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Sample records for impaired hypothalamic-pituitary-adrenal axis

  1. Bile acids modulate glucocorticoid metabolism and the hypothalamic-pituitary-adrenal axis in obstructive jaundice

    DEFF Research Database (Denmark)

    McNeilly, Alison D; Macfarlane, David P; O'Flaherty, Emmett

    2010-01-01

    Suppression of the hypothalamic-pituitary-adrenal axis occurs in cirrhosis and cholestasis and is associated with increased concentrations of bile acids. We investigated whether this was mediated through bile acids acting to impair steroid clearance by inhibiting glucocorticoid metabolism by 5beta-reductase....

  2. Adolescent Survivors of Hurricane Katrina: A Pilot Study of Hypothalamic-Pituitary-Adrenal Axis Functioning

    Science.gov (United States)

    Pfefferbaum, Betty; Tucker, Phebe; Nitiéma, Pascal

    2015-01-01

    Background: The hypothalamic-pituitary-adrenal (HPA) axis constitutes an important biological component of the stress response commonly studied through the measurement of cortisol. Limited research has examined HPA axis dysregulation in youth exposed to disasters. Objective: This study examined HPA axis activation in adolescent Hurricane Katrina…

  3. Hypothalamic-pituitary-adrenal axis activity in older persons with and without a depressive disorder

    NARCIS (Netherlands)

    Rhebergen, D.; Korten, N. C. M.; Penninx, B. W. J. H.; Stek, M. L.; van der Mast, R. C.; Voshaar, R. Oude; Comijs, H. C.

    2015-01-01

    Background: Altered functioning of the hypothalamic-pituitary-adrenal axis (HPA-axis) has been associated with depression, but findings have been inconsistent. Among older depressed persons, both hyperactivity and hypo-activity of the HPA-axis were demonstrated. However, most studies were population

  4. Relationship between the hypothalamic-pituitary-adrenal-axis and fatty acid metabolism in recurrent depression

    NARCIS (Netherlands)

    Mocking, Roel J T; Ruhe, Eric; Assies, Johanna; Lok, Anja; Koeter, Maarten W J; Visser, Ieke; Bockting, Claudi L H; Schene, Aart H

    2013-01-01

    Alterations in hypothalamic-pituitary-adrenal (HPA)-axis activity and fatty acid (FA)-metabolism have been observed in (recurrent) major depressive disorder (MDD). Through the pathophysiological roles of FAs in the brain and cardiovascular system, a hypothesized relationship between HPA-axis activit

  5. Characterization of the hypothalamic-pituitary-adrenal-axis in familial longevity under resting conditions

    NARCIS (Netherlands)

    Jansen, S.W.; Roelfsema, F.; Akintola, A.A.; Oei, N.Y.; Cobbaert, C.M.; Ballieux, B.E.; van der Grond, J.; Westendorp, R.G.; Pijl, H.; van Heemst, D.

    2015-01-01

    Objective: The hypothalamic-pituitary-adrenal (HPA)-axis is the most important neuro-endocrine stress response system of our body which is of critical importance for survival. Disturbances in HPA-axis activity have been associated with adverse metabolic and cognitive changes. Humans enriched for lon

  6. Hypothalamic Pituitary Adrenal Axis Functioning in Reactive and Proactive Aggression in Children

    Science.gov (United States)

    Lopez-Duran, Nestor L.; Olson, Sheryl L.; Hajal, Nastassia J.; Felt, Barbara T.; Vazquez, Delia M.

    2009-01-01

    The purpose of this study was to examine the association between hypothalamic-pituitary-adrenal axis (HPA-axis) reactivity and proactive and reactive aggression in pre-pubertal children. After a 30-min controlled base line period, 73 7-year-old children (40 males and 33 females) were randomly assigned to one of two experimental tasks designed to…

  7. Modelling cholesterol effects on the dynamics of the hypothalamic-pituitary-adrenal (HPA) axis.

    Science.gov (United States)

    Marković, Vladimir M; Čupić, Željko; Maćešić, Stevan; Stanojević, Ana; Vukojević, Vladana; Kolar-Anić, Ljiljana

    2016-03-01

    A mathematical model of the hypothalamic-pituitary-adrenal (HPA) axis with cholesterol as a dynamical variable was derived to investigate the effects of cholesterol, the primary precursor of all steroid hormones, on the ultradian and circadian HPA axis activity. To develop the model, the parameter space was systematically examined by stoichiometric network analysis to identify conditions for ultradian oscillations, determine conditions under which dynamic transitions, i.e. bifurcations occur and identify bifurcation types. The bifurcations were further characterized using numerical simulations. Model predictions agree well with empirical findings reported in the literature, indicating that cholesterol levels may critically affect the global dynamics of the HPA axis. The proposed model provides a base for better understanding of experimental observations, it may be used as a tool for designing experiments and offers useful insights into the characteristics of basic dynamic regulatory mechanisms that, when impaired, may lead to the development of some modern-lifestyle-associated diseases.

  8. Hypothalamic-pituitary-adrenal axis activity and early onset of cannabis use

    NARCIS (Netherlands)

    Huizink, Anja C.; Ferdinand, Robert F.; Ormel, Johan; Verhulst, Frank C.

    2006-01-01

    Aims To identify early onset cannabis users by measuring basal hypothalamic-pituitary-adrenal (HPA) axis activity, which may be a risk factor for early onset substance use when showing low activity. Design In a prospective cohort study, adolescents who initiated cannabis use at an early age (9-12 ye

  9. Acute heat stress impairs performance parameters and induces mild intestinal enteritis in broiler chickens: role of acute hypothalamic-pituitary-adrenal axis activation.

    Science.gov (United States)

    Quinteiro-Filho, W M; Rodrigues, M V; Ribeiro, A; Ferraz-de-Paula, V; Pinheiro, M L; Sá, L R M; Ferreira, A J P; Palermo-Neto, J

    2012-06-01

    Studies on the environmental consequences of stress are relevant for economic and animal welfare reasons. We recently reported that long-term heat stressors (31 ± 1°C and 36 ± 1°C for 10 h/d) applied to broiler chickens (Gallus gallus domesticus) from d 35 to 42 of life increased serum corticosterone concentrations, decreased performance variables and the macrophage oxidative burst, and produced mild, multifocal acute enteritis. Being cognizant of the relevance of acute heat stress on tropical and subtropical poultry production, we designed the current experiment to analyze, from a neuroimmune perspective, the effects of an acute heat stress (31 ± 1°C for 10 h on d 35 of life) on serum corticosterone, performance variables, intestinal histology, and peritoneal macrophage activity in chickens. We demonstrated that the acute heat stress increased serum corticosterone concentrations and mortality and decreased food intake, BW gain, and feed conversion (P 0.05). Increases in the basal and the Staphylococcus aureus-induced macrophage oxidative bursts and a decrease in the percentage of macrophages performing phagocytosis were also observed. Finally, mild, multifocal acute enteritis, characterized by the increased presence of lymphocytes and plasmocytes within the lamina propria of the jejunum, was also observed. We found that the stress-induced hypothalamic-pituitary-adrenal axis activation was responsible for the negative effects observed on chicken performance and immune function as well as for the changes in the intestinal mucosa. The data presented here corroborate with those presented in other studies in the field of neuroimmunomodulation and open new avenues for the improvement of broiler chicken welfare and production performance.

  10. Activation of the hypothalamic-pituitary-adrenal stress axis induces cellular oxidative stress

    Directory of Open Access Journals (Sweden)

    Jereme G. Spiers

    2015-01-01

    Full Text Available Glucocorticoids released from the adrenal gland in response to stress-induced activation of the hypothalamic-pituitary-adrenal (HPA axis induce activity in the cellular reduction-oxidation (redox system. The redox system is a ubiquitous chemical mechanism allowing the transfer of electrons between donor/acceptors and target molecules during oxidative phosphorylation while simultaneously maintaining the overall cellular environment in a reduced state. The objective of this review is to present an overview of the current literature discussing the link between HPA axis-derived glucocorticoids and increased oxidative stress, particularly focussing on the redox changes observed in the hippocampus following glucocorticoid exposure.

  11. The Minimal Model of the Hypothalamic-Pituitary-Adrenal Axis

    DEFF Research Database (Denmark)

    Vinther, Frank; Andersen, Morten; Ottesen, Johnny T.

    2011-01-01

    thereof. The second part of the paper concerns a specific realization of the minimal model in which feedback functions are built explicitly using receptor dynamics. Using physiologically reasonable parameter values, along with the results of the general case, it is demonstrated that un...... that influence the dynamics of the HPA axis, i.e. a negative feedback from cortisol on CRH and ACTH. Therefore we term our model the minimal model. The minimal model, encompasses a wide class of different realizations, obeying only a few physiologically reasonable demands. The results include the existence...... emerge from the model. Sufficient criteria for local stability of the fixed point, and an easily applicable sufficient criteria guaranteeing global stability of the fixed point, is formulated. If the latter is fulfilled, ultradian rhythm is an impossible outcome of the minimal model and all realizations...

  12. Hypothalamic Norepinephrine Mediates Acupunctural Effects on Hypothalamic-Pituitary-Adrenal Axis During Ethanol Withdrawal.

    Science.gov (United States)

    Zhao, Zheng Lin; Kim, Sang Chan; Zhang, Jie; Liu, Hong Feng; Lee, Bong Hyo; Jang, Eun Young; Lee, Chul Won; Cho, Il Je; An, Won G; Yang, Chae Ha; Kim, Young Woo; Zhao, Rong Jie; Wu, Yi Yan

    2016-02-01

    A previous study demonstrated that acupuncture at ST36 (Zu-San-Li) attenuates ethanol withdrawal (EW)-induced hyperactivation of the hypothalamic-pituitary-adrenal axis in rats. The current study investigated the involvement of hypothalamic norepinephrine (NE) in that process. Rats were intraperitoneally treated with 3 g/kg/d of ethanol or saline for 28 days. After 24 hours of EW, acupuncture was applied to rats at bilateral ST36 points or at nonacupoints (tail) for 1 minute. A high-performance liquid chromatography analysis showed that EW significantly increased both the NE and the 3-methoxy-4-hydroxy-phenylglycol (MHPG) levels in the hypothalamic paraventricular nucleus (PVN). Western blot analysis also revealed that EW markedly elevated the phosphorylation rates of tyrosine hydroxylase (TH), but spared TH protein expression in the PVN. However, acupuncture at ST36, but not at nonacupoints, greatly inhibited the increase in the hypothalamic NE, MHPG, and phosphorylation rates of TH. Additionally, postacupuncture infusion of NE into the PVN significantly attenuated the inhibitory effects of acupuncture at ST36 on the oversecretion of plasma corticosterone during EW. These results suggest that acupuncture at ST36 inhibits EW-induced hyperactivation of the hypothalamic NEergic system to produce therapeutic effects on the hypothalamic-pituitary-adrenal axis.

  13. Ontogenetic studies of tolerance development: effects of chronic morphine on the hypothalamic-pituitary-adrenal axis.

    Science.gov (United States)

    Little, P J; Kuhn, C M

    1995-11-01

    Endogenous opiates are important regulators of the hypothalamic-pituitary-adrenal (HPA) axis in rats. Tolerance clearly develops to morphine-induced stimulation of the HPA axis in adult rats (Ignar and Kuhn 1990). The goal of the present study was to determine whether tolerance to morphine-induced stimulation of the HPA axis developed in neonatal and weanling rats treated chronically with morphine. Rats were injected with morphine or saline between days 4-8 postnatal (pups) or days 21-25 (weanlings) and tolerance assessed by determining dose-response curves for ACTH and corticosterone secretion following an acute morphine challenge. Weanlings displayed marked tolerance to the stimulation of ACTH and corticosterone secretion by morphine. Tolerance was also observed in pups to morphine-stimulated ACTH and corticosterone release. These findings suggest that the relative adaptability of the HPA axis to chronic morphine in neonatal and weanling rats is similar.

  14. Update on stress and depression: the role of the hypothalamic-pituitary-adrenal (HPA axis

    Directory of Open Access Journals (Sweden)

    Mello Andrea de Abreu Feijó de

    2003-01-01

    Full Text Available Over the past 50 years, relationships between stress and the neurobiological changes seen in psychiatric disorders have been well-documented. A major focus of investigations in this area has been the role of the hypothalamic-pituitary-adrenal (HPA axis, both as a marker of stress response and as a mediator of additional downstream pathophysiologic changes. This review examines the emerging literature concerning the relationship between stress, HPA axis function, and depression, as well as the role of early life stress as an important risk factor for HPA axis dysregulation. The more recent studies reviewed suggest that the prominence of HPA axis hyperactivity in adults with depressive and anxiety disorders may constitute a link between the occurrence of adversity in childhood and the development of adult psychopathology

  15. Predicting mental disorders from hypothalamic-pituitary-adrenal axis functioning : a 3-year follow-up in the TRAILS study

    NARCIS (Netherlands)

    Nederhof, E.; van Oort, F. V. A.; Bouma, E. M. C.; Laceulle, O. M.; Oldehinkel, A. J.; Ormel, J.

    2015-01-01

    Background. Hypothalamic-pituitary-adrenal axis functioning, with cortisol as its major output hormone, has been presumed to play a key role in the development of psychopathology. Predicting affective disorders from diurnal cortisol levels has been inconclusive, whereas the predictive value of stres

  16. Meta-analysis and meta-regression of hypothalamic-pituitary-adrenal axis activity in functional somatic disorders

    NARCIS (Netherlands)

    Tak, Lineke M; Cleare, Anthony J; Ormel, Johan; Manoharan, Andiappan; Kok, Iris C; Wessely, Simon; Rosmalen, Judith G M

    2011-01-01

    Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis is the most investigated biological risk marker in functional somatic disorders (FSDs), such as chronic fatigue syndrome (CFS), fibromyalgia (FM), and irritable bowel syndrome (IBS). Our aim was to assess whether there is an association be

  17. Anatomy of melancholia: focus on hypothalamic-pituitary-adrenal axis overactivity and the role of vasopressin.

    LENUS (Irish Health Repository)

    Dinan, Timothy G

    2012-02-03

    Overactivity of the hypothalamic-pituitary-adrenal (HPA) axis characterized by hypercortisolism, adrenal hyperplasia and abnormalities in negative feedback is the most consistently described biological abnormality in melancholic depression. Corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) are the main secretagogues of the HPA\\/stress system. Produced in the parvicellular division of the hypothalamic paraventricular nucleus the release of these peptides is influenced by inputs from monoaminergic neurones. In depression, anterior pituitary CRH1 receptors are down-regulated and response to CRH infusion is blunted. By contrast, vasopressin V3 receptors on the anterior pituitary show enhanced response to AVP stimulation and this enhancement plays a key role in maintaining HPA overactivity.

  18. Differential flatness properties and adaptive control of the hypothalamic-pituitary-adrenal axis model

    Science.gov (United States)

    Rigatos, Gerasimos

    2016-12-01

    It is shown that the model of the hypothalamic-pituitary-adrenal gland axis is a differentially flat one and this permits to transform it to the so-called linear canonical form. For the new description of the system's dynamics the transformed control inputs contain unknown terms which depend on the system's parameters. To identify these terms an adaptive fuzzy approximator is used in the control loop. Thus an adaptive fuzzy control scheme is implemented in which the unknown or unmodeled system dynamics is approximated by neurofuzzy networks and next this information is used by a feedback controller that makes the state variables (CRH - corticotropin releasing hormone, adenocortocotropic hormone - ACTH, cortisol) of the hypothalamic-pituitary-adrenal gland axis model converge to the desirable levels (setpoints). This adaptive control scheme is exclusively implemented with the use of output feedback, while the state vector elements which are not directly measured are estimated with the use of a state observer that operates in the control loop. The learning rate of the adaptive fuzzy system is suitably computed from Lyapunov analysis, so as to assure that both the learning procedure for the unknown system's parameters, the dynamics of the observer and the dynamics of the control loop will remain stable. The performed Lyapunov stability analysis depends on two Riccati equations, one associated with the feedback controller and one associated with the state observer. Finally, it is proven that for the control scheme that comprises the feedback controller, the state observer and the neurofuzzy approximator, an H-infinity tracking performance can be succeeded.

  19. Dynamic transitions in a model of the hypothalamic-pituitary-adrenal axis

    Science.gov (United States)

    Čupić, Željko; Marković, Vladimir M.; Maćešić, Stevan; Stanojević, Ana; Damjanović, Svetozar; Vukojević, Vladana; Kolar-Anić, Ljiljana

    2016-03-01

    Dynamic properties of a nonlinear five-dimensional stoichiometric model of the hypothalamic-pituitary-adrenal (HPA) axis were systematically investigated. Conditions under which qualitative transitions between dynamic states occur are determined by independently varying the rate constants of all reactions that constitute the model. Bifurcation types were further characterized using continuation algorithms and scale factor methods. Regions of bistability and transitions through supercritical Andronov-Hopf and saddle loop bifurcations were identified. Dynamic state analysis predicts that the HPA axis operates under basal (healthy) physiological conditions close to an Andronov-Hopf bifurcation. Dynamic properties of the stress-control axis have not been characterized experimentally, but modelling suggests that the proximity to a supercritical Andronov-Hopf bifurcation can give the HPA axis both, flexibility to respond to external stimuli and adjust to new conditions and stability, i.e., the capacity to return to the original dynamic state afterwards, which is essential for maintaining homeostasis. The analysis presented here reflects the properties of a low-dimensional model that succinctly describes neurochemical transformations underlying the HPA axis. However, the model accounts correctly for a number of experimentally observed properties of the stress-response axis. We therefore regard that the presented analysis is meaningful, showing how in silico investigations can be used to guide the experimentalists in understanding how the HPA axis activity changes under chronic disease and/or specific pharmacological manipulations.

  20. Food and the circadian activity of the hypothalamic-pituitary-adrenal axis

    Directory of Open Access Journals (Sweden)

    A.M.O. Leal

    1997-12-01

    Full Text Available Temporal organization is an important feature of biological systems and its main function is to facilitate adaptation of the organism to the environment. The daily variation of biological variables arises from an internal time-keeping system. The major action of the environment is to synchronize the internal clock to a period of exactly 24 h. The light-dark cycle, food ingestion, barometric pressure, acoustic stimuli, scents and social cues have been mentioned as synchronizers or" zeitgebers". The circadian rhythmicity of plasma corticosteroids has been well characterized in man and in rats and evidence has been accumulated showing daily rhythmicity at every level of the hypothalamic-pituitary-adrenal (HPA axis. Studies of restricted feeding in rats are of considerable importance because they reveal feeding as a major synchronizer of rhythms in HPA axis activity. The daily variation of the HPA axis stress response appears to be closely related to food intake as well as to basal activity. In humans, the association of feeding and HPA axis activity has been studied under physiological and pathological conditions such as anorexia nervosa, bulimia, malnutrition, obesity, diabetes mellitus and Cushing's syndrome. Complex neuroanatomical pathways and neurochemical circuitry are involved in feeding-associated HPA axis modulation. In the present review we focus on the interaction among HPA axis rhythmicity, food ingestion, and different nutritional and endocrine states

  1. Hypothalamic-pituitary-adrenal axis responses of horses to therapeutic riding program: effects of different riders.

    Science.gov (United States)

    Fazio, Esterina; Medica, Pietro; Cravana, Cristina; Ferlazzo, Adriana

    2013-06-13

    In order to determine whether therapeutic riding could result in higher levels of stress than recreational riding, hypothalamic-pituitary-adrenal (HPA) axis response was evaluated in six horses by monitoring circulating β-endorphin, ACTH and cortisol concentrations. Horses were already accustomed to be trained both for therapy and riding school activity since 2004. Intervention consisted of 60-minute therapeutic sessions, two times per week for 6weeks with different riders: disabled and recreational riders (session A and B respectively). The therapeutic riders' group (A) consisted of six children with psychomotor disabilities; the recreational riders' group (B) consisted of six healthy children without any previous horse riding experience. Horses were asked to perform the same gaits and exercises at all sessions, both with disabled and healthy users. The statistical analysis showed that during both sessions the mean basal β-endorphin and ACTH levels of horses did not show any significant changes, while the one way RM-ANOVA showed significant effects of sessions A on the cortisol (F=11.50; PHorses submitted to sessions A showed lower cortisol levels both at 5min (Phorses and for the variables settled, HPA axis was less responsive to disabled than healthy, recreational riders. Among the endocrine responses, cortisol was one of the indicators of HPA axis stress response.

