gene-birthweight interactions were significant after adjustment for multiple comparisons. Conclusions: Our study suggests that genetic variation in the SERPINA6 gene may be associated with altered CBG levels during adolescence. Replication of these findings is required.

This paper generalizes the existing minimal model of the hypothalamic-pituitary-adrenal (HPA) axis in a realistic way, by including memory terms: distributed time delays, on one hand and fractional-order derivatives, on the other hand. The existence of a unique equilibrium point of the mathematical models is proved and a local stability analysis is undertaken for the system with general distributed delays. A thorough bifurcation analysis for the distributed delay model with several types of delay kernels is provided. Numerical simulations are carried out for the distributed delays models and for the fractional-order model with discrete delays, which substantiate the theoretical findings. It is shown that these models are able to capture the vital mechanisms of the HPA system.

This scoping review will analyze the state of the literature regarding whether or not people living with HIV experience abnormally high or low cortisol levels and if this is associated with mental and physical health conditions. Our research questions are: 1) What methods are commonly used to assess cortisol levels in people living with HIV? 2) Do elevated/suppressed cortisol levels contribute to mental and physical health outcomes in people living with HIV. 3) Are their sex/gender differences in these relationships?

This scoping review will analyze the state of the literature regarding whether or not people living with HIV experience abnormally high or low cortisol levels and if this is associated with mental and physical health conditions. Our research questions are: 1) What methods are commonly used to assess cortisol levels in people living with HIV? 2) Do elevated/suppressed cortisol levels contribute to mental and physical health outcomes in people living with HIV. 3) Are their sex/gender differences in these relationships?

This article is from The Journal of Experimental Medicine , volume 208 . Abstract Systemic and CNS-delimited inflammation triggers skeletal muscle catabolism in a manner dependent on glucocorticoid signaling.

This article is from The Journal of Experimental Medicine , volume 208 . Abstract Systemic and CNS-delimited inflammation triggers skeletal muscle catabolism in a manner dependent on glucocorticoid signaling.

This article is from Frontiers in Cellular Neuroscience , volume 6 . Abstract Dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis has been implicated in a range of affective and stress-related disorders. The regulatory systems that control HPA activity are subject to modulation by environmental influences, and stressful life events or circumstances can promote subsequent HPA dysregulation. The brain is a major regulator of the HPA axis, and stress-induced plasticity of the neural circuitry involved in HPA regulation might constitute an etiological link between stress and the development of HPA dysregulation. This review focuses on the synaptic regulation of neuroendocrine corticotropin-releasing hormone (CRH) neurons of the hypothalamic paraventricular nucleus, which are the cells through which the brain predominantly exerts its influence on the HPA axis. CRH neuronal activity is largely orchestrated by three neurotransmitters: GABA, glutamate, and norepinephrine. We discuss our current understanding of the neural circuitry through which these neurotransmitters regulate CRH cell activity, as well as the plastic changes in this circuitry induced by acute and chronic stress and the resultant changes in HPA function.

This article is from Frontiers in Cellular Neuroscience , volume 6 . Abstract Dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis has been implicated in a range of affective and stress-related disorders. The regulatory systems that control HPA activity are subject to modulation by environmental influences, and stressful life events or circumstances can promote subsequent HPA dysregulation. The brain is a major regulator of the HPA axis, and stress-induced plasticity of the neural circuitry involved in HPA regulation might constitute an etiological link between stress and the development of HPA dysregulation. This review focuses on the synaptic regulation of neuroendocrine corticotropin-releasing hormone (CRH) neurons of the hypothalamic paraventricular nucleus, which are the cells through which the brain predominantly exerts its influence on the HPA axis. CRH neuronal activity is largely orchestrated by three neurotransmitters: GABA, glutamate, and norepinephrine. We discuss our current understanding of the neural circuitry through which these neurotransmitters regulate CRH cell activity, as well as the plastic changes in this circuitry induced by acute and chronic stress and the resultant changes in HPA function.