  2. Hypothalamic-pituitary-adrenal axis activity in patients with pathological gambling and internet use disorder.

    Science.gov (United States)

    Geisel, Olga; Panneck, Patricia; Hellweg, Rainer; Wiedemann, Klaus; Müller, Christian A

    2015-03-30

    Alterations in secretion of stress hormones within the hypothalamic-pituitary-adrenal (HPA) axis have repeatedly been found in substance-related addictive disorders. It has been suggested that glucocorticoids might contribute to the development and maintenance of substance use disorders by facilitatory effects on behavioral responses to substances of abuse. The objective of this pilot study was to investigate HPA axis activity in patients with non-substance-related addictive disorders, i.e. pathological gambling and internet use disorder. We measured plasma levels of copeptin, a vasopressin surrogate marker, adrenocorticotropic hormone (ACTH) and cortisol in male patients with pathological gambling (n=14), internet use disorder (n=11) and matched healthy controls for pathological gambling (n=13) and internet use disorder (n=10). Plasma levels of copeptin, ACTH and cortisol in patients with pathological gambling or internet use disorder did not differ among groups. However, cortisol plasma levels correlated negatively with the severity of pathological gambling as measured by the PG-YBOCS. Together with our findings of increased serum levels of brain-derived neurotrophic factor (BDNF) in pathological gambling but not internet use disorder, these results suggest that the pathophysiology of pathological gambling shares some characteristics with substance-related addictive disorders on a neuroendocrinological level, whereas those similarities could not be observed in internet use disorder.

  3. Psoriasis severity and hypothalamic-pituitary-adrenal axis function: results from the CALIPSO study

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    A.R. Brunoni

    2014-12-01

    Full Text Available Psoriasis is a chronic inflammatory disease that significantly impacts life quality, being associated with stress and mental disorders. We investigated whether the activity of the hypothalamic-pituitary-adrenal (HPA axis was associated with psoriasis severity, daily life stress and anxiety, and depressive symptoms. In this ancillary study, which was part of the CALIPSO (coronary artery calcium in psoriasis study, saliva was collected from 102 patients with psoriasis immediately upon awakening, 30, and 60 min after awakening, at 2:00 pm and at bedtime (five time points to determine salivary cortisol levels. We used Pearson's correlation coefficient to evaluate the association of clinical and psychopathological variables with HPA activity. We found a direct correlation between bedtime cortisol and psoriasis severity evaluated by the psoriasis area severity index (PASI; r=0.39, P<0.001. No correlations between other clinical and psychopathological variables or with other cortisol assessments were observed. The findings indicated that HPA dysfunction may be present in psoriasis, as bedtime cortisol was correlated with psoriasis severity. Our study is limited by the lack of a control group; therefore, we were not able to explore whether these cortisol values were different compared with a concurrent, healthy sample.

  4. Inclusion of the glucocorticoid receptor in a hypothalamic pituitary adrenal axis model reveals bistability

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    Vernon Suzanne D

    2007-02-01

    Full Text Available Abstract Background The body's primary stress management system is the hypothalamic pituitary adrenal (HPA axis. The HPA axis responds to physical and mental challenge to maintain homeostasis in part by controlling the body's cortisol level. Dysregulation of the HPA axis is implicated in numerous stress-related diseases. Results We developed a structured model of the HPA axis that includes the glucocorticoid receptor (GR. This model incorporates nonlinear kinetics of pituitary GR synthesis. The nonlinear effect arises from the fact that GR homodimerizes after cortisol activation and induces its own synthesis in the pituitary. This homodimerization makes possible two stable steady states (low and high and one unstable state of cortisol production resulting in bistability of the HPA axis. In this model, low GR concentration represents the normal steady state, and high GR concentration represents a dysregulated steady state. A short stress in the normal steady state produces a small perturbation in the GR concentration that quickly returns to normal levels. Long, repeated stress produces persistent and high GR concentration that does not return to baseline forcing the HPA axis to an alternate steady state. One consequence of increased steady state GR is reduced steady state cortisol, which has been observed in some stress related disorders such as Chronic Fatigue Syndrome (CFS. Conclusion Inclusion of pituitary GR expression resulted in a biologically plausible model of HPA axis bistability and hypocortisolism. High GR concentration enhanced cortisol negative feedback on the hypothalamus and forced the HPA axis into an alternative, low cortisol state. This model can be used to explore mechanisms underlying disorders of the HPA axis.

  5. Inflammatory airway features and hypothalamic-pituitary adrenal axis function in asthmatic rats combined with chronic obstructive pulmonary disease

    Institute of Scientific and Technical Information of China (English)

    CAI Cui; CAO Yu-xue; ZHANG Hong-ying; LE Jing-jing; DONG Jing-cheng; CUI Yan; XU Chang-qing; LIU Bao-jun; WU Jin-feng; DUAN Xiao-hong

    2010-01-01

    Background Bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) are both inflammatory airway diseases with different characteristics. However, there are many patients who suffer from both BA and COPD. This study was to evaluate changes of inflammatory airway features and hypothalamic-pituitary-adrenal (HPA) axis function in asthmatic rats combined with COPD.Methods Brown Norway (BN) rats were used to model the inflammatory airway diseases of BA, COPD and COPD+BA.These three models were compared and evaluated with respect to clinical symptoms, pulmonary histopathology, airway hyperresponsiveness (AHR), inflammatory cytokines and HPA axis function.Results The inflammatory airway features and HPA axis function in rats in the COPD+BA model group were greatly influenced. Rats in this model group showed features of the inflammatory diseases BA and COPD. The expression of inflammatory cytokines in this model group might be up or downregulated when both disease processes are present. The levels of corticotrophin releasing hormone mRNA and corticosterone in this model group were both significantly decreased than those in the control group (P <0.05).Conclusions BN rat can be used as an animal model of COPD+BA. By evaluating this animal model we found that the features of inflammation in rats in this model group seem to be exaggerated. The HPA axis functions in rats in this model group have been disturbed or impaired, which is prominent at the hypothalamic level.

  6. Depression, hypothalamic pituitary adrenal axis, and hippocampal and entorhinal cortex volumes--the SMART Medea study.

    Science.gov (United States)

    Gerritsen, Lotte; Comijs, Hannie C; van der Graaf, Yolanda; Knoops, Arnoud J G; Penninx, Brenda W J H; Geerlings, Mirjam I

    2011-08-15

    Structural brain changes have often been found in major depressive disorder (MDD), and it is thought that hypothalamic-pituitary-adrenal (HPA) axis hyperactivity may explain this relation. We investigated the association of MDD and history of depression with hippocampal and entorhinal cortex volumes and whether HPA axis activity explained this association. In 636 participants with a history of atherosclerotic disease (mean age 62 ± 9 years, 81% male) from the second Manifestation of ARTerial disease-Memory depression and aging (SMART-Medea) study, a 12-month diagnosis of MDD and history of depression were assessed. Age of first depressive episode was classified into early-onset depression (< 50 years) and late-onset depression (≥ 50 years). HPA axis regulation was assessed by four morning saliva samples, two evening samples, and one awakening sample after .5 mg dexamethasone. Hippocampus and entorhinal cortex volume were manually outlined on three-dimensional T1-weighted magnetic resonance images. General linear models adjusted for demographics, vascular risk, antidepressant use, and white matter lesions showed that ever having had MDD was associated with smaller hippocampal volumes but not with entorhinal cortex volumes. Remitted MDD was related to smaller entorhinal cortex volumes (p < .05). Participants with early-onset depression had smaller hippocampal volumes than those who were never depressed (p < .05), whereas participants with late-onset depression had smaller entorhinal cortex volumes (p < .05). HPA axis activity did not explain these differences. We found differential associations of age of onset of depression on hippocampal and entorhinal cortex volumes, which could not be explained by alterations in HPA axis regulation. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  7. Hypothalamic-pituitary-adrenal axis function in patients with complex regional pain syndrome type 1.

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    Park, Jai Y; Ahn, Ryun S

    2012-09-01

    An exaggerated inflammatory process is considered an important pathophysiological feature of complex regional pain syndrome type 1 (CRPS-1). The hypothalamic-pituitary-adrenal (HPA) axis serves as a negative feedback mechanism for inflammatory processes. The present study examined the HPA axis function in patients with CRPS-1 by a determination of cortisol concentrations in saliva. Three sets of saliva samples were sequentially collected from 24 patients with CRPS-1 during medication (on-Med), 72 h after stopping medication (off-Med) and 8h after the oral administration of 1mg dexamethasone. One set of saliva samples was collected from healthy controls. The cortisol awakening response (CAR) and diurnal cortisol decline (DCD) were used as indices for HPA axis function. Cortisol levels during the post-awakening period in patients were increased following withdrawal of medications. The CAR during the off-Med condition was disappeared after administration of dexamethasone. Among the examined CRPS-related numerical variables, the frequency of spontaneous pain attacks showed relationships with the indices of HPA axis function. After classifying the patients into two subgroups, we observed that the CAR and DCD in patient who had a relatively high frequency of spontaneous pain attacks (subgroup 5 ≤) were lower and less steep than those in patient who had a relatively low frequency of spontaneous pain attacks (subgroup 0-4) for the on- and off-Med conditions. The CAR and DCD in subgroup 5 ≤ during their off-Med condition were comparable to those in controls. These results suggest that the increase in frequency of spontaneous pain attacks is associated with a reduced CAR and flattened DCD in patients CRPS-1.

  8. Study of hypothalamic pituitary adrenal axis in patients of membranous nephropathy receiving modified Ponticelli regimen

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    R Ramachandran

    2015-01-01

    Full Text Available Pulse methyl prednisolone followed by oral prednisolone and abrupt switch to chlorambucil/cyclophosphamide (Ponticelli/modified Ponticelli regimen is used in patients with idiopathic membranous nephropathy. This therapy where steroids are stopped abruptly is unphysiologic and expected to have hypothalamic pituitary adrenal (HPA axis suppression; however, this has not been evaluated. A total of 13 consecutive adult patients with idiopathic membranous nephropathy who had completed modified Ponticelli regimen were studied. The regimen included administration of pulse methylprednisolone 1 g for 3 days followed by oral prednisolone 0.5 mg/kg/day for 27 days followed by oral cyclophosphamide at a dose of 2 mg/kg/day for the next month. This was repeated for three courses. Patients who had received corticosteroids prior to therapy were excluded. The HPA axis was evaluated after 1 month of completing the last course of steroid therapy. The evaluation was done using a low-dose adrenocorticotropic hormone stimulation test. A single intravenous bolus dose of synacthen (1 μg was given at 9.00 am and the serum cortisol levels were estimated by radioimmunoassay at 0, 30, and 60 min. A peak cortisol level of 550 nmol/L or higher was considered as normal. Mean baseline cortisol levels was 662.3 ± 294.6 nmol/L and peak cortisol level was 767 ± 304.4 nmol/L. A total of 6 patients (46.2% had low basal cortisol levels, only 3 (23% had both basal and peak cortisol levels < 550 nmol/L suggestive of HPA axis suppression. To conclude, 23% of patients had suppression of HPA axis after modified Ponticelli regimen.

  9. Activation of the hypothalamic-pituitary-adrenal axis in adults with mineralocorticoid receptor haploinsufficiency.

    Science.gov (United States)

    Walker, Brian R; Andrew, Ruth; Escoubet, Brigitte; Zennaro, Maria-Christina

    2014-08-01

    Mineralocorticoid receptors (MRs) contribute to the negative feedback of the hypothalamic-pituitary-adrenal (HPA) axis in rodents. Studies with MR antagonists suggest a similar role in humans. The objective of the study was to establish whether loss-of-function mutations in NR3C2, encoding MR, cause activation of the HPA axis. This was a case-control study in members of pedigrees from the PHA1.NET cohort, comprising patients with pseudohypoaldosteronism type 1 (PHA1) who are heterozygous for loss-of-function mutations in NR3C2 and healthy controls who are unaffected family members. Twelve adult patients with PHA1 (six men, six women) and 20 age-matched healthy controls (seven men, 13 women) participated in the study. Patients with PHA1 had higher morning plasma cortisol (816 ± 85 vs 586 ± 50 nmol/L, P = .02) and increased 24-hour urinary excretion of cortisol metabolites (985 ± 150 vs 640 ± 46 μg/mmol creatinine, P = .03), independently of gender. After adjustment for gender, age, PHA1 diagnosis, and percentage body fat, higher plasma cortisol was associated with higher plasma renin, lower serum high-density lipoprotein-cholesterol, and higher waist circumference but not with blood pressure, carotid intima-media thickness, or echocardiographic parameters. Haploinsufficiency of MR in PHA1 causes HPA axis activation, providing genetic evidence that MR contributes to negative feedback in the human HPA axis. With limited sample size, initial indications suggest the resulting hypercortisolemia is related to the severity of MR deficiency and has adverse effects mediated by glucocorticoid receptors on liver lipid metabolism and adipose tissue distribution but does not adversely affect cardiac and vascular remodeling in the absence of normal signaling through the MR.

  10. Hypothalamic-pituitary-adrenal axis response to stress in male DUI recidivists.

    Science.gov (United States)

    Couture, Sophie; Brown, Thomas G; Ouimet, Marie Claude; Gianoulakis, Christina; Tremblay, Jacques; Carbonneau, René

    2008-01-01

    Cortisol is a stress hormone mediated by the hypothalamic-pituitary-adrenal (HPA) axis and a psychobiological marker of genetic risk for alcoholism and other high-risk behavioural characteristics. In previous work with driving under the influence of alcohol (DUI) recidivists, we uncovered a significant inverse relationship between the frequency of past DUI convictions and salivary cortisol, whose strength surpassed those observed between DUI frequency and measures of alcohol abuse and other DUI-related characteristics. This finding emerged using a methodology not specifically contrived to test this relationship. The goals of this follow-up study were to (a) examine if a standardized stress-induction protocol would produce a significant inverse relationship between cortisol response and number of DUI offences; and (b) clarify whether HPA axis dysregulation could be linked to particular DUI-related behavioural correlates, such as alcohol use severity, sensation seeking, and antisocial features. Thirty male DUI recidivists were recruited as well as 11 male non-DUI drivers as a comparison group. Results indicated an inverse relationship between DUI frequency and cortisol response (r(39)=-0.36, p=0.021), as well as a lower cortisol response in DUI offenders than the comparison group (F(1,39)=5.71, p=0.022). Finally, for recidivists, hierarchical regression analyses indicated that experience seeking (R(2)=0.23, p=0.008), followed by number of cigarettes smoked daily ((Delta)R(2)=0.12, p=0.031), combined to explain 35% of the variance in cortisol (F(2,29)=7.26, p=0.003). These findings indicate that severe recidivism may have psychobiological underpinnings, and that HPA axis dysregulation appears to be a mechanism common to high-risk behaviours including DUI recidivism, sensation seeking, and cigarette smoking.

  11. Child mortality, hypothalamic-pituitary-adrenal axis activity and cellular aging in mothers.

    Science.gov (United States)

    Barha, Cindy K; Salvante, Katrina G; Hanna, Courtney W; Wilson, Samantha L; Robinson, Wendy P; Altman, Rachel M; Nepomnaschy, Pablo A

    2017-01-01

    Psychological challenges, including traumatic events, have been hypothesized to increase the age-related pace of biological aging. Here we test the hypothesis that psychological challenges can affect the pace of telomere attrition, a marker of cellular aging, using data from an ongoing longitudinal-cohort study of Kaqchikel Mayan women living in a population with a high frequency of child mortality, a traumatic life event. Specifically, we evaluate the associations between child mortality, maternal telomere length and the mothers' hypothalamic-pituitary-adrenal axis (HPAA), or stress axis, activity. Child mortality data were collected in 2000 and 2013. HPAA activity was assessed by quantifying cortisol levels in first morning urinary specimens collected every other day for seven weeks in 2013. Telomere length (TL) was quantified using qPCR in 55 women from buccal specimens collected in 2013. Shorter TL with increasing age was only observed in women who experienced child mortality (p = 0.015). Women with higher average basal cortisol (p = 0.007) and greater within-individual variation (standard deviation) in basal cortisol (p = 0.053) presented shorter TL. Non-parametric bootstrapping to estimate mediation effects suggests that HPAA activity mediates the effect of child mortality on TL. Our results are, thus, consistent with the hypothesis that traumatic events can influence cellular aging and that HPAA activity may play a mediatory role. Future large-scale longitudinal studies are necessary to confirm our results and further explore the role of the HPAA in cellular aging, as well as to advance our understanding of the underlying mechanisms involved.

  12. Basal hypothalamic pituitary adrenal axis activity and hippocampal volumes: the SMART-Medea study.

    Science.gov (United States)

    Knoops, Arnoud J G; Gerritsen, Lotte; van der Graaf, Yolanda; Mali, Willem P Th M; Geerlings, Mirjam I

    2010-06-15

    It has frequently been hypothesized that high levels of glucocorticoids have deleterious effects on the hippocampus and increase risk for cognitive decline and dementia, but no large-scale studies in humans have examined the direct relation between hippocampal volumes and hypothalamic-pituitary-adrenal axis activity. Cross-sectional analyses within the Second Manifestations of ARTerial disease-Magnetic Resonance (SMART)-Medea study, an ancillary study to the SMART-MR study on brain changes on magnetic resonance imaging (MRI) among patients with arterial disease. In 575 patients (mean age 62 +/- 9 years), diurnal cortisol rhythm was assessed with six saliva samples, collected at awakening; at 30, 45, and 60 min thereafter; and at 10 pm and 11 pm. A low dose of dexamethasone (.5 mg) was administered at 11 pm, and saliva was sampled the next morning at awakening. Volumetric measurements of the hippocampus were performed on a three-dimensional fast field echo T1-weighted scan with isotropic voxels. Mean total relative hippocampal volume was 6.0 +/- .7 mL. Linear regression analyses, adjusted for age, sex, vascular risk factors, and global brain atrophy showed that participants with higher evening levels and higher awakening levels after dexamethasone had smaller hippocampal volumes [B per SD (4.2) increase = -.09 mL; 95% confidence interval -.15 to -.03 mL and B per SD (2.5) increase = -.07 mL; 95% confidence interval -.13 to -.01 mL, respectively]. The awakening response was not significantly associated with hippocampal volumes. In this population, higher evening cortisol levels and reduced suppression after dexamethasone were associated with smaller hippocampal volumes, independent of total brain volume. The cortisol response after awakening was not associated with hippocampal volume.

  13. Renin-Angiotensin-aldosterone system and hypothalamic-pituitary-adrenal axis in hospitalized newborn foals.

    Science.gov (United States)

    Dembek, K A; Onasch, K; Hurcombe, S D A; MacGillivray, K C; Slovis, N M; Barr, B S; Reed, S M; Toribio, R E

    2013-01-01

    The renin-angiotensin-aldosterone system (RAAS) and hypothalamic-pituitary-adrenal axis (HPAA) and their interactions during illness and hypoperfusion are important to maintain organ function. HPAA dysfunction and relative adrenal insufficiency (RAI) are common in septic foals. Information is lacking on the RAAS and mineralocorticoid response in the context of RAI in newborn sick foals. To investigate the RAAS, as well as HPAA factors that interact with the RAAS, in hospitalized foals, and to determine their association with clinical findings. We hypothesized that critical illness in newborn foals results in RAAS activation, and that inappropriately low aldosterone concentrations are part of the RAI syndrome of critically ill foals. A total of 167 foals ≤3 days of age: 133 hospitalized (74 septic, 59 sick nonseptic) and 34 healthy foals. Prospective, multicenter, cross-sectional study. Blood samples were collected on admission. Plasma renin activity (PRA) and angiotensin-II (ANG-II), aldosterone, ACTH, and cortisol concentrations were measured in all foals. ANG-II, aldosterone, ACTH, and cortisol concentrations as well as ACTH/aldosterone and ACTH/cortisol ratios were higher in septic foals compared with healthy foals (P < .05). No difference in PRA between groups was found. High serum potassium and low serum chloride concentrations were associated with hyperaldosteronemia in septic foals. RAAS activation in critically ill foals is characterized by increased ANG-II and aldosterone concentrations. Inappropriately low cortisol and aldosterone concentrations defined as high ACTH/cortisol and ACTH/aldosterone ratios in septic foals suggest that RAI is not restricted to the zona fasciculata in critically ill newborn foals. Copyright © 2013 by the American College of Veterinary Internal Medicine.

  14. Acupoint specificity on acupuncture regulation of hypothalamic- pituitary-adrenal cortex axis function.

    Science.gov (United States)

    Wang, Shao-jun; Zhang, Jiao-jiao; Yang, Hao-yan; Wang, Fang; Li, Si-ting

    2015-03-27

    The hypothalamus is an essential part of the brain that responds to a variety of signaling including stressful stimulations and acupuncture signals. It is also the key element of the hypothalamic-pituitary-adrenal cortex axis(HPAA). The effect of acupuncture is transmitted into the brain from the distance sensory receptor around the acupoints via peripheral nerves and body fluid. In vivo recording the activities of stress reaction neurons (SRNs, CRH-like neurons) in hypothalamic paraventricular nucleus (PVN) in response to the stimulations from different acupoints could therefore objectively reflect the acupuncture afferent effect. In this study, the electrophysiological method was adopted to record synchronously the activities of 43 CRH-like neurons after acupuncture stimulations at 33 acupoints located at the different regions. The acupoints that specifically activate certain CRH-like neurons (specificity acupoints) were selected. Furthermore, we investigated in a rat model of unpredictable chronic mild stress (UCMS) whether these specificity acupoints regulate HPAA function. The endpoints of measurement include corticosterone (CORT) level in peripheral blood, the expressions of corticotrophin releasing hormone (CRH) and glucocorticoid receptor (GR) protein in PVN and the animal behavioral performance. Our results reveal that Shenshu (BL23), Ganshu (BL18), Qimen (LR14), Jingmen (GB25), Riyue (GB24), Zangmen (LR13), Dazui (DU14) and auricular concha region (ACR) are the specificity acupoints; and Gallbladder, Liver and Du Channels were the specificity Channels. The acupoints on Gallbladder Channel and the acupoints innervated by the same spinal cord segments as the adrenal gland demonstrated dramatic effects. This study provides a new platform to further explore acupoints specificity in the regulation of HPAA activities.

  15. Evolutionary functions of early social modulation of hypothalamic-pituitary-adrenal axis development in humans.

    Science.gov (United States)

    Flinn, Mark V; Nepomnaschy, Pablo A; Muehlenbein, Michael P; Ponzi, Davide

    2011-06-01

    The hypothalamic-pituitary-adrenal axis (HPAA) is highly responsive to social challenges. Because stress hormones can have negative developmental and health consequences, this presents an evolutionary paradox: Why would natural selection have favored mechanisms that elevate stress hormone levels in response to psychosocial stimuli? Here we review the hypothesis that large brains, an extended childhood and intensive family care in humans are adaptations resulting from selective forces exerted by the increasingly complex and dynamic social and cultural environment that co-evolved with these traits. Variations in the modulation of stress responses mediated by specific HPAA characteristics (e.g., baseline cortisol levels, and changes in cortisol levels in response to challenges) are viewed as phenotypically plastic, ontogenetic responses to specific environmental signals. From this perspective, we discuss relations between physiological stress responses and life history trajectories, particularly the development of social competencies. We present brief summaries of data on hormones, indicators of morbidity and social environments from our long-term, naturalistic studies in both Guatemala and Dominica. Results indicate that difficult family environments and traumatic social events are associated with temporal elevations of cortisol, suppressed reproductive functioning and elevated morbidity. The long-term effects of traumatic early experiences on cortisol profiles are complex and indicate domain-specific effects, with normal recovery from physical stressors, but some heightened response to negative-affect social challenges. We consider these results to be consistent with the hypothesis that developmental programming of the HPAA and other neuroendocrine systems associated with stress responses may facilitate cognitive targeting of salient social challenges in specific environments. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Hypothalamic-pituitary-adrenal (HPA) axis functioning in relation to body fat distribution.

    Science.gov (United States)

    Rutters, Femke; Nieuwenhuizen, Arie G; Lemmens, Sofie G T; Born, Jurriaan M; Westerterp-Plantenga, Margriet S

    2010-06-01

    To relate hypothalamic-pituitary-adrenal (HPA) axis functioning and HPA feedback functioning to body fat distribution in normal weight to obese subjects. 91 men and 103 women [age 18-45 years, BMI 19-35 kg/m(2), waist-to-hip ratio (WHR) 0.6-1.1]. Anthropometry, body composition using hydrodensitometry and deuterium dilution method, cortisol variability by measuring 5-h cortisol concentrations, HPA axis feedback functioning using a dexamethasone suppression test, and HPA axis functioning under a challenged condition consisting of a standardized high-intensity test with ingestion of 4 mg dexamethasone. In men, an inverse relationship was observed between 5-h cortisol exposure (nmol/ml) and fat mass index (FMI) (kg/m(2)) (r = -0.55, P < 0.001). In women, relationships were observed between 5-h cortisol exposure (nmol/ml.min) and WHR (r = -0.49, P < 0.001), maximal workload (r = 0.32, P < 0.001) as well as oral contraceptive use (r = 0.38, P < 0.001). Similarly, in men, an inverse relationship was observed between negative feedback expressed as baseline concentrations minus post dexamethasone cortisol concentrations (nmol/ml) and FMI (r = -0.53, P < 0.001). In women, relationships were observed between negative feedback expressed as baseline concentrations minus post dexamethasone cortisol concentrations (nmol/ml) and WHR (r = -0.43, P < 0.001), maximal workload (r = 0.30, P < 0.001) as well as oral contraceptive use (r = 0.43, P < 0.001) in women. Moreover, an inverse relationship was observed between HPA axis functioning in a challenged condition expressed as percentage increase of cortisol concentrations after standardized high-intensity test with ingestion of 4 mg dexamethasone (%) and waist circumference (r = -0.21, P < 0.10) in men and WHR (r = -0.21, P < 0.05) in women. In men, strong positive relationships were observed between FMI and waist circumference (r = 0.85, P < 0.001), as well as waist-to-hip ratio (r = 0.70, P < 0.001). Disturbance of HPA axis

  17. Stability analysis of a hypothalamic-pituitary-adrenal axis model with inclusion of glucocorticoid receptor and memory

    Science.gov (United States)

    Kaslik, Eva; Navolan, Dan Bogdan; Neamţu, Mihaela

    2017-01-01

    This paper analyzes a four-dimensional model of the hypothalamic-pituitary-adrenal (HPA) axis that includes the influence of the glucocorticoid receptor in the pituitary. Due to the spatial separation between the hypothalamus, pituitary and adrenal glands, distributed time delays are introduced in the mathematical model. The existence of the positive equilibrium point is proved and a local stability and bifurcation analysis is provided, considering several types of delay kernels. The fractional-order model with discrete time delays is also taken into account. Numerical simulations are provided to illustrate the effectiveness of the theoretical findings.

  18. Can Variation in Hypothalamic-Pituitary-Adrenal (HPA)-Axis Activity Explain the Relationship between Depression and Cognition in Bipolar Patients?

    NARCIS (Netherlands)

    van der Werf-Eldering, MJ; Riemersma-van der Lek, RF; Burger, H.; Holthausen, E.A.E.; Aleman, A.; Nolen, W.A.

    2012-01-01

    Background: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is thought to be associated with more mood symptoms and worse cognitive functioning. This study examined whether variation in HPA axis activity underlies the association between mood symptoms and cognitive functioning. Method

  19. Fatty acid metabolism and its longitudinal relationship with the hypothalamic-pituitary-adrenal axis in major depression : Associations with prospective antidepressant response

    NARCIS (Netherlands)

    Mocking, Roel J. T.; Verburg, Hanka F.; Westerink, Anne M.; Assies, Johanna; Vaz, Frederic M.; Koeter, Maarten W. J.; Ruhe, Henricus G.; Schene, Aart H.

    2015-01-01

    Background: Metabolism of dietary fatty acids (FAs), and its relationship with the hypothalamic-pituitary-adrenal (HPA)-axis, have been found to be altered in major depressive disorder (MDD). Moreover, indications exist that these factors are associated with antidepressant-response. If we better und

  20. Childhood adversity and allostatic overload of the hypothalamic-pituitary-adrenal axis: a vulnerability model for depressive disorders.

    Science.gov (United States)

    Wilkinson, Paul O; Goodyer, Ian M

    2011-11-01

    Childhood adversity is associated with increased risk for onset of depressive episodes. This review will present evidence that allostatic overload of the hypothalamic-pituitary-adrenal axis (HPAA) partially mediates this association. The HPAA is the physiological system that regulates levels of the stress hormone cortisol. First, data from animals and humans has shown that early environmental adversity is associated with long-term dysregulation of the HPAA. This may occur due to permanent epigenetic modification of the glucocorticoid receptor. Second, data from humans has demonstrated that HPAA dysregulation is associated with increased risk of future depression onset in healthy individuals, and pharmacological correction of HPAA dysregulation reduces depressive symptoms. HPAA dysregulation may result in corticoid-mediated abnormalities in neurogenesis in early life and/or neurotoxicity on neural systems that subserve emotion and cognition.

  1. Ketamine and Etomidate Down-regulate the Hypothalamic-Pituitary-Adrenal Axis in an Endotoxemic Mouse Model.

    Science.gov (United States)

    Besnier, Emmanuel; Clavier, Thomas; Tonon, Marie-Christine; Selim, Jean; Lefevre-Scelles, Antoine; Morin, Fabrice; Tamion, Fabienne; Dureuil, Bertrand; Castel, Hélène; Compere, Vincent

    2017-08-01

    We compared the effects of etomidate and ketamine on the hypothalamic-pituitary-adrenal axis during sepsis. Mice (n = 5/group) were injected intraperitoneally with lipopolysaccharide (10 mg/kg) and 6 h later randomized to receive ketamine (100 mg/kg), etomidate (30 mg/kg), or saline. At two time points (12 and 48 h), messenger RNA levels of hypothalamic corticotropin-releasing hormone, pituitary proopiomelanocortin, and four adrenal enzymes (P450 side-chain cleavage, 3β-hydroxysteroid deshydrogenase, 21-hydroxylase, and 11β-hydroxylase) were measured by in situ hybridization (results are presented as optical density), and plasma levels of corticosterone and adrenocorticotropin hormones were measured by enzyme-linked immunosorbent assay (mean ± SD). At 12 h, lipopolysaccharide induced an overexpression of corticotropin-releasing hormone (32 ± 5 vs. 18 ± 6, P ketamine reduced P450 side-chain cleavage (19 ± 7 and 19 ± 3 vs. 32 ± 4, P Ketamine also inhibited adrenocorticotropin hormone production (2.5 ± 3.6 vs. 36 ± 15 pg/ml, P Ketamine and etomidate did not modify corticosterone plasma levels. Our endotoxemic model induces an initial activation of the hypothalamic-pituitary-adrenal axis, followed by a secondary inhibition of adrenal steroidogenesis processes. Ketamine and etomidate inhibit the enzyme expression and activity of the adrenal gland at the early stage.

  2. Skin under the (Spot)-Light: Cross-Talk with the Central Hypothalamic-Pituitary-Adrenal (HPA) Axis.

    Science.gov (United States)

    Jozic, Ivan; Stojadinovic, Olivera; Kirsner, Robert S F; Tomic-Canic, Marjana

    2015-06-01

    UV radiation is among the most prevalent stressors in humans and diurnal rodents, exerting direct and indirect DNA damage, free-radical production, and interaction with specific chromophores that affects numerous biological processes. In addition to its panoply of effects, UVB (290-320 nm) radiation can specifically affect various local neuroendocrine activities by stimulating the expression of corticotropin-releasing hormone (CRH), urocortin, proopiomelanocortin (POMC), and POMC-derived peptides. Although very little is known about the interplay between the central hypothalamic-pituitary-adrenal (HPA) axis and the skin HPA axis analog, in the current issue Skobowiat and Slominski propose a novel mechanism by which exposure to UVB activates a local HPA axis in skin, which in turn activates the central HPA axis, with the requirement of a functional pituitary gland. This is the first evidence of the local HPA axis in skin contributing to the central neuroendocrine response. This raises intriguing possibilities regarding how local production of cortisol and other HPA axis molecules in skin influence overall systemic levels of cortisol and help regulate local and central HPA axes in the context of homeostasis, skin injury, and inflammatory skin disorders.

  3. Cranial irradiation modulates hypothalamic-pituitary-adrenal axis activity and corticosteroid receptor expression in the hippocampus of juvenile rat.

    Science.gov (United States)

    Velickovic, Natasa; Djordjevic, Ana; Drakulic, Dunja; Stanojevic, Ivana; Secerov, Bojana; Horvat, Anica

    2009-01-01

    Glucocorticoids, essential for normal hypothalamic-pituitary-adrenal (HPA) axis activity, exert their action on the hippocampus through two types of corticosteroid receptors: the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). Recent studies report that exposure of juvenile rats to cranial irradiation adversely affects HPA axis stability leading to its activation along with radiation- induced inflammation. This study was aimed to examine the acute effects of radiation on HPA axis activity and hippocampal corticosteroid receptor expression in 18-day-old rats. Since immobilization was part of irradiation procedure, both irradiated and sham-irradiated animals were exposed to this unavoidable stress. Our results demonstrate that the irradiated rats exhibited different pattern of corticosteroid receptor expression and hormone levels compared to respective controls. These differences included upregulation of GR protein in the hippocampus with a concomitant elevation of GR mRNA and an increase in circulating level of corticosterone. In addition, the expression of MR, both at the level of protein and gene expression, was not altered. Taken together, this study demonstrates that cranial irradiation in juvenile rats leads to enhanced HPA axis activity and increased relative GR/MR ratio in hippocampus. The present paper intends to show that neuroendocrine response of normal brain tissue to localized irradiation comprise both activation of HPA axis and altered corticosteroid receptor balance, probably as consequence of innate immune activation.

  4. Total Flavonoids Extracted from Xiaobuxin-Tang on the Hyperactivity of Hypothalamic-Pituitary-Adrenal Axis in Chronically Stressed Rats

    Directory of Open Access Journals (Sweden)

    Lei An

    2011-01-01

    Full Text Available Our previous studies have demonstrated that the total flavonoids (XBXT-2 isolated from the extract of Xiaobuxin-Tang (XBXT, a traditional Chinese herbal decoction, ameliorated behavioral alterations and hippocampal dysfunctions in chronically stressed rats. Studies over the last decades have suggested that the hyperactivity of hypothalamic-pituitary-adrenal (HPA axis is one of the most consistent findings in stress-related depression. Herein, we used the same chronic mild stress model of rats as before to further investigate the effect of XBXT-2 on the hyperactivity of HPA axis, including the stress hormones levels and glucocorticoid receptors (GRs expression. Our ELISA results showed that chronic administration of XBXT-2 (25, 50 mg kg−1, p.o., 28 days, the effective doses for behavioral responses significantly decreased serum corticosterone level and its upstream stress hormone adrenocorticotropic hormone (ACTH level in chronically stressed rats. Furthermore, western blotting result demonstrated XBXT-2 treatment ameliorated stress-induced decrease of GRs expression in hippocampus, an important target involved in the hyperactivity of HPA axis. These results were similar to that of classic antidepressant imipramine treatment (10 mg kg−1, p.o.. In conclusion, the modulation of HPA axis produced by XBXT-2, including the inhibition of stress hormones levels and up-regulation of hippocampal GRs expression, may be an important mechanism underlying its antidepressant-like effect in chronically stressed rats.

  5. Investigating the effect of acute sleep deprivation on hypothalamic-pituitary-adrenal-axis response to a psychosocial stressor.

    Science.gov (United States)

    Vargas, Ivan; Lopez-Duran, Nestor

    2017-05-01

    The hypothalamic-pituitary-adrenal (HPA) axis has been previously identified as one potential mechanism that may explain the link between sleep deprivation and negative health outcomes. However, few studies have examined the direct association between sleep deprivation and HPA-axis functioning, particularly in the context of stress. Therefore, the aim of the current study was to investigate the relationship between acute sleep deprivation and HPA-axis reactivity to a psychosocial stressor. Participants included 40 healthy, young adults between the ages of 18-29. The current protocol included spending two nights in the laboratory. After an adaptation night (night 1), participants were randomized into either a sleep deprivation condition (29 consecutive hours awake) or a control condition (night 2). Following the second night, all participants completed the Trier Social Stress Test (TSST). Salivary cortisol was collected before, during, and after the TSST. Results indicated that there were significant group differences in cortisol stress reactivity. Specifically, compared to participants in the control condition, participants in the sleep deprivation condition had greater baseline (i.e., pre-stress) cortisol, yet a blunted cortisol response to the TSST. Taken together, a combination of elevated baseline cortisol (and its subsequent effect on HPA-axis regulatory processes) and a relative 'ceiling' on the amount of cortisol a laboratory stressor can produce may explain why participants in the sleep deprivation condition demonstrated blunted cortisol responses. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Cortisol reactivity and suicidal behavior: investigating the role of hypothalamic-pituitary-adrenal axis responses to stress in suicide attempters and ideators

    OpenAIRE

    O'Connor, Daryl B.; Green, Jessica A.; Ferguson, Eamonn; O'Carroll, Ronan E.; O'Connor, Rory C.

    2017-01-01

    Every 40 s a person dies by suicide somewhere in the world. The causes of suicidal behavior are not fully understood. Dysregulated hypothalamic-pituitary-adrenal (HPA) axis activity, as measured by cortisol levels, is one potential risk factor. The current study aimed to investigate whether cortisol reactivity to a laboratory stress task differentiated individuals who had previously made a suicide attempt from those who had thought about suicide (suicide ideators) and control participants. On...

  7. Cortisol reactivity and suicidal behavior: investigating the role of hypothalamic-pituitary-adrenal axis responses to stress in suicide attempters and ideators

    OpenAIRE

    O’Connor, Daryl B.; Green, Jessica A.; Ferguson, Eamonn; O’Carroll, Ronan E.; O’Connor, Rory C

    2017-01-01

    Every 40 seconds a person dies by suicide somewhere in the world. The causes of suicidal behavior are not fully understood. Dysregulated hypothalamic-pituitary-adrenal (HPA) axis activity, as measured by cortisol levels, is one potential risk factor. The current study aimed to investigate whether cortisol reactivity to a laboratory stress task differentiated individuals who had previously made a suicide attempt from those who had thought about suicide (suicide ideators) and control participan...

  8. Sleep apnoea and the hypothalamic-pituitary-adrenal axis in men and women: effects of continuous positive airway pressure.

    Science.gov (United States)

    Kritikou, Ilia; Basta, Maria; Vgontzas, Alexandros N; Pejovic, Slobodanka; Fernandez-Mendoza, Julio; Liao, Duanping; Bixler, Edward O; Gaines, Jordan; Chrousos, George P

    2016-02-01

    Previous findings on the association of obstructive sleep apnoea (OSA) and the hypothalamic-pituitary-adrenal (HPA) axis are inconsistent, partly due to the confounding effect of obesity and infrequent sampling. Our goal was to examine whether in a relatively nonobese population, OSA is associated with elevated cortisol levels and to assess the effects of a 2-month placebo-controlled continuous positive airway pressure (sham-CPAP) use.72 subjects (35 middle-aged males and post-menopausal females with OSA, and 37 male and female controls) were studied in the sleep laboratory for four nights. 24-h blood sampling was performed every hour on the fourth day and night in the sleep laboratory at baseline, after sham-CPAP and after CPAP treatment.In both apnoeic men and women, OSA was associated with significantly higher 24-h cortisol levels compared with controls, whereas CPAP lowered cortisol levels significantly, close to those of controls.These results suggest that OSA in nonobese men and slightly obese women is associated with HPA axis activation, similar albeit stronger compared with obese individuals with sleep apnoea. Short-term CPAP use decreased cortisol levels significantly compared with baseline, indicating that CPAP may have a protective effect against comorbidities frequently associated with chronic activation of the HPA axis, e.g. hypertension.

  9. Regulation of 5-HT receptors and the hypothalamic-pituitary-adrenal axis. Implications for the neurobiology of suicide.