This article is from Advances in Dermatology and Allergology/Postȩpy Dermatologii i Alergologii , volume 31 . Abstract Introduction: Treatment of difficult asthma with oral corticosteroids (OCS) may suppress the hypothalamic-pituitary-adrenal axis. Aim: In this study we have checked if the substitution of OCS with very high doses of ciclesonide may restore the adrenal function without losing the control of the disease. Material and methods: In 5 patients with difficult, uncontrolled asthma despite treatment with OCS, inhaled and systemic glucocorticosteroids were replaced with very high doses of ciclesonide (1600–2400 µg/day). The symptoms of asthma and the lung function were assessed at baseline and on the 28th, 56th and 70th day of treatment, whereas the levels of cortisol and adrenocorticotropic hormone (ACTH) in the morning were measured at baseline and on the 28th and the 56th day of treatment. Results: In all patients, the control of asthma symptoms, measured with Asthma Control Test questionnaire, improved from the mean score of 9.4 to 19.8 in 70 days. In 4 subjects force expiratory volume in 1 s improved gradually through the entire study reaching a mean improvement of 585 ml in 70 days. The ACTH levels were normalized in 3 patients after 28 days of observation and in all patients after 56 days. The cortisol level was normalized in 4 patients after 28 days and in another subject after 56 days of treatment with ciclesonide. Conclusions: Switching from prednisone to very high doses of ciclesonide normalized the hypothalamic-pituitary adrenal axis function and also improved the disease control and the lung function in these 5 patients with difficult asthma.

This article is from Physiological Reports , volume 2 . Abstract Chronic calorie restriction (CR) is one of the few interventions to improve longevity and quality of life in a variety of species. It also reduces behavioral indices of anxiety and influences some stress hormones under basal conditions. However, it is not known how CR influences hypothalamic–pituitary–adrenal (HPA) axis function or if those on a CR diet have heightened HPA axis responses to stress. We hypothesized elevated basal glucocorticoid levels induced by CR would lead to exacerbated HPA axis responses to the psychological stress, restraint, in the male rat. We first confirmed rats fed 75% of their normal calorie intake for 3 weeks were less anxious than ad libitum‐fed (AD) rats in the elevated plus maze test for anxiety. The anxiolytic effect was mild, with only grooming significantly attenuated in the open field and no measured behavior affected in the light/dark box. Despite elevated basal glucocorticoids, CR rats had very similar hormonal and central responses to 15‐min restraint to the AD rats. Both CR and AD rats responded to restraint stress with a robust increase in glucocorticoids that was resolved by 60 min. Both groups also showed robust neuronal activation in the paraventricular nucleus of the hypothalamus and in other stress‐ and feeding‐sensitive brain regions that was not substantially affected by calorie intake. Our findings thus demonstrate chronic mild CR is subtly anxiolytic and is not likely to affect HPA axis responses to psychological stress. These findings support research suggesting a beneficial effect of mild CR.

This article is from Dialogues in Clinical Neuroscience , volume 8 . Abstract Animals respond to stress by activating a wide array of behavioral and physiological responses that are collectively referred to as the stress response. Corticotropin-releasing factor (CRF) plays a central role in the stress response by regulating the hypothalamic-pituitary-adrenal (HPA) axis. In response to stress, CRF initiates a cascade of events that culminate in the release of glucocorticoids from the adrenal cortex. As a result of the great number of physiological and behavioral effects exerted by glucocorticoids, several mechanisms have evolved to control HPA axis activation and integrate the stress response. Glucocorticoid feedback inhibition plays a prominent role in regulating the magnitude and duration of glucocorticoid release. In addition to glucocorticoid feedback, the HPA axis is regulated at the level of the hypothalamus by a diverse group of afferent projections from limbic, mid-brain, and brain stem nuclei. The stress response is also mediated in part by brain stem noradrenergic neurons, sympathetic andrenornedullary circuits, and parasympathetic systems. In summary, the aim of this review is to discuss the role of the HPA axis in the integration of adaptive responses to stress. We also identify and briefly describe the major neuronal and endocrine systems that contribute to the regulation of the HPA axis and the maintenance of homeostasis in the face of aversive stimuli.

This article is from Annals of Intensive Care , volume 1 . Abstract Background: Sepsis continues to be a poorly understood syndrome with a high mortality rate. While we are beginning to decipher the intricate interplay of the inflammatory response during sepsis, the precise regulation of the hypothalamic-pituitary-adrenal (HPA) axis and its impact on electrolyte homeostasis during sepsis remains incompletely understood. Methods: Sepsis was induced in adult male Sprague-Dawley rats by cecal ligation and puncture (CLP). Plasma samples were obtained as a function of time (6-48 hrs) after CLP and compared with healthy animals (neg ctrl). Samples were analyzed for adrenocorticotropin (ACTH), corticosterone, and aldosterone levels, as well as concentrations of sodium (Na+), potassium (K+), chloride (Cl-), and magnesium (Mg2+). Results: ACTH levels were found to be significantly reduced 6-24 hrs after CLP in comparison to baseline levels and displayed gradual recovery during the later course (24-48 hrs) of sepsis. Plasma corticosterone concentrations exhibited a bell-shaped response, peaking between 6 and 12 hrs followed by rapid decline and concentrations below negative control levels 48 hrs after injury. Aldosterone levels in septic animals were continuously elevated between 6 and 48 hrs. Whereas plasma Na+ levels were found to be persistently elevated following CLP, levels of K+, Cl- and Mg2+ were significantly reduced as a function of time and gradually recovered during the later course of sepsis. Conclusions: CLP-induced sepsis resulted in dynamic changes of ACTH, corticosterone, and aldosterone levels. In addition, electrolyte levels showed significant disturbances after CLP. These electrolyte perturbations might be evoked by a downstream effect or a dysfunctional HPA-axis response during sepsis and contribute to severe complications during sepsis.

This article is from Annals of the New York Academy of Sciences , volume 1264 . Abstract Obesity, particularly the abdominal phenotype, has been ascribed to an individual maladaptation to chronic environmental stress exposure mediated by a dysregulation of related neuroendocrine axes. Alterations in the control and action of the hypothalamic–pituitary–adrenal axis play a major role in this context, with the participation of the sympathetic nervous system. The ability to adapt to chronic stress may differ according to sex, with specific pathophysiological events leading to the development of stress-related chronic diseases. This seems to be influenced by the regulatory effects of sex hormones, particularly androgens. Stress may also disrupt the control of feeding, with some differences according to sex. Finally, the amount of experimental data in both animals and humans may help to shed more light on specific phenotypes of obesity, strictly related to the chronic exposure to stress. This challenge may potentially imply a different pathophysiological perspective and, possibly, a specific treatment.

http://uf.catalog.fcla.edu/uf.jsp?st=UF029330358&ix=pm&I=0&V=D&pm=1

Amelia B. Edwards wrote this historical, egyptological, and cultural study in in 1877, and it became an immediate best-seller, reprinted in 1888 at home in England and abroad. She travelled throughout Egypt at a time when most women didn't leave home. One of the pioneering Egyptologists of the age, she established the Edwards Chair of Egyptology, occupied first by the great Sir William Matthew Flinders Petrie.<br /><br /> This book is in a sense a seminal work, known to have influenced the modern writings of Elizabeth Peters in her Amelia Peabody Emerson murder-mystery series. (Summary by Sibella Denton)

Amelia B. Edwards wrote this historical travelogue in in 1873. The book describes her travels through a relatively un-visited area in the South Tyrol district of Italy. The Dolomites are a part of that most famous of mountain chains, the Alps. In this book, the Writer and her friend and companion, L., travel from Southern Italy, having over-wintered there, to visit the Dolomite district. Her chatty style, dry sense of humor, accuracy of facts, and sympathy for humanity set her works apart. The slice of Victorian British life presented is quite captivating. <p> She would later travel throughout Europe and Egypt at a time when most women didn't leave home. Later she was to become one of the pioneering Egyptologists of the age. This is her first travelogue.

3Football Days: Memories of the Game and of the Men behind the Ball

By William Hanford Edwards

A book reminiscent of the days when football was gaining popularity in America. (summary by Ian Hatley)

Jonathan Edwards was a colonial American Congregational preacher, theologian, and missionary to Native Americans. Edwards "is widely acknowledged to be America's most important and original philosophical theologian." His work is very broad in scope, but he is often associated with his defense of Calvinist theology, the metaphysics of theological determinism, and the Puritan heritage. His famous sermon "Sinners in the Hands of an Angry God," emphasized the just wrath of God against sin and contrasted it with the provision of God for salvation; the intensity of his preaching sometimes resulted in members of the audience fainting, swooning, and other more obtrusive reactions. The swooning and other behaviors in his audience caught him up in a controversy over "bodily effects" of the Holy Spirit's presence. (Summary by Wikipedia)<br /><br />This collection contains nineteen of his sermons, including "Sinners in the Hands of an Angry God."

5Book of Old English Ballads

By George Wharton Edwards

In this selection... the aim has been to bring within moderate compass a collection of these songs of the people which should fairly represent the range, the descriptive felicity, the dramatic power, and the genuine poetic feeling of a body of verse which is still, it is to be feared, unfamiliar to a large number of those to whom it would bring refreshment and delight. (Summary from introduction)

6Old Coast Road From Boston to Plymouth

By Agnes Edwards

A delightful trip from Boston through a dozen South Shore towns to Plymouth, stopping in each to explore a bit of the local history and 'modern' highlights. Written in 1920, it's a great journey through the past. (Summary by Steve Mattern)