    Science.gov (United States)

    López, J F; Vázquez, D M; Chalmers, D T; Watson, S J

    1997-12-29

    Disturbances in the serotonin (5-HT) system is the neurobiological abnormality most consistently associated with suicide. Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis is also described in suicide victims. The HPA axis is the classical neuroendocrine system that responds to stress and whose final product, corticosteroids, targets components of the limbic system, particularly the hippocampus. We will review results from animal studies that point to the possibility that many of the 5-HT receptor changes observed in suicide brains may be a result of, or may be worsened by, the HPA overactivity that may be present in some suicide victims. The results of these studies can be summarized as follows: (1) chronic unpredictable stress produces high corticosteroid levels in rats; (2) chronic stress also results in changes in specific 5-HT receptors (increases in cortical 5-HT2A and decreases in hipocampal 5-HT1A and 5-HT1B); (3) chronic antidepressant administration prevents many of the 5-HT receptor changes observed after stress; and (4) chronic antidepressant administration reverses the overactivity of the HPA axis. If indeed 5-HT receptors have a partial role in controlling affective states, then their modulation by corticosteroids provides a potential mechanism by which these hormones may regulate mood. These data may also provide a biological understanding of how stressful events may increase the risk for suicide in vulnerable individuals and may help us elucidate the neurobiological underpinnings of treatment resistance.

  10. Effects of nutritional stress during different developmental periods on song and the hypothalamic-pituitary-adrenal axis in zebra finches.

    Science.gov (United States)

    Kriengwatana, B; Wada, H; Schmidt, K L; Taves, M D; Soma, K K; MacDougall-Shackleton, S A

    2014-03-01

    In songbirds, developmental stress affects song learning and production. Altered hypothalamic-pituitary-adrenal (HPA) axis function resulting in elevated corticosterone (CORT) may contribute to this effect. We examined whether developmental conditions affected the association between adult song and HPA axis function, and whether nutritional stress before and after nutritional independence has distinct effects on song learning and/or vocal performance. Zebra finches (Taeniopygia guttata) were raised in consistently high (HH) or low (LL) food conditions until post-hatch day (PHD) 62, or were switched from high to low conditions (HL) or vice versa (LH) at PHD 34. Song was recorded in adulthood. We assessed the response of CORT to handling during development and to dexamethasone (DEX) and adrenocorticotropic hormone (ACTH) challenges during adulthood. Song learning and vocal performance were not affected by nutritional stress at either developmental stage. Nutritional stress elevated baseline CORT during development. Nutritional stress also increased rate of CORT secretion in birds that experienced stress only in the juvenile phase (HL group). Birds in the LL group had lower CORT levels after injection of ACTH compared to the other groups, however there was no effect of nutritional stress on the response to DEX. Thus, our findings indicate that developmental stress can affect HPA function without concurrently affecting song.

  11. The total flavonoids extracted from Xiaobuxin Tang reverse the hyperactivity of hypothalamic-pituitary-adrenal axis in chronically stressed rats

    Institute of Scientific and Technical Information of China (English)

    AN Lei; ZHANG You-zhi

    2008-01-01

    Objective To investigate the effect of XBXT-2 on the activity of hypothalamic-pituitary-adrenal (HPA) axis in chronic mild stress (CMS) model of rats. Methods Using ELISA to test the serum corticos-terone, adrenocorticotropic hormone (ACTH) and corticotropin-releasing hormone (CRH) level in CMS rats; Using western blot to determine hippocampal glucocorticoids receptors (GR) expression in CMS rats. Results Co-administration of XBXT-2 (25, 50 mg·kg-1, p. o., 28 days, the effective doses for behavioral responses) significantly decreased the serum corticosterone and ACTH level in CMS rats, while the CRH level was not markedly affected by chronic stress or drugs. Moreover, XBXT-2 significantly increased the GR expression in the hippocampus of CMS rats. The same effects were observed in the positive control drug imipramine ( 10 mg·kg-1 p. o. ). Conclusions The decrease of serum corticosterone and ACTH level, as well as the increase of hippocampal GR expression may be the mechanisms underlying the antidepressant action of XBXT-2, which may associate with HPA axis.

  12. Hair cortisol as a marker of hypothalamic-pituitary-adrenal Axis activity in female patients with major depressive disorder.

    Science.gov (United States)

    Pochigaeva, Ksenia; Druzhkova, Tatiana; Yakovlev, Alexander; Onufriev, Mikhail; Grishkina, Maria; Chepelev, Aleksey; Guekht, Alla; Gulyaeva, Natalia

    2017-04-01

    Hair cortisol is regarded as a promising marker of hypothalamic-pituitary-adrenal axis (HPAA) activity alterations due to stress, somatic and mental health conditions. Hair cortisol was previously reported to be elevated in patients with depression, however the data related to remission and recurrent depressive episodes are different. In this study, levels of hair cortisol were assessed in female patients with major depressive disorder (MDD) and the validity of hair cortisol as a marker of HPAA activity in this condition was evaluated. Hair cortisol was measured in 1 cm hair segments of 21 female patients with MDD and 22 female age-matched controls using enzyme-immunoassay analysis. Concurrently, serum cortisol was assessed and psychological status was evaluated using 17-item Hamilton Depression Rating Scale (HAMD-17), Beck Depression Inventory (BDI) and the Spielberger state trait anxiety inventory (STAI). The levels of hair cortisol were significantly lower in the MDD group, while serum cortisol levels were significantly higher in patients, as compared with controls. A significant negative correlation was found between HAMD-17 scores and hair cortisol. Decreased hair cortisol found in female patients with MDD as compared to controls suggests downregulation of HPAA activity during the preceding month. Further studies are needed to investigate the profiles of hair cortisol at different stages of depressive disorder to establish this parameter as a handy clinical tool.

  13. Hypothalamic-pituitary-adrenal axis response to acute psychosocial stress: Effects of biological sex and circulating sex hormones.

    Science.gov (United States)

    Stephens, Mary Ann C; Mahon, Pamela B; McCaul, Mary E; Wand, Gary S

    2016-04-01

    Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis influences the risk for developing stress-related disorders. Sex-dependent differences in the HPA axis stress response are believed to contribute to the different prevalence rates of stress-related disorders found in men and women. However, studies examining the HPA axis stress response have shown mixed support for sex differences, and the role of endogenous sex hormones on HPA axis response has not been adequately examined in humans. This study utilized the largest sample size to date to analyze the effects of biological sex and sex hormones on HPA axis social stress responses. Healthy, 18- to 30- year-old community volunteers (N=282) completed the Trier Social Stress Test (TSST), a widely used and well-validated stress-induction laboratory procedure. All women (n=135) were tested during the follicular phase of their menstrual cycle (when progesterone levels are most similar to men). Adrenocorticotropic hormone (ACTH) and cortisol measures were collected at multiple points throughout pre- and post-TSST. Testosterone and progesterone (in men) and progesterone and estradiol (in women) were determined pre-TSST. Following the TSST, men had greater ACTH and cortisol levels than women. Men had steeper baseline-to-peak and peak-to-end ACTH and cortisol response slopes than women; there was a trend for more cortisol responders among men than women. Testosterone negatively correlated with salivary cortisol response in men, while progesterone negatively correlated with ACTH and cortisol responses in women. These data confirm that men show more robust activation of the HPA axis response to the TSST than do women in the follicular phase of the menstrual cycle. Testosterone results suggest an inhibitory effect on HPA axis reactivity in men. Progesterone results suggest an inhibitory effect on HPA axis reactivity in women. Future work is needed to explain why men mount a greater ACTH and cortisol response to the

  14. Changes in the maternal hypothalamic-pituitary-adrenal axis during the early puerperium may be related to the postpartum 'blues'.

    Science.gov (United States)

    O'Keane, V; Lightman, S; Patrick, K; Marsh, M; Papadopoulos, A S; Pawlby, S; Seneviratne, G; Taylor, A; Moore, R

    2011-11-01

    Most women experience time-limited and specific mood changes in the days after birth known as the maternity blues (Blues). The maternal hypothalamic-pituitary-adrenal (HPA) axis undergoes gradual changes during pregnancy because of an increasing production of placental corticotrophin-releasing hormone (CRH). The abrupt withdrawal of placental CRH at birth results in a re-equilibration of the maternal HPA axis in the days post-delivery. These changes may be involved in the aetiology of the Blues given the central role of the HPA axis in the aetiology of mood disorders in general, and in perinatal depression in particular. We aimed to test the novel hypothesis that the experience of the Blues may be related to increased secretion of hypothalamic adrenocorticotrophic hormone (ACTH) secretagogue peptides, after the reduction in negative-feedback inhibition on the maternal hypothalamus caused by withdrawal of placental CRH. We therefore examined hormonal changes in the HPA axis in the days after delivery in relation to daily mood changes: our specific prediction was that mood changes would parallel ACTH levels, reflecting increased hypothalamic peptide secretion. Blood concentrations of CRH, ACTH, cortisol, progesterone and oestriol were measured in 70 healthy women during the third trimester of pregnancy, and on days 1-6 post-delivery. Blues scores were evaluated during the postpartum days. Oestriol, progesterone and CRH levels fell rapidly from pregnancy up to day 6, whereas cortisol levels fell modestly. ACTH concentrations declined from pregnancy to day 3 post-delivery and thereafter increased up to day 6. Blues scores increased, peaking on day 5, and were positively correlated with ACTH; and negatively correlated with oestriol levels during the postpartum days, and with the reduction in CRH concentrations from pregnancy. These findings give indirect support to the hypothesis that the 'reactivation' of hypothalamic ACTH secretagogue peptides may be involved in the

  15. Caffeine-induced activated glucocorticoid metabolism in the hippocampus causes hypothalamic-pituitary-adrenal axis inhibition in fetal rats.

    Science.gov (United States)

    Xu, Dan; Zhang, Benjian; Liang, Gai; Ping, Jie; Kou, Hao; Li, Xiaojun; Xiong, Jie; Hu, Dongcai; Chen, Liaobin; Magdalou, Jacques; Wang, Hui

    2012-01-01

    Epidemiological investigations have shown that fetuses with intrauterine growth retardation (IUGR) are susceptible to adult metabolic syndrome. Clinical investigations and experiments have demonstrated that caffeine is a definite inducer of IUGR, as children who ingest caffeine-containing food or drinks are highly susceptible to adult obesity and hypertension. Our goals for this study were to investigate the effect of prenatal caffeine ingestion on the functional development of the fetal hippocampus and the hypothalamic-pituitary-adrenal (HPA) axis and to clarify an intrauterine HPA axis-associated neuroendocrine alteration induced by caffeine. Pregnant Wistar rats were intragastrically administered 20, 60, and 180 mg/kg · d caffeine from gestational days 11-20. The results show that prenatal caffeine ingestion significantly decreased the expression of fetal hypothalamus corticotrophin-releasing hormone. The fetal adrenal cortex changed into slight and the expression of fetal adrenal steroid acute regulatory protein (StAR) and cholesterol side-chain cleavage enzyme (P450scc), as well as the level of fetal adrenal endogenous corticosterone (CORT), were all significantly decreased after caffeine treatment. Moreover, caffeine ingestion significantly increased the levels of maternal and fetal blood CORT and decreased the expression of placental 11β-hydroxysteroid dehydrogenase-2 (11β-HSD-2). Additionally, both in vivo and in vitro studies show that caffeine can downregulate the expression of fetal hippocampal 11β-HSD-2, promote the expression of 11β-hydroxysteroid dehydrogenase 1 and glucocorticoid receptor (GR), and enhance DNA methylation within the hippocampal 11β-HSD-2 promoter. These results suggest that prenatal caffeine ingestion inhibits the development of the fetal HPA axis, which may be associated with the fetal overexposure to maternal glucocorticoid and activated glucocorticoid metabolism in the fetal hippocampus. These results will be beneficial in

  16. Neurobiology of Maternal Stress: Role of Social Rank and Central Oxytocin in Hypothalamic-Pituitary Adrenal Axis Modulation

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    Jeremy D Coplan

    2015-07-01

    Full Text Available Background: Chronic stress may conceivably require plasticity of maternal physiology and behavior to cope with the conflicting primary demands of infant rearing and foraging for food. In addition, social rank may play a pivotal role in mandating divergent homeostatic adaptations in cohesive social groups. We examined cerebrospinal fluid (CSF oxytocin (OT levels and hypothalamic pituitary adrenal (HPA axis regulation in the context of maternal social stress and assessed the contribution of social rank to dyadic-distance as reflective of distraction from normative maternal-infant interaction. Methods: Twelve socially-housed mother-infant bonnet macaque dyads were studied after variable foraging demand (VFD exposure compared to 11 unstressed dyads. Dyadic-distance was determined by behavioral observation. Social ranking was performed blindly by two observers. Post-VFD maternal plasma cortisol and CSF OT were compared to corresponding measures in non-VFD exposed mothers. Results: High social rank was associated with increased dyadic-distance only in VFD-exposed dyads and not in control dyads. In mothers unexposed to VFD, social rank was not related to maternal cortisol levels whereas VFD-exposed dominant versus subordinate mothers exhibited increased plasma cortisol. Maternal CSF OT directly predicted maternal cortisol only in VFD-exposed mothers. CSF OT was higher in dominant versus subordinate mothers. VFD-exposed mothers with high cortisol specifically exhibited CSF OT elevations in comparison to control groups. Conclusions: Pairing of maternal social rank to dyadic-distance in VFD presumably reduces maternal contingent responsivity, with ensuing long-term sequelae. VFD-exposure dichotomizes maternal HPA axis response as a function of social rank with relatively reduced cortisol in subordinates. OT may serve as a homeostatic buffer during maternal stress exposure.

  17. Effects of early childhood trauma on hypothalamic-pituitary-adrenal (HPA) axis function in patients with Chronic Fatigue Syndrome.

    Science.gov (United States)

    Kempke, Stefan; Luyten, Patrick; De Coninck, Sarah; Van Houdenhove, Boudewijn; Mayes, Linda C; Claes, Stephan

    2015-02-01

    There is a paucity of studies that have investigated the assumption that early childhood trauma is associated with hypothalamic-pituitary-adrenal (HPA) axis dysfunction in Chronic Fatigue Syndrome (CFS). The current study is the first to simultaneously investigate relationships among early childhood trauma, cortisol activity, and cortisol stress reactivity to psychosocial stress in a sample of well-screened CFS patients. We also examined whether self-critical perfectionism (SCP) plays a mediating role in the potential relationship between early trauma and neurobiological stress responses. A total of 40 female patients diagnosed with CFS were asked to provide morning saliva cortisol samples (after awakening, 30min later, and 1h later) for seven consecutive days as a measure of cortisol activity. In addition, patients were exposed to the Trier Social Stress Test, a well-validated stress test, to investigate the relationship between early childhood trauma and cortisol stress reactivity. Before the start of the study, patients completed the Childhood Trauma Questionnaire-Short form (CTQ-SF) as a measure of early childhood trauma (i.e. sexual, physical and emotional traumatic experiences). SCP was measured with the Depressive Experiences Questionnaire (DEQ). Data were analyzed by calculating several indices of cortisol secretion (i.e. Cortisol Awakening Response and Area Under the Curve). There was no association between early childhood trauma and cortisol as measured over the 7-day period. However, emotional neglect was significantly negatively related to cortisol reactivity in the TSST. SCP did not significantly mediate this association. Findings of this study suggest that emotional neglect is associated with blunted HPA axis reactivity, congruent with the assumption that CFS may reflect loss of adaptability of the neuroendocrine stress response system in at least a subgroup of patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Disturbances in Hypothalamic-Pituitary-Adrenal Axis and Immunological Activity Differentiating between Unipolar and Bipolar Depressive Episodes.

    Directory of Open Access Journals (Sweden)

    Karlijn Becking

    Full Text Available Differentiating bipolar depression (BD from unipolar depression (UD is difficult in clinical practice and, consequently, accurate recognition of BD can take as long as nine years. Research has therefore focused on the discriminatory capacities of biomarkers, such as markers of the hypothalamic-pituitary-adrenal (HPA axis or immunological activity. However, no previous study included assessments of both systems, which is problematic as they may influence each other. Therefore, this study aimed to explore whether cortisol indicators and inflammatory markers were a independently associated with and/or b showed effect modification in relation to a lifetime (hypomanic episode in a large sample of depressed patients.Data were derived from the Netherlands Study of Depression and Anxiety and comprised 764 patients with a DSM-IV depressive disorder at baseline, of which 124 (16.2% had a lifetime (hypomanic episode at the 2-year assessment, or a more recent episode at the 4-year or 6-year assessment. Baseline cortisol awakening response, evening cortisol and diurnal cortisol slope were considered as cortisol indicators, while baseline C-reactive Protein (CRP, Interleukin-6 (IL-6, and Tumor Necrosis Factor Alpha (TNF-α were included as inflammatory markers.In depressed men and women, none of the cortisol indicators and inflammatory markers were (independently associated with a (hypomanic episode. However, effect modification was found of diurnal cortisol slope and CRP in relation to a (hypomanic episode. Further analyses showed that depressed men with high levels of diurnal cortisol slope and CRP had an increased odds (OR=10.99, p=.001 of having a (hypomanic episode. No significant differences were found in women.Our findings suggest that the combination of high diurnal cortisol slope and high CRP may differentiate between UD and BD. This stresses the importance of considering HPA-axis and immunological activity simultaneously, but more research is needed

  19. Effects of corticotropin-releasing factor 1 receptor antagonism on the hypothalamic-pituitary-adrenal axis of rodents.

    Science.gov (United States)

    Gehlert, Donald R; Cramer, Jeffrey; Morin, S Michelle

    2012-06-01

    Corticotropin-releasing factor (CRF) is the major hypothalamic neuropeptide responsible for stimulation of the hypothalamic-pituitary-adrenal axis (HPAA), resulting in the synthesis and release of glucocorticoids from the adrenal cortex. In a recent study, we reported the discovery of the CRF1 receptor antagonist, 3-(4-chloro-2-morpholin-4-yl-thiazol-5-yl)-8-(1-ethylpropyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (MTIP), which has efficacy in preclinical models of stress-induced alcohol consumption. Because CRF1 is important in HPAA activation, we evaluated the effects of MTIP administration on rodent HPAA function. Initial studies established the MTIP doses required for brain and pituitary CRF1 occupancy and those associated with the inhibition of intracerebroventricular CRF on the HPAA in mice. Then, rat basal plasma corticosterone (CORT) concentrations were measured hourly by radioimmunoassay for 24 h after three daily doses of MTIP or vehicle. In these studies, the early phase of the nocturnal CORT surge was reduced; however, the area under the CORT curve was identical for the 24-h period. In subsequent studies, increases in plasma CORT due to direct pharmacological manipulation of the HPAA axis or by stressors were evaluated after MTIP treatment in mice. MTIP attenuated CORT responses generated by immediate bolus administration of insulin or ethanol; however, MTIP did not affect activation of the HPAA by other stressors and pharmacological agents. Therefore, MTIP can modulate basal HPAA activity during the CORT surge and reduced activation after a select number of stressors but does not produce a lasting suppression of basal CORT. The ability of MTIP to modulate plasma CORT after hyperinsulinemia may provide a surrogate strategy for a target occupancy biomarker.

  20. Estrogen alters baseline and inflammatory-induced cytokine levels independent from hypothalamic-pituitary-adrenal axis activity.

    Science.gov (United States)

    Shivers, Kai-Yvonne; Amador, Nicole; Abrams, Lisa; Hunter, Deirtra; Jenab, Shirzad; Quiñones-Jenab, Vanya

    2015-04-01

    Although estrogen reduces inflammatory-mediated pain responses, the mechanisms behind its effects are unclear. This study investigated if estrogen modulates inflammatory signaling by reducing baseline or inflammation-induced cytokine levels in the injury-site, serum, dorsal root ganglia (DRG) and/or spinal cord. We further tested whether estrogen effects on cytokine levels are in part mediated through hypothalamic-pituitary-adrenal (HPA) axis activation. Lumbar DRG, spinal cord, serum, and hind paw tissue were analyzed for cytokine levels in 17β-estradiol-(20%) or vehicle-(100% cholesterol) treated female rats following ovariectomy/sham adrenalectomy (OVX), adrenalectomy/sham ovariectomy (ADX) or ADX+OVX operation at baseline and post formalin injection. Formalin significantly increased pro-inflammatory interleukin (IL)-6 levels in the paw, as well as pro- and anti-inflammatory cytokine levels in the DRG, spinal cord and serum in comparison to naïve conditions. Estrogen replacement significantly increased anti-inflammatory IL-10 levels in the DRG. Centrally, estradiol significantly decreased pro-inflammatory tumor necrosis factor (TNF)-α and IL-1β levels, as well as IL-10 levels, in the spinal cord in comparison to cholesterol treatment. At both sites, most estradiol modulatory effects occurred irrespective of pain or surgical condition. Estradiol alone had no influence on cytokine release in the paw or serum, indicating that estrogen effects were site-specific. Although cytokine levels were altered between surgical conditions at baseline and following formalin administration, ADX operation did not significantly reverse estradiol's modulation of cytokine levels. These results suggest that estrogen directly regulates cytokines independent of HPA axis activity in vivo, in part by reducing cytokine levels in the spinal cord.