7Treasury of Heroes and Heroines

By Clayton Edwards

It would be pleasant indeed to gather the characters of this book together and listen to the conversation of wholly different but interested couples—for this is a book of contrasts and has been written as such. Lives of the most dramatic and adventurous quality have been gathered from all corners of the earth, and from every age in history, in such a way that they may cover the widest possible variety of human experience. <br><br> The publishers believe that such a book would not be complete without some characters that are no less real because they have lived only in the minds of men. No explanation is needed for semi-historical characters like King Arthur, Robin Hood and William Tell, while Don Quixote, the Prince of Madness, and Rip Van Winkle, the Prince of Laziness, have been included, not because they were essentially heroic in themselves (although Don Quixote might well have claimed the laurel) but because they became heroes in the opinion of others through the very qualities that brought about their downfall. As involuntary heroes, they furnish a pleasant contrast to the more serious, actual and transcendental figures of saints, martyrs, warriors, discoverers and statesmen with which these pages are filled; they enrich the "Treasury," widen its range of colors and perform the necessary function of court jesters in the Hall of Fame. (Summary From the Preface)

“Clearly he was one of those rare beings who can radiate energy standing still and convey the impression of impetuous force without motion, a trick of the eyes, a refusal to sag…. King saw her first as she started across Cherry Street from the far corner, a slender figure moving with grace and assurance through the dangerous procession of motor cars, still handled in the South as new toys,…” What is the secret that may keep these two, meant for each other, apart? (Book quote and David Wales)

Jonathan Edwards (1703-1758) was a pre-revolutionary American pastor and academic in Massachusetts, and is also widely considered to be both the last of the great Puritans, and a founder of modern evangelicalism. In 1732, his church and many churches in the surrounding region experienced “The Great Awakening”, a massive religious revival. The Great Awakening saw many people having heightened “affections”, or emotions, in response to their increased spirituality – this included excessive weeping, joyous outbursts, and many other manifestations that concerned more conservative people around them. Edwards wrote Religious Affections in order to show that affections could be a legitimate part of Christian spirituality, but only when conjoined with sound theology and godly practice. The book now stands as a classic in the field of Christian spirituality. (Summary by Matthew James Gray)

Disproportionately remembered as a hellfire-and-brimstone Puritan preacher on the basis of the excessively-anthologized "Sinners in the Hands of an Angry God," Jonathan Edwards was a noted philosopher in the field of Aesthetics, or the metaphysics of Beauty. An examination even of his sermons reveals constant references to this philosophical preoccupation, his favorite word in many passages seeming to be "Sweetness," by which term he intended to convey a rich sense of Beauty. In "A Dissertation Concerning the Nature of True Virtue," he explores the inseparable connection between Beauty and Truth, basing his deepest conviction of the Truth of Christianity on its inherent Beauty, Harmony, and Sweetness. - Summary by Expatriate

11Short History of Wales

By Owen M. Edwards

A Short History of Wales is a book published in 1906 by Owen Edwards. It aimed to provide an introduction to Welsh history, to those who may not have previously dealt with the subject. -Summary by Anonymous

As religion is the great business, for which we are created, and on which our happiness depends; and as religion consists in an intercourse between ourselves and our Maker; and so has its foundation in God's nature and ours, and in the relation that God and we stand in to each other; therefore a true knowledge of both must be needful in order to true religion. But the knowledge of ourselves consists chiefly in right apprehensions concerning those two chief faculties of our nature, the Understanding and Will. Both are very important: yet the science of the latter must be confessed to be of greatest moment; inasmuch as all virtue and religion have their seat more immediately in the will, consisting more especially in right acts and habits of this faculty. And the grand question about the Freedom of the Will, is the main point that belongs to the science of the Will. Therefore I say, the importance of this subject greatly demands the attention of Christians, and especially of Divines. - Summary from the preface

To My Buddies<br> Of the U. S. Army—some three million in number; <br> Of the 90th Division more specifically, and <br> Particularly to the 315th Engineers, to which <br> Regiment I was “attached for rations,” <br> Being a Liability of Company “E,” <br><br> This little Volume is Dedicated. - Summary by Author

14Great Ghost Stories

By Edward Bulwer-Lytton, Amelia Ann Blanford Edwards, Joseph Lewis French, Théophile Gautier, Thomas Hardy, E. T. A. Hoffmann, M. R. James, Frederick Marryat, Fitz-James O'Brien, Margaret O. Oliphant, Sir Arthur Thomas Quiller-Couch and William Sharp

A great collection of 12 classic stories about ghosts and the supernatural. Included are stories by Thomas Hardy, Fitz-James O'Brien, and Margaret Oliphant. Recommended for fans of classic ghost stories of yesteryear. - Summary by Phyllis Vincelli

A biography about David Brainerd, one of the first missionaries to the Native Americans, using excerpts from his diary and journals. This work is an abridged version of the work by Jonathan Edwards, of the same name. - Summary by KHand