  1. Decreased maternal hypothalamic-pituitary-adrenal axis activity in very severely obese pregnancy: Associations with birthweight and gestation at delivery.

    Science.gov (United States)

    Stirrat, Laura I; O'Reilly, James R; Barr, Sarah M; Andrew, Ruth; Riley, Simon C; Howie, Alexander F; Bowman, Maria; Smith, Roger; Lewis, John G; Denison, Fiona C; Forbes, Shareen; Seckl, Jonathan R; Walker, Brian R; Norman, Jane E; Reynolds, Rebecca M

    2016-01-01

    The maternal hypothalamic-pituitary-adrenal-axis (HPAA) undergoes dramatic activation during pregnancy. Increased cortisol and corticotrophin-releasing-hormone (CRH) associate with low birthweight and preterm labor. In non-pregnant obesity, the HPAA is activated but circulating cortisol levels are normal or lower than in lean women. We hypothesized that maternal cortisol levels would be lower in obese pregnancy, and would associate with increased fetal size and length of gestation. Fasting serum cortisol was measured at 16, 28 and 36 weeks gestation and at 3-6 months postpartum in 276 severely obese and 135 lean women. In a subset of obese (n=20) and lean (n=20) we measured CRH, hormones that regulate bioavailable cortisol (corticosteroid-binding-globulin, estradiol, estriol, and progesterone). Urinary glucocorticoid metabolites were measured in pregnant (obese n=6, lean n=5) and non-pregnant (obese n=7, lean n=7) subjects. Maternal cortisol and HPAA hormones were lower in obese pregnancy. Total urinary glucocorticoid metabolites increased significantly in lean pregnancy, but not in obese. Lower maternal cortisol in obese tended to be associated with increased birthweight (r=-0.13, p=0.066). In obese, CRH at 28 weeks correlated inversely with gestational length (r=-0.49, p=0.04), and independently predicted gestational length after adjustment for confounding factors (mean decrease in CRH of -0.25 pmol/L (95% CI -0.45 to -0.043 pmol/L) per/day increase in gestation). In obese pregnancy, lower maternal cortisol without an increase in urinary glucocorticoid clearance may indicate a lesser activation of the HPAA than in lean pregnancy. This may offer a novel mechanism underlying increased birthweight and longer gestation in obese pregnancy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Hypothalamic-pituitary adrenal (HPAA) axis function in adult Fischer-344 rats exposed during development to neurotoxic chemicals perinatally.

    Science.gov (United States)

    Rosecrans, J A; Johnson, J H; Tilson, H A; Hong, J S

    1984-01-01

    The major objective of these experiments was to determine long-term effects on the hypothalamic-pituitary adrenal axis (HPAA) of adult rats exposed during development to chlordecone, an organochlorine insecticide. Chlordecone was administered to mothers prenatally plus the first 12 days of the neonatal period (6 ppm in the diet) or neonatally via a single subcutaneous injection to rats at 4 days of age (1 mg/pup in 20 micrograms of DMSO). DMSO (20 microliters/pup) and dexamethasone (100 micrograms/pup in 20 microliters saline) were also injected on day 4. HPAA function was evaluated at 70-80 days of age. Responsiveness of the HPAA to a repeated stressor was evaluated by exposing rats of each treatment group to a 7-day stress-induced analgesia (SIA) paradigm consisting of a daily 15 sec foot-shock (0.9 mA) exposure which was preceded by a 15 sec white noise conditioned stimulus. The behavioral response to daily stress was evaluated by measuring tail-flick latencies immediately before and/or after each stress exposure. The conditioned response to stress was evaluated 24 hours after the last of 7 daily foot-shock sessions in which rats of each treatment and experimental group were exposed to the shock chamber only. All rats were killed 15 minutes after the final session and tissue (serum and adrenals) were removed and frozen for later chemical analysis; serum and adrenal corticosterone (CS) and serum prolactin (Prl) levels were measured. Perinatal exposure to chlordecone did not significantly alter the behavioral and/or neuroendocrine responses to stress. Ambient hormone levels (both CS and Prl), however, were uniformly attenuated by chlordecone.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Environmental enrichment mitigates the sex-specific effects of gestational inflammation on social engagement and the hypothalamic pituitary adrenal axis-feedback system.

    Science.gov (United States)

    Connors, E J; Shaik, A N; Migliore, M M; Kentner, A C

    2014-11-01

    Modest environmental enrichment (EE) is well recognized to protect and rescue the brain from the consequences of a variety of insults. Although animal models of maternal immune activation (MIA) are associated with several neurodevelopmental impairments in both the behavioral and cognitive functioning of offspring, the impact of EE in protecting or reversing these effects has not been fully evaluated. In the present study, female Sprague-Dawley rats were randomized into EE (pair-housed in a large multi-level cage with toys, tubes and ramps) or animal care control (ACC; pair-housed in standard cages) conditions. Each pair was bred, following assignment to their housing condition, and administered 100μg/kg of lipopolysaccharide (LPS) on gestational day 11. After birth, and until the end of the study, offspring were maintained in their respective housing conditions. EE protected against both the social and hypothalamic pituitary adrenal axis consequences of MIA in juvenile male rats, but surprisingly not against the spatial discrimination deficits or accompanying decrease in glutamate levels within the hippocampus (as measured via LCMS-MS). Based on these preliminary results, the mechanisms that underlie the sex-specific consequences that follow MIA appear to be dependent on environmental context. Together, this work highlights the importance of environmental complexity in the prevention of neurodevelopmental deficits following MIA.

  4. Brain Mast Cells Act as an Immune Gate to the Hypothalamic-Pituitary-Adrenal Axis in Dogs

    OpenAIRE

    Matsumoto, Itsuro; Inoue, Yasuhisa; Shimada, Toshio; Aikawa, Tadaomi

    2001-01-01

    Mast cells perform a significant role in the host defense against parasitic and some bacterial infections. Here we show that in the dog, degranulation of brain mast cells evokes hypothalamic-pituitary-adrenal responses via histamine release. A large number of mast cells were found in a circumscribed ventral region of the hypothalamus, including the pars tuberalis and median eminence. When these intracranial mast cells were passively sensitized with immunoglobulin E via either the intracerebro...

  5. Expression of genes related to the hypothalamic-pituitary-adrenal axis in murine fetal lungs in late gestation

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    Côté Mélissa

    2010-11-01

    Full Text Available Abstract Background Lung maturation is modulated by several factors, including glucocorticoids. Expression of hypothalamic-pituitary-adrenal (HPA axis-related components, with proposed or described local regulatory systems analogous to the HPA axis, was reported in peripheral tissues. Here, HPA axis-related genes were studied in the mouse developing lung during a period overlapping the surge of surfactant production. Methods Expression of genes encoding for corticotropin-releasing hormone (CRH, CRH receptors (CRHR 1 and 2beta, CRH-binding protein, proopiomelanocortin (POMC, melanocortin receptor 2 (MC2R, and glucocorticoid receptor was quantified by real-time PCR and localized by in situ hydridization in fetal lungs at gestational days (GD 15.5, 16.5, and 17.5, and was also quantified in primary mesenchymal- and epithelial cell-enriched cultures. In addition, the capability of CRH and adrenocorticotropic hormone (ACTH to stimulate pulmonary expression of enzymes involved in the adrenal pathway of glucocorticoid synthesis was addressed, as well as the glucocorticoid production by fetal lung explants. Results We report that all the studied genes are expressed in fetal lungs according to different patterns. On GD 15.5, Mc2r showed peaks in expression in samples that have previously presented high mRNA levels for glucocorticoid synthesizing enzymes, including 11beta-hydroxylase (Cyp11b1. Crhr1 mRNA co-localized with Pomc mRNA in cells surrounding the proximal epithelium on GD 15.5 and 16.5. A transition in expression sites toward distal epithelial cells was observed between GD 15.5 and 17.5 for all the studied genes. CRH or ACTH stimulation of genes involved in the adrenal pathway of glucocorticoid synthesis was not observed in lung explants on GD 15.5, whereas CRH significantly increased expression of 21-hydroxylase (Cyp21a1 on GD 17.5. A deoxycorticosterone production by fetal lung explants was observed. Conclusions Temporal and spatial

  6. Hypothalamic-Pituitary-Adrenal Axis Programming after Recurrent Hypoglycemia during Development

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    Raghavendra Rao

    2015-08-01

    Full Text Available Permanent brain injury is a complication of recurrent hypoglycemia during development. Recurrent hypoglycemia also has adverse consequences on the neuroendocrine system. Hypoglycemia-associated autonomic failure, characterized by ineffective glucose counterregulation during hypoglycemia, is well described in children and adults on insulin therapy for diabetes mellitus. Whether recurrent hypoglycemia also has a programming effect on the hypothalamus-pituitary-adrenal cortex (HPA axis has not been well studied. Hypoglycemia is a potent stress that leads to increased glucocorticoid secretion in all age groups, including the perinatal period. Other conditions associated with exposure to excess glucocorticoid in the perinatal period have a programming effect on the HPA axis activity. Limited animal data suggest the possibility of similar programming effect after recurrent hypoglycemia in the postnatal period. The age at exposure to hypoglycemia likely determines the HPA axis response in adulthood. Recurrent hypoglycemia in the early postnatal period likely leads to a hyperresponsive HPA axis, whereas recurrent hypoglycemia in the late postnatal period lead to a hyporesponsive HPA axis in adulthood. The age-specific programming effects may determine the neuroendocrine response during hypoglycemia and other stressful events in individuals with history of recurrent hypoglycemia during development.

  7. Characterization of the Hypothalamic-Pituitary-Adrenal-Axis in Familial Longevity under Resting Conditions

    DEFF Research Database (Denmark)

    Jansen, Steffy W; Roelfsema, Ferdinand; Akintola, Abimbola A;

    2015-01-01

    of the HPA-axis in offspring from long-lived siblings, who are enriched for familial longevity and age-matched controls. DESIGN: Case-control study within the Leiden Longevity study cohort consisting of 20 middle-aged offspring of nonagenarian siblings (offspring) together with 18 partners (controls...... for longevity have less metabolic and cognitive disturbances and therefore diminished activity of the HPA axis may be a potential candidate mechanism underlying healthy familial longevity. Here, we compared 24-h plasma ACTH and serum cortisol concentration profiles and different aspects of the regulation...... not differ between offspring and controls. In addition, no significant differences in feedforward and feedback synchrony and adrenal gland ACTH responsivity were observed between groups. CONCLUSIONS: These results suggest that familial longevity is not associated with major differences in HPA-axis activity...

  8. Hypothalamic-pituitary-adrenal axis tonus is associated with hippocampal microstructural asymmetry

    DEFF Research Database (Denmark)

    Madsen, Kathrine Skak; Jernigan, Terry L; Iversen, Pernille

    2012-01-01

    It is well-established that prolonged high levels of cortisol have adverse effects on hippocampal neurons and glial cells. Morphometric studies linking hippocampus volume to basal HPA-axis activity, however, have yielded less consistent results. Asymmetry may also be considered, since there is gr...

  9. Activation of the Hypothalamic-Pituitary-Adrenal (HPA) Axis Following Extended Exposure to Atrazine (ATR)###

    Science.gov (United States)

    While it is known that adrenal steroids impact reproduction and a variety of other physiological and behavioral functions, disruption of the HPA-axis is not typically considered in toxicological studies. Here we characterize changes in basal corticosterone (CORT) and progesterone...

  10. Activation of the Hypothalamic-Pituitary-Adrenal (HPA) Axis Following Extended Exposure to Atrazine (ATR)

    Science.gov (United States)

    While it is known that adrenal steroids impact reproduction and a variety of other physiological and behavioral fimctions, disruption of the HPA-axis is not typically considered in toxicological studies. Here we characterize changes in basal corticosterone (CORT) and progesterone...

  11. Activation of the Hypothalamic-Pituitary-Adrenal (HPA) Axis Following Extended Exposure to Atrazine (ATR)###

    Science.gov (United States)

    While it is known that adrenal steroids impact reproduction and a variety of other physiological and behavioral functions, disruption of the HPA-axis is not typically considered in toxicological studies. Here we characterize changes in basal corticosterone (CORT) and progesterone...

  12. Activation of the Hypothalamic-Pituitary-Adrenal (HPA) Axis Following Extended Exposure to Atrazine (ATR)

    Science.gov (United States)

    While it is known that adrenal steroids impact reproduction and a variety of other physiological and behavioral fimctions, disruption of the HPA-axis is not typically considered in toxicological studies. Here we characterize changes in basal corticosterone (CORT) and progesterone...

  13. Recovery of the hypothalamic-pituitary-adrenal axis in children and adolescents after surgical cure of Cushing's disease.

    Science.gov (United States)

    Lodish, Maya; Dunn, Somya Verma; Sinaii, Ninet; Keil, Margaret F; Stratakis, Constantine A

    2012-05-01

    Recovery of the hypothalamic-pituitary-adrenal axis (HPAA) after transsphenoidal surgery (TSS) for Cushing's disease (CD) in children has not been adequately studied. Our objective was to assess time to recovery of the HPAA after TSS in children with CD. This was a case series at the National Institutes of Health Clinical Center. Fifty-seven patients with CD (6-18 yr, mean 13.0 ± 3.1 yr) given a standard regimen of glucocorticoid tapering after TSS were studied out of a total of 73 recruited. ACTH (250 μg) stimulation tests were administered at approximately 6-month intervals for up to 36 months. Age, sex, pubertal status, body mass index, length of disease, midnight cortisol, and urinary free cortisol at diagnosis were analyzed for effects on recovery. The main outcome measure was complete recovery of the HPAA as defined by a cortisol level of at least 18 μg/dl in response to 250 μg ACTH. Full recovery was reached by 43 (75.4%) of 57 patients, with 29 of the 43 (67.4%) and 41 of the 43 (95.3%) recovering by 12 and 18 months, respectively. The overall mean time to recovery was 12.6 ± 3.3 months. Kaplan-Meier survivor function estimated a 50% chance of recovering by 12 months after TSS and 75% chance of recovering within 14 months. By receiver operating characteristic curve assessment, the cutoff of at least 10-11 μg/dl of cortisol as the peak of ACTH stimulation testing at 6 months after TSS yielded the highest sensitivity (70-80%) and specificity (64-73%) to predict full recovery of the HPAA at 12 months. Two of the four patients that recovered fully within 6 months had recurrent CD. Although this is not a randomized study, we present our standardized tapering regimen for glucocorticoid replacement after TSS that led to recovery of the HPAA in most patients within the first postoperative year. Multiple factors may affect this process, but an early recovery may indicate disease recurrence.

  14. Hypothalamic-Pituitary-Adrenal Axis Function in Dissociative Disorders, PTSD, and Healthy Volunteers

    Science.gov (United States)

    Simeon, Daphne; Knutelska, Margaret; Yehuda, Rachel; Putnam, Frank; Schmeidler, James; Smith, Lisa M.

    2007-01-01

    Background This study investigated basal and stress-induced HPA axis alterations in dissociative disorders (DD). Methods Forty-six subjects with DD without lifetime PTSD, 35 subjects with PTSD, and 58 HC subjects, free of current major depression, were studied as inpatients. After a 24-hour urine collection and hourly blood sampling for ambient cortisol determination, a low-dose dexamethasone suppression test was administered, followed by the Trier Social Stress Test. Results The DD group had significantly elevated urinary cortisol compared to the HC group, more pronounced in the absence of lifetime major depression, whereas the PTSD and HC groups did not differ. The DD group demonstrated significantly greater resistance to, and faster escape from, dexamethasone suppression compared to the HC group, whereas the PTSD and HC groups did not differ. The three groups did not differ in cortisol stress reactivity, but both psychiatric groups demonstrated a significant inverse correlation between dissociation severity and cortisol reactivity, after controlling for all other symptomatology. The PTSD subgroup with comorbid DD tended to have blunted reactivity compared to the HC group. Conclusions The study demonstrates a distinct pattern of HPA axis dysregulation in DD, emphasizing the importance of further study of stress response systems in dissociative psychopathology. PMID:17137559

  15. Sound conditioning protects hearing by activating the hypothalamic-pituitary-adrenal axis.

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    Tahera, Yeasmin; Meltser, Inna; Johansson, Peter; Salman, Hazim; Canlon, Barbara

    2007-01-01

    Sound conditioning primes the auditory system to low levels of acoustic stimuli and reduces damage caused by a subsequent acoustic trauma. This priming activates the HPA axis resulting in the elevation of plasma corticosterone with a consequent upregulation of glucocorticoid receptors (GR) in the cochlea and the paraventricular nucleus (PVN) of the hypothalamus in the mouse. This protective effect is blocked by adrenalectomy or pharmacological treatment with RU486 + metyrapone. Sound conditioning prevents GR down-regulation induced by acoustic trauma and subsequently enhances GR activity in spiral ganglion neurons. Increased SRC-1 expression, triggered by sound conditioning, positively correlates with the upregulation of GR in the cochlea. These findings will help to define the cellular mechanisms responsible for protecting the auditory system from hearing loss by sound conditioning.

  16. The Recovery of Hypothalamic-Pituitary-Adrenal Axis Is Rapid in Subclinical Cushing Syndrome.

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    Kim, Hee Kyung; Yoon, Jee Hee; Jeong, Yun Ah; Kang, Ho Cheol

    2016-12-01

    In subclinical Cushing syndrome (SC), it is assumed that glucocorticoid production is insufficient to cause a clinically recognizable syndrome. Differences in hormonal levels or recovery time of the hypothalamic-pituitary-adrenocortical (HPA) axis after adrenalectomy between patients with overt Cushing syndrome (OC) and SC remain unknown. Thirty-six patients (10 with OC and 26 with SC) with adrenal Cushing syndrome who underwent adrenalectomy from 2004 to 2014 were reviewed retrospectively. Patients were treated with glucocorticoid after adrenalectomy and were reevaluated every 1 to 6 months using a rapid adrenocorticotropic hormone (ACTH) stimulation test. Levels of basal 24-hour urine free cortisol (UFC), serum cortisol after an overnight dexamethasone suppression test (DST), and serum cortisol and 24-hour UFC after low-dose DST and high-dose DST were all significantly lower in patients with SC compared with OC. Basal ACTH levels showed significantly higher in patients with SC compared with OC. The probability of recovering adrenal function during follow-up differed significantly between patients with OC and SC (P=0.001), with significant correlations with the degree of preoperative cortisol excess. Patients with OC required a longer duration of glucocorticoid replacement to recover a normal ACTH stimulation test compared with patients with SC (median 17.0 months vs. 4.0 months, P<0.001). The HPA axis recovery time after adrenalectomy in patients with SC is rapid and is dependent on the degree of cortisol excess. More precise definition of SC is necessary to achieve a better management of patients and to avoid the risk of under- or over-treatment of SC patients.

  17. The Recovery of Hypothalamic-Pituitary-Adrenal Axis Is Rapid in Subclinical Cushing Syndrome

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    Hee Kyung Kim

    2016-12-01

    Full Text Available BackgroundIn subclinical Cushing syndrome (SC, it is assumed that glucocorticoid production is insufficient to cause a clinically recognizable syndrome. Differences in hormonal levels or recovery time of the hypothalamic-pituitary-adrenocortical (HPA axis after adrenalectomy between patients with overt Cushing syndrome (OC and SC remain unknown.MethodsThirty-six patients (10 with OC and 26 with SC with adrenal Cushing syndrome who underwent adrenalectomy from 2004 to 2014 were reviewed retrospectively. Patients were treated with glucocorticoid after adrenalectomy and were reevaluated every 1 to 6 months using a rapid adrenocorticotropic hormone (ACTH stimulation test.ResultsLevels of basal 24-hour urine free cortisol (UFC, serum cortisol after an overnight dexamethasone suppression test (DST, and serum cortisol and 24-hour UFC after low-dose DST and high-dose DST were all significantly lower in patients with SC compared with OC. Basal ACTH levels showed significantly higher in patients with SC compared with OC. The probability of recovering adrenal function during follow-up differed significantly between patients with OC and SC (P=0.001, with significant correlations with the degree of preoperative cortisol excess. Patients with OC required a longer duration of glucocorticoid replacement to recover a normal ACTH stimulation test compared with patients with SC (median 17.0 months vs. 4.0 months, P<0.001.ConclusionThe HPA axis recovery time after adrenalectomy in patients with SC is rapid and is dependent on the degree of cortisol excess. More precise definition of SC is necessary to achieve a better management of patients and to avoid the risk of under- or over-treatment of SC patients.

  18. Evidence against a critical role of CB1 receptors in adaptation of the hypothalamic-pituitary-adrenal axis and other consequences of daily repeated stress.

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    Rabasa, Cristina; Pastor-Ciurana, Jordi; Delgado-Morales, Raúl; Gómez-Román, Almudena; Carrasco, Javier; Gagliano, Humberto; García-Gutiérrez, María S; Manzanares, Jorge; Armario, Antonio

    2015-08-01

    There is evidence that endogenous cannabinoids (eCBs) play a role in the control of the hypothalamic-pituitary-adrenal (HPA) axis, although they appear to have dual, stimulatory and inhibitory, effects. Recent data in rats suggest that eCBs, acting through CB1 receptors (CB1R), may be involved in adaptation of the HPA axis to daily repeated stress. In the present study we analyze this issue in male mice and rats. Using a knock-out mice for the CB1 receptor (CB1-/-) we showed that mutant mice presented similar adrenocorticotropic hormone (ACTH) response to the first IMO as wild-type mice. Daily repeated exposure to 1h of immobilization reduced the ACTH response to the stressor, regardless of the genotype, demonstrating that adaptation occurred to the same extent in absence of CB1R. Prototypical changes observed after repeated stress such as enhanced corticotropin releasing factor (CRH) gene expression in the paraventricular nucleus of the hypothalamus, impaired body weight gain and reduced thymus weight were similarly observed in both genotypes. The lack of effect of CB1R in the expression of HPA adaptation to another similar stressor (restraint) was confirmed in wild-type CD1 mice by the lack of effect of the CB1R antagonist AM251 just before the last exposure to stress. Finally, the latter drug did not blunt the HPA, glucose and behavioral adaptation to daily repeated forced swim in rats. Thus, the present results indicate that CB1R is not critical for overall effects of daily repeated stress or proper adaptation of the HPA axis in mice and rats.

  19. FGF1 and FGF19 reverse diabetes by suppression of the hypothalamic-pituitary-adrenal axis.

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    Perry, Rachel J; Lee, Sangwon; Ma, Lie; Zhang, Dongyan; Schlessinger, Joseph; Shulman, Gerald I

    2015-04-28

    Fibroblast growth factor-1 (FGF1) and FGF19 have been shown to improve glucose metabolism in diabetic rodents, but how this occurs is unknown. Here to investigate the mechanism of action of these growth factors, we perform intracerebroventricular (i.c.v.) injections of recombinant FGF1 or FGF19 in an awake rat model of type 1 diabetes (T1D) and measure rates of whole-body lipolysis, hepatic acetyl CoA content, pyruvate carboxylase activity and hepatic glucose production. We show that i.c.v. injection of FGF19 or FGF1 leads to a ∼60% reduction in hepatic glucose production, hepatic acetyl CoA content and whole-body lipolysis, which results from decreases in plasma ACTH and corticosterone concentrations. These effects are abrogated by an intra-arterial infusion of corticosterone. Taken together these studies identify suppression of the HPA axis and ensuing reductions in hepatic acetyl CoA content as a common mechanism responsible for mediating the acute, insulin-independent, glucose-lowering effects of FGF1 and FGF19 in rodents with poorly controlled T1D.

  20. Ansiedade, pânico e o eixo hipotálamo-pituitária-adrenal Anxiety, panic and the hypothalamic-pituitary-adrenal axis

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    Frederico G Graeff

    2007-05-01

    Full Text Available OBJETIVO: Este artigo discute a ativação diferencial do eixo hipotálamo-pituitária-adrenal no transtorno de ansiedade generalizada e no transtorno de pânico. MÉTODO: Resultados de recentes revisões da literatura são resumidos e discutidos. RESULTADOS: Os resultados de estudos experimentais que dosaram o hormônio adrenocorticotrópico, o cortisol e a prolactina mostram que ataques de pânico naturais, bem como os provocados por agentes panicogênicos seletivos - como lactato de sódio e dióxido de carbono -, não ativam o eixo hipotálamo-pituitária-adrenal. Agonistas do receptor de colecistocinina do tipo B, como o peptídeo colecistocinina-4 e a pentagastrina, elevam os hormônios de estresse, independentemente da ocorrência de um ataque de pânico, parecendo ativar diretamente o eixo hipotálamo-pituitária-adrenal. O antagonista benzodiazepínico flumazenil não eleva o nível dos hormônios de estresse; porém, este agente farmacológico não induz ataques de pânico de modo consistente. Agentes farmacológicos que aumentam a ansiedade em pacientes de pânico (cafeína, ioimbina, agonistas serotonérgicos, assim como em pessoas saudáveis, elevam o nível dos hormônios de estresse. CONCLUSÕES: Além das diferenças na sintomatologia e na resposta farmacológica, o transtorno de ansiedade generalizada e o transtorno de pânico afetam os hormônios de estresse de modo distinto. Enquanto a ansiedade antecipatória e o transtorno de ansiedade generalizada ativam tanto o eixo hipotálamo-pituitária-adrenal como o simpático-adrenal, o ataque de pânico causa acentuada ativação simpática; porém, afeta pouco o eixo hipotálamo-pituitária-adrenal.OBJECTIVE: This article focuses on the differential activation of the hypothalamic-pituitary-adrenal axis in generalized anxiety disorder and panic disorder. METHOD: The results of recently reported reviews of the literature are summarized and discussed. RESULTS: The results of

  1. Blunted hypothalamic-pituitary-adrenal axis and insulin response to psychosocial stress in young adults born preterm at very low birth weight.

    Science.gov (United States)

    Kaseva, Nina; Wehkalampi, Karoliina; Pyhälä, Riikka; Moltchanova, Elena; Feldt, Kimmo; Pesonen, Anu-Katriina; Heinonen, Kati; Hovi, Petteri; Järvenpää, Anna-Liisa; Andersson, Sture; Eriksson, Johan G; Räikkönen, Katri; Kajantie, Eero

    2014-01-01

    Young adults born preterm at very low birth weight (VLBW, ≤1500 g) have higher levels of cardiovascular risk factors, including impaired glucose regulation, than their term-born peers. This could be mediated through altered hypothalamic-pituitary-adrenal axis (HPAA) response to stress. To compare HPAA, glucose and insulin responses provoked by psychosocial stress in VLBW subjects versus a comparison group of term-born controls. We studied 54 unimpaired young adults, aged 19-27 years, born at VLBW and a comparison group of 40 adults born at term, group-matched for age, sex and birth hospital, from one regional centre in southern Finland. The participants underwent a standardized psychosocial stress test (Trier Social Stress Test, TSST). In conjunction with TSST, we measured salivary cortisol, plasma ACTH, cortisol, glucose and insulin. Data were analysed with mixed-effects model and multiple linear regression analyses. Baseline concentrations for cortisol, ACTH, insulin and glucose were similar in VLBW and comparison groups. During TSST, analysed with mixed-effects model, overall concentrations of plasma cortisol were 17·2% lower (95% CI; 3·5 to 28·9) in the VLBW group. The VLBW group also had lower salivary (P = 0·04) and plasma cortisol (P = 0·02) responses to TSST. Insulin and glucose concentrations correlated with changes in cortisol concentrations. Accordingly, VLBW subjects had 26·5% lower increment in insulin (95% CI; 9·8-40·1). Analyses were adjusted for age, sex, body mass index, hormonal contraception, menstrual cycle phase, time of day and parental education. VLBW adults have lower HPAA responses to psychosocial stress than term-born controls. This is accompanied by a lower insulin response. © 2013 John Wiley & Sons Ltd.

  2. Short-term safety assessment of clobetasol propionate 0.05% shampoo: hypothalamic-pituitary-adrenal axis suppression, atrophogenicity, and ocular safety in subjects with scalp psoriasis.

    Science.gov (United States)

    Andres, Philippe; Poncet, Michel; Farzaneh, Sidou; Soto, Pascale

    2006-04-01

    Clobetasol propionate is known to be a very effective treatment for psoriasis; however, its use is limited by potent corticosteroid class related side effects such as hypothalamic-pituitary-adrenal (HPA) axis suppression and atrophogenicity. The aim of this single-center, parallel group, randomized study was to assess the HPA axis suppression potential, atrophogenicity, and ocular tolerability of clobetasol propionate shampoo in 26 patients with scalp psoriasis. Suitable subjects were treated once daily for 4 weeks with clobetasol propionate shampoo, to be rinsed off after 15 minutes or with a leave-on clobetasol propionate gel. The study demonstrated that clobetasol propionate shampoo did not lead to HPA axis suppression or to skin atrophy. Conversely, the gel led to HPA axis suppression and a decrease in skin thickness. Neither formulation had an impact on ocular safety. Despite the short contact application time, the clobetasol propionate shampoo provides similar efficacy results to the gel.

  3. Chlorella vulgaris reduces the impact of stress on hypothalamic-pituitary-adrenal axis and brain c-fos expression.

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    Souza Queiroz, Julia; Marín Blasco, Ignacio; Gagliano, Humberto; Daviu, Nuria; Gómez Román, Almudena; Belda, Xavier; Carrasco, Javier; Rocha, Michelle C; Palermo Neto, João; Armario, Antonio

    2016-03-01

    Predominantly emotional stressors activate a wide range of brain areas, as revealed by the expression of immediate early genes, such as c-fos. Chlorella vulgaris (CV) is considered a biological response modifier, as demonstrated by its protective activities against infections, tumors and stress. We evaluated the effect of acute pretreatment with CV on the peripheral and central responses to forced swimming stress in adult male rats. Pretreatment with CV produced a significant reduction of stress-related hypothalamic-pituitary-adrenal activation, demonstrated by decreased corticotrophin releasing factor gene expression in the hypothalamic paraventricular nucleus (PVN) and lower ACTH response. Hyperglycemia induced by the stressor was similarly reduced. This attenuated neuroendocrine response to stress occurred in parallel with a diminished c-fos expression in most evaluated areas, including the PVN. The data presented in this study reinforce the usefulness of CV to diminish the impact of stressors, by reducing the HPA response. Although our results suggest a central effect of CV, further studies are necessary to understand the precise mechanisms underpinning this effect.

  4. Fetal alcohol exposure alters proopiomelanocortin gene expression and hypothalamic-pituitary-adrenal axis function via increasing MeCP2 expression in the hypothalamus.

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    Omkaram Gangisetty

    Full Text Available Proopiomelanocortin (POMC is a precursor gene of the neuropeptide β-endorphin in the hypothalamus and is known to regulate various physiological functions including stress response. Several recent reports showed that fetal alcohol exposure programs the hypothalamus to produce lower levels of POMC gene transcripts and to elevate the hypothalamic-pituitary-adrenal (HPA axis response to stressful stimuli. We investigated the role of methyl CpG binding protein (MeCP2 in the effects of prenatal ethanol on POMC gene expression and hypothalamic-pituitary-adrenal (HPA axis function. Pregnant Sprague Dawley rats were fed between GD 7 and 21 with a liquid diet containing 6.7% alcohol, pair-fed with isocaloric liquid diet, or fed ad libitum with rat chow, and their male offsprings were used at 60 days after birth in this study. Fetal alcohol exposure reduced the level of POMC mRNA, but increased the level of DNA methylation of this gene in the arcuate nucleus (ARC of the hypothalamus where the POMC neuronal cell bodies are located. Fetal alcohol exposed rats showed a significant increase in MeCP2 protein levels in POMC cells, MeCP2 gene transcript levels as well as increased MeCP2 protein binding on the POMC promoter in the arcuate nucleus. Lentiviral delivery of MeCP2 shRNA into the third ventricle efficiently reduced MeCP2 expression and prevented the effect of prenatal ethanol on POMC gene expression in the arcuate nucleus. MeCP2-shRNA treatment also normalized the prenatal ethanol-induced increase in corticotropin releasing hormone (CRH gene expression in the hypothalamus and elevated plasma adrenocorticotrophic hormone (ACTH and corticosterone hormone responses to lipopolysaccharide (LPS challenge. These results suggest that fetal alcohol programming of POMC gene may involve recruitment of MeCP2 on to the methylated promoter of the POMC gene to suppress POMC transcript levels and contribute to HPA axis dysregulation.

  5. The involvement of noradrenergic mechanisms in the suppressive effects of diazepam on the hypothalamic-pituitary-adrenal axis activity in female rats

    Science.gov (United States)

    Švob Štrac, Dubravka; Muck-Šeler, Dorotea; Pivac, Nela

    2012-01-01

    Aim To elucidate the involvement of noradrenergic system in the mechanism by which diazepam suppresses basal hypothalamic-pituitary-adrenal (HPA) axis activity. Methods Plasma corticosterone and adrenocorticotropic hormone (ACTH) levels were determined in female rats treated with diazepam alone, as well as with diazepam in combination with clonidine (α2-adrenoreceptor agonist), yohimbine (α2-adrenoreceptor antagonist), alpha-methyl-p-tyrosine (α-MPT, an inhibitor of catecholamine synthesis), or reserpine (a catecholamine depleting drug) and yohimbine. Results Diazepam administered in a dose of 2.0 mg/kg suppressed basal HPA axis activity, ie, decreased plasma corticosterone and ACTH levels. Pretreatment with clonidine or yohimbine failed to affect basal plasma corticosterone and ACTH concentrations, but abolished diazepam-induced inhibition of the HPA axis activity. Pretreatment with α-MPT, or with a combination of reserpine and yohimbine, increased plasma corticosterone and ACTH levels and prevented diazepam-induced inhibition of the HPA axis activity. Conclusion The results suggest that α2-adrenoreceptors activity, as well as intact presynaptic noradrenergic function, are required for the suppressive effect of diazepam on the HPA axis activity. PMID:22661134

  6. Recovery by N-acetylcysteine from subchronic exposure to Imidacloprid-induced hypothalamic-pituitary-adrenal (HPA) axis tissues injury in male rats.

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    Annabi, Alya; Dhouib, Ines Bini; Lamine, Aicha Jrad; El Golli, Nargès; Gharbi, Najoua; El Fazâa, Saloua; Lasram, Mohamed Montassar

    2015-01-01

    Imidacloprid is the most important example of the neonicotinoid insecticides known to target the nicotinic acetylcholine receptor in insects, and potentially in mammals. N-Acetyl-l-cysteine (NAC) has been shown to possess curative effects in experimental and clinical investigations. The present study was designed to evaluate the recovery effect of NAC against Imidacloprid-induced oxidative stress and cholinergic transmission alteration in hypothalamic-pituitary-adrenal (HPA) axis of male rats following subchronic exposure. About 40 mg/kg of Imidacloprid was administered daily by intragastric intubation and 28 days later, the rats were sacrificed and HPA axis tissues were removed for different analyses. Imidacloprid increased adrenal relative weight and cholesterol level indicating an adaptive stage of the general alarm reaction to stress. Moreover, Imidacloprid caused a significant increase in malondialdehyde level, the antioxidants catalase, superoxide dismutase and glutathione-S-transferase showed various alterations following administration and significant depleted thiols content was only recorded in hypothalamic tissue. Furthermore, the hypothalamic and pituitary acetylcholinesterase activity and calcium level were significantly increased highlighting the alteration of cholinergic activity. The present findings revealed that HPA axis is a sensitive target to Imidacloprid (IMI). Interestingly, the use of NAC for only 7 days post-exposure to IMI showed a partial therapeutic effect against Imidacloprid toxicity.

  7. Positive environmental modification of depressive phenotype and abnormal hypothalamic-pituitary-adrenal axis activity in female C57BL/6J mice during abstinence from chronic ethanol consumption

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    Terence Y Pang

    2013-07-01

    Full Text Available Depression is a commonly reported co-morbidity during rehabilitation from alcohol use disorders and its presence is associated with an increased likelihood of relapse. Interventions which impede the development of depression could be of potential benefit if incorporated into treatment programs. We previously demonstrated an ameliorative effect of physical exercise on depressive behaviours in a mouse model of alcohol abstinence. Here, we show that environmental enrichment (cognitive and social stimulation has a similar beneficial effect. The hypothalamic-pituitary-adrenal (HPA axis is a key physiological system regulating stress responses and its dysregulation has been separably implicated in the pathophysiology of depression and addiction disorders. We performed a series of dexamethasone challenges and found that mice undergoing 2 weeks of alcohol abstinence had significantly greater corticosterone and ACTH levels following a DEX-CRH challenge compared to water controls. Environmental enrichment during alcohol abstinence corrected the abnormal DEX-CRH corticosterone response despite a further elevation of ACTH levels. Examination of gene expression revealed abstinence-associated alterations in glucocorticoid receptor (Gr, corticotrophin releasing hormone (Crh and pro-opiomelanocortin (Pomc1 mRNA levels which were differentially modulated by environmental enrichment. Overall, our study demonstrates a benefit of environmental enrichment on alcohol abstinence-associated depressive behaviours and HPA axis dysregulation.

  8. Exploration of the Hypothalamic-Pituitary-Adrenal Axis to Improve Animal Welfare by Means of Genetic Selection: Lessons from the South African Merino.

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    Hough, Denise; Swart, Pieter; Cloete, Schalk

    2013-05-17

    It is a difficult task to improve animal production by means of genetic selection, if the environment does not allow full expression of the animal's genetic potential. This concept may well be the future for animal welfare, because it highlights the need to incorporate traits related to production and robustness, simultaneously, to reach sustainable breeding goals. This review explores the identification of potential genetic markers for robustness within the hypothalamic-pituitary-adrenal axis (HPAA), since this axis plays a vital role in the stress response. If genetic selection for superior HPAA responses to stress is possible, then it ought to be possible to breed robust and easily managed genotypes that might be able to adapt to a wide range of environmental conditions whilst expressing a high production potential. This approach is explored in this review by means of lessons learnt from research on Merino sheep, which were divergently selected for their multiple rearing ability. These two selection lines have shown marked differences in reproduction, production and welfare, which makes this breeding programme ideal to investigate potential genetic markers of robustness. The HPAA function is explored in detail to elucidate where such genetic markers are likely to be found.

  9. Exploration of the Hypothalamic-Pituitary-Adrenal Axis to Improve Animal Welfare by Means of Genetic Selection: Lessons from the South African Merino

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    Schalk Cloete

    2013-05-01

    Full Text Available It is a difficult task to improve animal production by means of genetic selection, if the environment does not allow full expression of the animal’s genetic potential. This concept may well be the future for animal welfare, because it highlights the need to incorporate traits related to production and robustness, simultaneously, to reach sustainable breeding goals. This review explores the identification of potential genetic markers for robustness within the hypothalamic-pituitary-adrenal axis (HPAA, since this axis plays a vital role in the stress response. If genetic selection for superior HPAA responses to stress is possible, then it ought to be possible to breed robust and easily managed genotypes that might be able to adapt to a wide range of environmental conditions whilst expressing a high production potential. This approach is explored in this review by means of lessons learnt from research on Merino sheep, which were divergently selected for their multiple rearing ability. These two selection lines have shown marked differences in reproduction, production and welfare, which makes this breeding programme ideal to investigate potential genetic markers of robustness. The HPAA function is explored in detail to elucidate where such genetic markers are likely to be found.

  10. A Fall in Plasma Free Fatty Acid (FFA) Level Activates the Hypothalamic-Pituitary-Adrenal Axis Independent of Plasma Glucose: Evidence for Brain Sensing of Circulating FFA

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    Oh, Young Taek; Oh, Ki-Sook; Kang, Insug

    2012-01-01

    The brain responds to a fall in blood glucose by activating neuroendocrine mechanisms for its restoration. It is unclear whether the brain also responds to a fall in plasma free fatty acids (FFA) to activate mechanisms for its restoration. We examined whether lowering plasma FFA increases plasma corticosterone or catecholamine levels and, if so, whether the brain is involved in these responses. Plasma FFA levels were lowered in rats with three independent antilipolytic agents: nicotinic acid (NA), insulin, and the A1 adenosine receptor agonist SDZ WAG 994 with plasma glucose clamped at basal levels. Lowering plasma FFA with these agents all increased plasma corticosterone, but not catecholamine, within 1 h, accompanied by increases in plasma ACTH. These increases in ACTH or corticosterone were abolished when falls in plasma FFA were prevented by Intralipid during NA or insulin infusion. In addition, the NA-induced increases in plasma ACTH were completely prevented by administration of SSR149415, an arginine vasopressin receptor antagonist, demonstrating that the hypothalamus is involved in these responses. Taken together, the present data suggest that the brain may sense a fall in plasma FFA levels and activate the hypothalamic-pituitary-adrenal axis to increase plasma ACTH and corticosterone, which would help restore FFA levels. Thus, the brain may be involved in the sensing and control of circulating FFA levels. PMID:22669895

  11. Acupuncture Relieves the Excessive Excitation of Hypothalamic-Pituitary-Adrenal Cortex Axis Function and Correlates with the Regulatory Mechanism of GR, CRH, and ACTHR

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    Shao-Jun Wang

    2014-01-01

    Full Text Available It had been indicated in the previous studies that acupuncture relieved the excessive excitation of hypothalamic-pituitary-adrenal cortex axis (HPAA function induced by stress stimulation. But the changes in glucocorticoid receptor (GR induced by acupuncture have not been detected clearly. The objective of the study was to observe the impacts of acupuncture on the protein expressions of corticotrophin releasing hormone (CRH, adrenocorticotropic hormone receptor (ACTHR, and GR under the physiological and stress states. The results showed that under the stress state, acupuncture upregulated the protein expression of GR in the hippocampus, hypothalamic paraventricular nucleus (PVN, and pituitary gland, downregulated the protein expression of GR in the adrenal cortex, and obviously reduced the protein expressions of CRH and ACTHR. Under the physiological state, acupuncture promoted GR protein expression in the hippocampus and CRH protein expression in the hippocampus and PVN. The results explained that acupuncture regulated the stress reaction via promoting the combination of glucocorticoids (GC with GR, and GR protein expression. The increase of GR protein expression induced feedback inhibition on the overexpression of CRH and ACTHR, likely decreased GC level, and caused the reduction of GR protein expression in the adrenal cortex.

  12. Acupuncture Relieves the Excessive Excitation of Hypothalamic-Pituitary-Adrenal Cortex Axis Function and Correlates with the Regulatory Mechanism of GR, CRH, and ACTHR

    Science.gov (United States)

    Wang, Shao-Jun; Zhang, Jiao-Jiao; Qie, Li-Li

    2014-01-01

    It had been indicated in the previous studies that acupuncture relieved the excessive excitation of hypothalamic-pituitary-adrenal cortex axis (HPAA) function induced by stress stimulation. But the changes in glucocorticoid receptor (GR) induced by acupuncture have not been detected clearly. The objective of the study was to observe the impacts of acupuncture on the protein expressions of corticotrophin releasing hormone (CRH), adrenocorticotropic hormone receptor (ACTHR), and GR under the physiological and stress states. The results showed that under the stress state, acupuncture upregulated the protein expression of GR in the hippocampus, hypothalamic paraventricular nucleus (PVN), and pituitary gland, downregulated the protein expression of GR in the adrenal cortex, and obviously reduced the protein expressions of CRH and ACTHR. Under the physiological state, acupuncture promoted GR protein expression in the hippocampus and CRH protein expression in the hippocampus and PVN. The results explained that acupuncture regulated the stress reaction via promoting the combination of glucocorticoids (GC) with GR, and GR protein expression. The increase of GR protein expression induced feedback inhibition on the overexpression of CRH and ACTHR, likely decreased GC level, and caused the reduction of GR protein expression in the adrenal cortex. PMID:24761151

  13. Acupuncture Relieves the Excessive Excitation of Hypothalamic-Pituitary-Adrenal Cortex Axis Function and Correlates with the Regulatory Mechanism of GR, CRH, and ACTHR.

    Science.gov (United States)

    Wang, Shao-Jun; Zhang, Jiao-Jiao; Qie, Li-Li

    2014-01-01

    It had been indicated in the previous studies that acupuncture relieved the excessive excitation of hypothalamic-pituitary-adrenal cortex axis (HPAA) function induced by stress stimulation. But the changes in glucocorticoid receptor (GR) induced by acupuncture have not been detected clearly. The objective of the study was to observe the impacts of acupuncture on the protein expressions of corticotrophin releasing hormone (CRH), adrenocorticotropic hormone receptor (ACTHR), and GR under the physiological and stress states. The results showed that under the stress state, acupuncture upregulated the protein expression of GR in the hippocampus, hypothalamic paraventricular nucleus (PVN), and pituitary gland, downregulated the protein expression of GR in the adrenal cortex, and obviously reduced the protein expressions of CRH and ACTHR. Under the physiological state, acupuncture promoted GR protein expression in the hippocampus and CRH protein expression in the hippocampus and PVN. The results explained that acupuncture regulated the stress reaction via promoting the combination of glucocorticoids (GC) with GR, and GR protein expression. The increase of GR protein expression induced feedback inhibition on the overexpression of CRH and ACTHR, likely decreased GC level, and caused the reduction of GR protein expression in the adrenal cortex.

  14. Can variation in hypothalamic-pituitary-adrenal (HPA-axis activity explain the relationship between depression and cognition in bipolar patients?

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    Marieke J van der Werf-Eldering

    Full Text Available BACKGROUND: Dysregulation of the hypothalamic-pituitary-adrenal (HPA axis is thought to be associated with more mood symptoms and worse cognitive functioning. This study examined whether variation in HPA axis activity underlies the association between mood symptoms and cognitive functioning. METHODOLOGY/PRINCIPAL FINDINGS: In 65 bipolar patients cognitive functioning was measured in domains of psychomotor speed, speed of information processing, attentional switching, verbal memory, visual memory, executive functioning and an overall mean score. Severity of depression was assessed by the Inventory of Depressive Symptomatology-self rating version. Saliva cortisol measurements were performed to calculate HPA axis indicators: cortisol awakening response, diurnal slope, the evening cortisol level and the cortisol suppression on the dexamethasone suppression test. Regression analyses of depressive symptoms and cognitive functioning on each HPA axis indicator were performed. In addition we calculated percentages explanation of the association between depressive symptoms and cognition by HPA axis indicators. Depressive symptoms were associated with dysfunction in psychomotor speed, attentional switching and the mean score, as well as with attenuation in diurnal slope value. No association was found between HPA axis activity and cognitive functioning and HPA axis activity did not explain the associations between depressive symptoms and cognition. CONCLUSIONS/SIGNIFICANCE: As our study is the first one in this field specific for bipolar patients and changes in HPA-axis activity did not seem to explain the association between severity of depressive symptoms and cognitive functioning in bipolar patients, future studies are needed to evaluate other factors that might explain this relationship.

  15. Sex differences in early-life programming of the hypothalamic-pituitary-adrenal axis in humans suggest increased vulnerability in females: a systematic review.

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    Carpenter, T; Grecian, S M; Reynolds, R M

    2017-04-01

    Fetal glucocorticoid overexposure is a key mechanism linking early development with later-life disease. In humans, low birth weight associates with increased fasting cortisol, hypothalamic-pituitary-adrenal (HPA) axis reactivity, and with cardiovascular risk and cognitive decline. As there are sex differences in these adult diseases, we hypothesized that there may be sex differences in programming of the HPA axis in response to prenatal stressors. We conducted a systematic review following Meta-Analysis of Observational Studies in Epidemiology and Preferred Reporting Items for Systematic Reviews and Meta-Analysis. We searched Embase, MEDLINE and Web of Science from inception to 31 October 2016. We included studies related to sex differences, prenatal exposures and HPA axis. We excluded studies investigating specific disease states. The 23 included studies investigated the consequences of low birth weight, preterm birth and maternal stressors of asthma, psychosocial stress and glucocorticoid medications on HPA axis outcomes of placental glucocorticoid biology and offspring HPA axis function in early life and later life. Female offspring exposed to stressors had increased HPA axis reactivity compared with males. Furthermore, the female placenta increased its permeability to maternal glucocorticoids following maternal stress with changes in the expression of 11β-hydroxysteroid dehydrogenase enzymes in response to maternal glucocorticoid exposure or asthma. Among males there was some evidence of altered diurnal cortisol secretion. We conclude that although there is some evidence of male vulnerability leading to altered diurnal cortisol secretion, the female HPA axis is more vulnerable to programming, particularly in terms of its reactivity; this suggests a mechanism underlying sex differences in later-life diseases.

  16. Immediate and prolonged effects of alcohol exposure on the activity of the hypothalamic-pituitary-adrenal axis in adult and adolescent rats

    Science.gov (United States)

    ALLEN, Camryn D.; LEE, Soon; KOOB, George F.; RIVIER, Catherine

    2011-01-01

    Alcohol stimulates the hypothalamic-pituitary-adrenal (HPA) axis. Part of this influence is likely exerted directly at the level of the corticotropin-releasing factor (CRF) gene, but intermediates may also play a role. Here we review the effect of alcohol on this axis, provide new data on the effects of binge drinking during adolescence, and argue for a role of catecholaminergic circuits. Indeed, acute injection of this drug activates brain stem adrenergic and noradrenergic circuits, and their lesion, or blockade of α1 adrenergic receptors significantly blunts alcohol-induced ACTH release. As alcohol can influence the HPA axis even once discontinued, and alcohol consumption in young people is associated with increased adult drug abuse (a phenomenon possibly mediated by the HPA axis), we determined whether alcohol consumption during adolescence modified this axis. The number of CRF-immunoreactive (ir) cells/section was significantly decreased in the central nucleus of the amygdala of adolescent self-administering binge-drinking animals, compared to controls. When another group of adolescent binge-drinking rats was administered alcohol in adulthood, the number of colocalized c-fos-ir and PNMT-ir cells/brain stem section in the C3 area was significantly decreased, compared to controls. As the HPA axis response to alcohol is blunted in adult rats exposed to alcohol vapors during adolescence, a phenomenon which was not observed in our model of self-administration, it is possible that the blood alcohol levels achieved in various models play a role in the long-term consequences of exposure to alcohol early in life. Collectively, these results suggest an important role of brain catecholamines in modulating the short- and long-term consequences of alcohol administration. PMID:21300146

  17. Multi-Level Risk Factors for Suicidal Ideation Among at-Risk Adolescent Females: The Role of Hypothalamic-Pituitary-Adrenal Axis Responses to Stress.

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    Giletta, Matteo; Calhoun, Casey D; Hastings, Paul D; Rudolph, Karen D; Nock, Matthew K; Prinstein, Mitchell J

    2015-07-01

    Adopting a multi-level approach, this study examined risk factors for adolescent suicidal ideation, with specific attention to (a) hypothalamic-pituitary-adrenal (HPA) axis stress responses and (b) the interplay between HPA-axis and other risk factors from multiple domains (i.e., psychological, interpersonal and biological). Participants were 138 adolescent females (M(age) = 14.13 years, SD = 1.40) at risk for suicidal behaviors. At baseline, lifetime suicidal ideation and a number of risk factors were assessed (i.e., depressive symptoms, impulsiveness, pubertal status and peer stress). Participants were exposed to a psychosocial stress task and HPA-axis responses were assessed by measuring cortisol levels pre- and post-stressor. At 3 months post-baseline, suicidal ideation again was assessed. Using group-based trajectory modeling, three groups of cortisol stress-response patterns were identified (i.e., hyporesponsive, normative, and hyperresponsive). As compared to females in the normative and hyporesponsive group, females in the hyperresponsive group were more likely to report a lifetime history of suicidal ideation at baseline, above and beyond the effects of the other predictors. Moreover, as compared to females in the normative group, females in the hyperresponsive group were at increased risk for reporting suicidal ideation 3 months later, after controlling for prior ideation. No interactions between cortisol group and the other risk factors were significant, with the exception of a non-significant trend between impulsiveness and cortisol group on lifetime suicidal ideation. Findings highlight the importance of HPA-axis responses to acute stressors as a risk factor for suicidal ideation among adolescents.

  18. Early life stress in depressive patients: role of glucocorticoid and mineralocorticoid receptors and of hypothalamic-pituitary-adrenal axis activity.

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    Juruena, Mario Francisco; Werne Baes, Cristiane Von; Menezes, Itiana Castro; Graeff, Frederico Guilherme

    2015-01-01

    Depression is a chronic, recurrent and long-term disorder characterized by high rates of impairment and several comorbidities. Early life stress (ELS) is associated with the increased risk for developing depression in adulthood, influences its clinical course and predicts a poorer treatment outcome. Stressful life events play an important role in the pathogenesis of depression, being well established as acute triggers of psychiatric illness. The vulnerability for developing depression is associated to changes in neurobiological systems related to stress regulation. The hypothalamic-pituitaryadrenal (HPA) axis responds to external and internal stimuli. Reported results indicate that stress in early phases of development can induce persistent changes in the response of the HPA axis to stress in adulthood, leading to a raised susceptibility to depression. These abnormalities appear to be related to the HPA axis deregulation in depression, partially due to an imbalance between glucocorticoid receptors (GR) and mineral ocorticoid receptors (MR). While most studies have consistently demonstrated that GR function is impaired in major depression (reduced GR-mediated feedback in HPA axis), data about the MR role in depression are still limited and contr oversial. Thus, in this review article we summarize the main reported findings about the consequences of ELS in HPA axis functioning and in the responsivity of MR/GR receptors in depression.

  19. Cortisol reactivity and suicidal behavior: Investigating the role of hypothalamic-pituitary-adrenal axis responses to stress in suicide attempters and ideators.

    Science.gov (United States)

    O'Connor, Daryl B; Green, Jessica A; Ferguson, Eamonn; O'Carroll, Ronan E; O'Connor, Rory C

    2017-01-01

    Every 40s a person dies by suicide somewhere in the world. The causes of suicidal behavior are not fully understood. Dysregulated hypothalamic-pituitary-adrenal (HPA) axis activity, as measured by cortisol levels, is one potential risk factor. The current study aimed to investigate whether cortisol reactivity to a laboratory stress task differentiated individuals who had previously made a suicide attempt from those who had thought about suicide (suicide ideators) and control participants. One hundred and sixty participants were recruited to a previous attempt, a suicidal ideation or a control group. Participants completed background questionnaires before completing the Maastricht Acute Stress Test (MAST). Cortisol levels were assessed throughout the stress task. Measures of suicide behavior were measured at baseline, 1 month and 6 month follow-up. Participants who had made a previous suicide attempt exhibited significantly lower aggregate cortisol levels during the MAST compared to participants in the control group; suicide ideators were intermediate to both groups. This effect, however, was driven by participants who made an attempt within the past year, and to some degree by those with a family history of attempt. Participants who made a suicide attempt and had a family history of suicide exhibited the lowest levels of cortisol in response to stress. Finally, lower levels of cortisol in response to the MAST were associated with higher levels of suicidal ideation at 1-month follow-up in the suicide attempter group. These results are consistent with other findings indicating that blunted HPA axis activity is associated with some forms of suicidal behavior. The challenge for researchers is to elucidate the precise causal mechanisms linking stress, cortisol and suicide risk.

  20. Effect of continuous positive airway pressure therapy on hypothalamic-pituitary-adrenal axis function and 24-h blood pressure profile in obese men with obstructive sleep apnea syndrome.

    Science.gov (United States)

    Carneiro, Gláucia; Togeiro, Sônia Maria; Hayashi, Lílian F; Ribeiro-Filho, Fernando Flexa; Ribeiro, Artur Beltrame; Tufik, Sérgio; Zanella, Maria Teresa

    2008-08-01

    Obstructive sleep apnea syndrome (OSAS) increases the risk of cardiovascular events. Sympathetic nervous system and hypothalamic-pituitary-adrenal (HPA) axis activation may be the mechanism of this relationship. The aim of this study was to evaluate HPA axis and ambulatory blood pressure monitoring in obese men with and without OSAS and to determine whether nasal continuous positive airway pressure therapy (nCPAP) influenced responses. Twenty-four-hour ambulatory blood pressure monitoring and overnight cortisol suppression test with 0.25 mg of dexamethasone were performed in 16 obese men with OSAS and 13 obese men controls. Nine men with severe apnea were reevaluated 3 mo after nCPAP therapy. Body mass index and blood pressure of OSAS patients and obese controls were similar. In OSAS patients, the percentage of fall in systolic blood pressure at night (P = 0.027) and salivary cortisol suppression postdexamethasone (P = 0.038) were lower, whereas heart rate (P = 0.022) was higher compared with obese controls. After nCPAP therapy, patients showed a reduction in heart rate (P = 0.036) and a greater cortisol suppression after dexamethasone (P = 0.001). No difference in arterial blood pressure (P = 0.183) was observed after 3 mo of nCPAP therapy. Improvement in cortisol suppression was positively correlated with an improvement in apnea-hypopnea index during nCPAP therapy (r = 0.799, P = 0.010). In conclusion, men with OSAS present increased postdexamethasone cortisol levels and heart rate, which were recovered by nCPAP.

  1. Highly Palatable Food during Adolescence Improves Anxiety-Like Behaviors and Hypothalamic-Pituitary-Adrenal Axis Dysfunction in Rats that Experienced Neonatal Maternal Separation

    Directory of Open Access Journals (Sweden)

    Jong-Ho Lee

    2014-06-01

    Full Text Available BackgroundThis study was conducted to examine the effects of ad libitum consumption of highly palatable food (HPF during adolescence on the adverse behavioral outcome of neonatal maternal separation.MethodsMale Sprague-Dawley pups were separated from dam for 3 hours daily during the first 2 weeks of birth (maternal separation, MS or left undisturbed (nonhandled, NH. Half of MS pups received free access to chocolate cookies in addition to ad libitum chow from postnatal day 28 (MS+HPF. Pups were subjected to behavioral tests during young adulthood. The plasma corticosterone response to stress challenge was analyzed by radioimmunoassay.ResultsDaily caloric intake and body weight gain did not differ among the experimental groups. Ambulatory activities were decreased defecation activity and rostral grooming were increased in MS controls (fed with chow only compared with NH rats. MS controls spent less time in open arms, and more time in closed arms during the elevated plus maze test, than NH rats. Immobility duration during the forced swim test was increased in MS controls compared with NH rats. Cookie access normalized the behavioral scores of ambulatory and defecation activities and grooming, but not the scores during the elevated plus maze and swim tests in MS rats. Stress-induced corticosterone increase was blunted in MS rats fed with chow only, and cookie access normalized it.ConclusionProlonged access to HPF during adolescence and youth partly improves anxiety-related, but not depressive, symptoms in rats that experienced neonatal maternal separation, possibly in relation with improved function of the hypothalamic-pituitary-adrenal (HPA axis.

  2. Sex-specific prediction of hypothalamic-pituitary-adrenal axis activity by pituitary volume during adolescence: a longitudinal study from 12 to 17 years of age.

    Science.gov (United States)

    Kaess, Michael; Simmons, Julian G; Whittle, Sarah; Jovev, Martina; Chanen, Andrew M; Yücel, Murat; Pantelis, Christos; Allen, Nicholas B

    2013-11-01

    To investigate the longitudinal relationship between pituitary gland volume (PGV) and parameters of hypothalamic-pituitary-adrenal axis (HPAA) functioning during adolescence. Participants were 49 adolescents (19 girls and 30 boys) selected from a larger longitudinal, population-based study of adolescent development. Assessments were conducted at three time points (S1, S2 and S3). MRI sessions were at S1 (age: M=12.62, SD=0.45 years) and S3 (M=16.48, SD=0.53 years) and multiple assessments of salivary cortisol were undertaken at S2 (M=15.51, SD=0.35 years). PGV was measured via previously validated manual tracing methods, and the cortisol awakening response (CAR) and diurnal slope (DSL) were used as indices of HPAA functioning. A significant sex-linked interaction was found for PGV at S1 predicting both CAR (p=0.025) and DSL (p=0.009) at S2. Specifically, PGV at S1 significantly predicted CAR (p=0.033) and DSL (p=0.010) in boys only, with no significant results found for girls. Neither CAR nor DSL at S2 predicted growth of PGV from S1 to S3. PGV in early adolescence predicted HPAA functioning in mid-adolescent boys but not in girls. The results suggest a significant influence of sex-specific development on the relationship between PGV and HPAA activity and reactivity. The findings have potential implications for understanding and interpreting sex-linked and stress related clinical disorders that emerge during mid-to-late adolescence. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Chronic stress adaptation of the nitric oxide synthases and IL-1β levels in brain structures and hypothalamic-pituitary-adrenal axis activity induced by homotypic stress.

    Science.gov (United States)

    Gadek-Michalska, A; Tadeusz, J; Rachwalska, P; Bugajski, J

    2015-06-01

    β level in response to homotypic stress after 3 days and after 14 days. The present results indicate time-related similarities in the potent alterations in IL-1β and iNOS protein levels in brain structures. Single restraint induced a significant increase of plasma IL-1β level which was abolished by pretreatment with IL-1 receptor antagonist (IL-1Ra). A parallel strong increase of plasma ACTH and corticosterone levels were significantly impaired by IL-1Ra suggesting a marked involvement of stress-induced stimulation of ACTH and corticosterone by IL-1β in single restraint. In repeatedly restrained rats IL-1Ra significantly blunted plasma IL-1β level induced by homotypic stress. A parallel strong increase in plasma ACTH level by homotypic stress was not substantially altered by pretreatment with IL-1Ra in repeatedly stressed rats. Plasma a corticosterone level increased by homotypic stress in rats restrained for 3 and 14 days was not affected by pretreatment with IL-1Ra, but after for 7 days its level was significantly enhanced. These results suggest that repeated stress desensitizes IL-1β-induced stimulatory component in a single restraint stress-induced hypothalamic-pituitary-adrenal (HPA) axis stimulation. A sensitization by homotypic stress of corticosterone response after restraint for 7 days may depend on other stimulatory systems acting within adrenal glands during prolonged stress. Comparative data from the same model of rather mild psychological stress allows for the comparison of functional adaptive changes of NO synthases and IL-1β in brain structures involved in stress regulation. In general, the iNOS system is strongly sensitized by repeated stress for 3 days in prefrontal cortex and hippocampus. Increased plasma IL-1β level by a single restraint stress is significantly involved in ACTH and corticosterone secretion. Repeated stress for 3-14 days reduces this participation of IL-1β in pituitary-adrenal stimulation.

  4. The Environmental Pollutant Tributyltin Chloride Disrupts the Hypothalamic-Pituitary-Adrenal Axis at Different Levels in Female Rats.

    Science.gov (United States)

    Merlo, Eduardo; Podratz, Priscila L; Sena, Gabriela C; de Araújo, Julia F P; Lima, Leandro C F; Alves, Izabela S S; Gama-de-Souza, Letícia N; Pelição, Renan; Rodrigues, Lívia C M; Brandão, Poliane A A; Carneiro, Maria T W D; Pires, Rita G W; Martins-Silva, Cristina; Alarcon, Tamara A; Miranda-Alves, Leandro; Silva, Ian V; Graceli, Jones B

    2016-08-01

    Tributyltin chloride (TBT) is an environmental contaminant that is used as a biocide in antifouling paints. TBT has been shown to induce endocrine-disrupting effects. However, studies evaluating the effects of TBT on the hypothalamus-pituitary-adrenal (HPA) axis are especially rare. The current study demonstrates that exposure to TBT is critically responsible for the improper function of the mammalian HPA axis as well as the development of abnormal morphophysiology in the pituitary and adrenal glands. Female rats were treated with TBT, and their HPA axis morphophysiology was assessed. High CRH and low ACTH expression and high plasma corticosterone levels were detected in TBT rats. In addition, TBT leads to an increased in the inducible nitric oxide synthase protein expression in the hypothalamus of TBT rats. Morphophysiological abnormalities, including increases in inflammation, a disrupted cellular redox balance, apoptosis, and collagen deposition in the pituitary and adrenal glands, were observed in TBT rats. Increases in adiposity and peroxisome proliferator-activated receptor-γ protein expression in the adrenal gland were observed in TBT rats. Together, these data provide in vivo evidence that TBT leads to functional dissociation between CRH, ACTH, and costicosterone, which could be associated an inflammation and increased of inducible nitric oxide synthase expression in hypothalamus. Thus, TBT exerts toxic effects at different levels on the HPA axis function.

  5. Effects of atrazine (ATR), deisopropylatrazine (DIA), Diaminochlorotriazine (DACT) on the hypothalamic-pituitary-adrenal (HPA) axis in female rats

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    We previously reported that a single dose of the herbicide ATR stimulated the HPA axis in the male rat while equimolar doses of its primary metabolite, DACT, had a minimal effect. In this study, we evaluated the effects of one or four daily doses of ATR, DACT, and an intermediat...

  6. EFFECTS OF ATRAZINE (ATR), DEISOPROPYLATRAZINE (DIA), AND DIAMINOCHLOROTRIAZINE (DACT) ON THE HYPOTHALAMIC-PITUITARY-ADRENAL (HPA) AXIS IN FEMALE RATS

    Science.gov (United States)

    Previously we reported that a single dose of ATR herbicide stimulated HPA axis activation in the male rat while its primary metabolite, DACT, did so to a lesser extent. In this study, we evaluated the effects of ATR, DACT, and an intermediate metabolite, DIA, on adrenocorticotrop...

  7. [Effects of blockage of hypothalamic-pituitary-adrenal cortex axis by metyrapone and Jiawei Xiaoyao Pills on immune system in mice exposed to chronic emotional stress].

    Science.gov (United States)

    Zhang, Yun; Wu, Zhen-Yu; Xiao, Jian; Geng, Xiao-Feng; Guo, Yan-Xia; Li, Shi-Jie

    2006-07-01

    To explore the effects of Jiawei Xiaoyao Pills (JWXYP) on immune system of mice exposed to chronic emotional stress, and to compare its effects with blockage of hypothalamic-pituitary-adrenal cortex axis (HPAA) by metyrapone. Eighty male mice were randomly divided into eight groups: normal saline-treated group, normal saline-treated stress group, JWXYP-treated group, JWXYP-treated stress group, metyrapone-treated group, metyrapone-treated stress group, metyrapone and JWXYP-treated group and metyrapone and JWXYP-treated stress group. A box of electrical shock was used to induce chronic emotional stress in mice. The metyrapone was applied to blocking the HPAA. The JWXYP, a classical formula of traditional Chinese medicine, which can alleviate the damages caused by chronic emotional stress, was also used to compare its effects with that of metyrapone. The body weight, thymus index, rate of apoptosis in thymus, serum concentration of glucocorticoid, activity of natural killer cells, lymphocyte transmission rate of mice were all measured and examined after interventions. The pathological changes of thymus tissue were observed. The thymus index, activity of natural killer cells and lymphocyte transmission rate were lower while the rate of apoptosis in thymus as well as the severity degree of pathological damages in thymus tissue were increased in the different drug-treated stress groups as compared with those in the corresponding drug-treated groups without stress. The activity of natural killer cells and the lymphocyte transmission rate induced by lipopolysaccharide were increased while the serum concentration of glucocorticoid and the severity degree of pathological damages in thymus tissue were decreased in both the metyrapone-treated stress group and JWXYP-treated stress group as compared with those in the normal saline-treated stress group. The combined intervention of metyrapone and JWXYP did not show better effects on immune system in mice exposed to chronic

  8. Sleep restriction alters the hypothalamic-pituitary-adrenal response to stress

    NARCIS (Netherlands)

    Meerlo, P; Koehl, M; van der Borght, K; Turek, FW

    2002-01-01

    Chronic sleep restriction is an increasing problem in many countries and may have many, as yet unknown, consequences for health and well being. Studies in both humans and rats suggest that sleep deprivation may activate the hypothalamic-pituitary-adrenal (HPA) axis, one of the main neuroendocrine

  9. Sleep restriction alters the hypothalamic-pituitary-adrenal response to stress

    NARCIS (Netherlands)

    Meerlo, P; Koehl, M; van der Borght, K; Turek, FW

    2002-01-01

    Chronic sleep restriction is an increasing problem in many countries and may have many, as yet unknown, consequences for health and well being. Studies in both humans and rats suggest that sleep deprivation may activate the hypothalamic-pituitary-adrenal (HPA) axis, one of the main neuroendocrine st

  10. Hair-Normalized Cortisol Waking Response as a Novel Biomarker of Hypothalamic-Pituitary-Adrenal Axis Activity following Acute Trauma: A Proof-of-Concept Study with Pilot Results

    Directory of Open Access Journals (Sweden)

    David M. Walton

    2013-01-01

    Full Text Available The mechanisms underlying the development of persistent posttraumatic pain and disability remain elusive. Recent evidence suggests that disordered stress-system pathway (hypothalamic-pituitary-adrenal axis activity may be responsible for the genesis and maintenance of long-term sensory and emotional problems. However, confidence in current evidence is limited by the necessarily retrospective collection of data. Hair cortisol can serve as a calendar of HPA axis activity going back several months prior to injury. The purposes of this pilot study were to determine the feasibility of using hair cortisol and hair-normalized salivary cortisol as biomarkers of distress following traumatic injuries of whiplash or distal radius fracture. Ten subjects provided complete data within 3 weeks of injury. Hair cortisol, cortisol waking response (CWR, and mean daily cortisol (MDC were captured at inception, as were self-report indicators of pain, disability, and pain catastrophizing. Pain and disability were also captured 3 months after injury. Results indicate that cortisol waking response may be a useful biomarker of current distress as measured using the pain catastrophizing scale, especially when normalized to 3-month hair cortisol (r=0.77 raw, 0.93 normalized. Hair-normalized CWR may also have predictive capacity, correlating with 3-month self-reported disability at r=0.70. While promising, the results must be viewed in light of the small sample.

  11. Enhancement of BDNF Concentration and Restoration of the Hypothalamic-Pituitary-Adrenal Axis Accompany Reduced Depressive-Like Behaviour in Stressed Ovariectomised Rats Treated with Either Tualang Honey or Estrogen

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    Badriya Al-Rahbi

    2014-01-01

    Full Text Available A possible interaction between glucocorticoids and estrogen-induced increases in brain-derived-neurotrophic factor (BDNF expression in enhancing depressive-like behaviour has been documented. Here we evaluated the effects of Tualang honey, a phytoestrogen, and 17β-estradiol (E2 on the depressive-like behaviour, stress hormones, and BDNF concentration in stressed ovariectomised (OVX rats. The animals were divided into six groups: (i nonstressed sham-operated control, (ii stressed sham-operated control, (iii nonstressed OVX, (iv stressed OVX, (v stressed OVX treated with E2 (20 μg daily, sc, and (vi stressed OVX treated with Tualang honey (0.2 g/kg body weight daily, orally. Two months after surgery, the animals were subjected to social instability stress procedure followed by forced swimming test. Struggling time, immobility time, and swimming time were scored. Serum adrenocorticotropic hormone (ACTH and corticosterone levels, and the BDNF concentration were determined using commercially available ELISA kits. Stressed OVX rats displayed increased depressive-like behaviour with significantly increased serum ACTH and corticosterone levels, while the BDNF concentration was significantly decreased compared to other experimental groups. These changes were notably reversed by both E2 and Tualang honey. In conclusion, both Tualang honey and E2 mediate antidepressive-like effects in stressed OVX rats, possibly acting via restoration of hypothalamic-pituitary-adrenal axis and enhancement of the BDNF concentration.

  12. Involvement of the hypothalamic-pituitary-thyroid axis and its interaction with the hypothalamic-pituitary-adrenal axis in the ontogeny of avian thermoregulation: a review

    NARCIS (Netherlands)

    Debonne, M.; Baarendse, P.J.J.; Brand, van den H.; Kemp, B.; Bruggeman, V.; Decuypere, E.

    2008-01-01

    The emergence of thermoregulation in avian species is a complex matter in which neural as well as hormonal processes are involved. In a previous paper, the neural aspects of primary avian thermoregulation were discussed. In this paper the role of the hypothalamus-pituitary-thyroid axis (HPT-axis)

  13. Modeling of the hypothalamic-pituitary-adrenal axis-mediated interaction between the serotonin regulation pathway and the stress response using a Boolean approximation: a novel study of depression

    Science.gov (United States)

    2013-01-01

    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

  14. Polymorphisms of genes related to the hypothalamic-pituitary-adrenal axis influence the cortisol awakening response as well as self-perceived stress.

    Science.gov (United States)

    Li-Tempel, Ting; Larra, Mauro F; Winnikes, Ulrike; Tempel, Tobias; DeRijk, Roel H; Schulz, André; Schächinger, Hartmut; Meyer, Jobst; Schote, Andrea B

    2016-09-01

    The hypothalamus-pituitary-adrenal (HPA) axis is a crucial endocrine system for coping with stress. A reliable and stable marker for the basal state of that system is the cortisol awakening response (CAR). We examined the influence of variants of four relevant candidate genes; the mineralocorticoid receptor gene (MR), the glucocorticoid receptor gene (GR), the serotonin transporter gene (5-HTT) and the gene encoding the brain-derived neurotrophic factor (BDNF) on CAR and self-perceived stress in 217 healthy subjects. We found that polymorphisms of GR influenced both, the basal state of the HPA axis as well as self-perceived stress. MR only associated with self-perceived stress and 5-HTT only with CAR. BDNF did not affected any of the investigated indices. In summary, we suggest that GR variants together with the CAR and supplemented with self reports on perceived stress might be useful indicators for the basal HPA axis activity.

  15. Reducing treatments in cattle superovulation protocols by combining a pituitary extract with a 5% hyaluronan solution: Is it able to diminish activation of the hypothalamic pituitary adrenal axis compared to the traditional protocol?

    Science.gov (United States)

    Biancucci, Andrea; Sbaragli, Tatiana; Comin, Antonella; Sylla, Lakamy; Monaci, Maurizio; Peric, Tanja; Stradaioli, Giuseppe

    2016-03-15

    Traditional superovulation protocols that include multiple gonadotropin treatments are time-consuming and labor intensive. These protocols require multiple handling and restraining of embryo donors. This will likely increase the risks of injuries in both animals and humans and induce stress that may lead to a reduced superovulatory response. These are more evident when working with cattle that are rarely handled or raised on extensive grazing. The objectives of this experiment were to compare the efficacy of a split-injection protocol of porcine pituitary-derived porcine FSH (pFSH) preparation (slow release [SR] group) to the traditional 4-day treatment with pFSH administered twice daily (C group) and to determine the concentrations of cortisol in the hair as a marker of activation of the hypothalamic-pituitary-adrenal (HPA) axis during the two superovulatory treatments. Thirty-two heifers were stimulated twice in a 2 × 2 crossover design and compared for ovarian response and numbers and characteristics of recovered ova-embryo among treatments. No differences between SR and C groups were found in terms of percentage of responsive animals (100% vs. 93.8%) and ovulation rate (83.7 ± 1.1 vs. 79.5 ± 1.0%). A positive correlation was found between the number of follicles responsive to pFSH (2-8 mm) at the beginning of treatments and the superovulatory response, and no differences were found in these follicular populations between the two treatment groups. The numbers of CLs, ova-embryos, fertilized ova, transferable and freezable embryos recovered per cow were found to be significantly higher in SR compared with C group (14.0 ± 1.6 vs. 10.6 ± 1.0, 12.1 ± 1.6 vs. 7.6 ± 1.0, 11.1 ± 1.1 vs. 7.3 ± 1.0, 9.6 ± 1.4 vs. 6.6 ± 1.0, and 9.4 ± 1.4 vs. 6.0 ± 1.0 for SR and C group, respectively). The SR group produced also a significantly greater number of excellent- and/or good-quality embryos compared with the C group. The concentrations of cortisol in the hair at

  16. Multigenerational effects of fetal dexamethasone exposure on the hypothalamic-pituitary-adrenal axis of first- and second-generation female offspring.

    Science.gov (United States)

    Long, Nathan M; Ford, Stephen P; Nathanielsz, Peter W

    2013-03-01

    Synthetic glucocorticoid (sGC) administration to women threatening preterm delivery increases neonatal survival. Evidence shows that fetal exposure to glucocorticoid levels higher than appropriate for current maturation programs offspring development. We examined fetal sGC multigenerational effects on F1 and F2 female offspring hypothalamo-pituitary-adrenal axis (HPAA) function. At 0.7 gestation, pregnant F0 ewes received 4 dexamethasone injections (2 mg, approximately 60 μg/kg(-1) per day(-1), 12 hours apart) or saline (control). F1 female offspring were bred to produce F2 female offspring. Postpubertal HPAA function was tested in F1 and F2 ewes. F1 and F2 ewe lambs showed reduced birthweight and morphometrics. Dexamethasone increased baseline but reduced stimulated HPAA activity in F1 and F2 female offspring. This is the first demonstration that sGC doses in the clinical range have multigenerational effects on hypothalamo-pituitary-adrenal activity in a precocial species, indicating the need for the study of long-term effects of fetal sGC exposure. Copyright © 2013 Mosby, Inc. All rights reserved.

  17. Temperament and hypothalamic-pituitary-adrenal axis function are related and combine to affect growth, efficiency, carcass, and meat quality traits in Brahman steers.

    Science.gov (United States)

    Cafe, L M; Robinson, D L; Ferguson, D M; Geesink, G H; Greenwood, P L

    2011-05-01

    analysis separated these traits into separate components, which in turn had different relations with productivity traits. The largest component of temperament was described similarly by FS and CS, but there were smaller components that these described differently. There were some temperament-related differences in the metabolic status of the steers which were not related to the variation in cortisol, suggesting involvement of the sympatho-adrenal-medullary axis in these temperament-related effects.

  18. The research progress of obstructive sleep apnea-hypopnea syndrome and hypothalamic-pituitary-adrenal axis%阻塞性睡眠呼吸暂停低通气综合征与下丘脑-垂体-肾上腺轴关系研究进展

    Institute of Scientific and Technical Information of China (English)

    李兰凤; 余勤

    2015-01-01

    OSAHS is a serious,prevalent sleep breathing disorder that has signiflcantly high morbidity and mortality when untreated.OSAHS has been shown to be an independent risk factor of serious systemic diseases,such as hypertension,ischemic heart disease,cerebral vascular disease, congestive heart failure and arrhythmias.Many factors could regulate OSAHS in pathogenesis mechanism.Recent researches suggest that the disrupted hypothalamic-pituitary-adrenal (HPA)axis activity plays a great role in OSAHS.In this article,we will review the abnormal HPA axis and its possible mechanisms in patients with OSAHS.%OSAHS 是一种累及多系统并造成多器官损害的睡眠呼吸障碍性疾病,是高血压、心律失常及心、脑血管等多种严重疾病的独立危险因素。OSAHS 是多因素作用的结果,而近年来研究证实下丘脑-垂体-肾上腺(hypothalamic pituitary adrenal,HPA)轴的功能变化与 OSAHS 发病之间存在密切关系。现就 OSAHS 患者 HPA 轴功能变化及可能的相关机制作一综述。

  19. Maus-tratos na infância e psicopatologia no adulto: caminhos para a disfunção do eixo hipotálamo-pituitária-adrenal Childhood maltreatment and adult psychopathology: pathways to hypothalamic-pituitary-adrenal axis dysfunction

    Directory of Open Access Journals (Sweden)

    Marcelo F. Mello

    2009-10-01

    psychopathology, as reflected in hypothalamic-pituitary-adrenal axis dysfunction. METHOD: A selective review of the relevant literature was undertaken in order to identify key and illustrative research findings. RESULTS: There is now a substantial body of preclinical and clinical evidence derived from a variety of experimental paradigms showing how early-life stress is related to hypothalamic-pituitary-adrenal axis function and psychological state in adulthood, and how that relationship can be modulated by other factors. DISCUSSION: The risk for adult psychopathology and hypothalamic-pituitary-adrenal axis dysfunction is related to a complex interaction among multiple experiential factors, as well as to susceptibility genes that interact with those factors. Although acute hypothalamic-pituitary-adrenal axis responses to stress are generally adaptive, excessive responses can lead to deleterious effects. Early-life stress alters hypothalamic-pituitary-adrenal axis function and behavior, but the pattern of hypothalamic-pituitary-adrenal dysfunction and psychological outcome in adulthood reflect both the characteristics of the stressor and other modifying factors. CONCLUSION: Research to date has identified multiple determinants of the hypothalamic-pituitary-adrenal axis dysfunction seen in adults with a history of childhood maltreatment or other early-life stress. Further work is needed to establish whether hypothalamic-pituitary-adrenal axis abnormalities in this context can be used to develop risk endophenotypes for psychiatric and physical illnesses.

  20. The Nutrient and Energy Sensor Sirt1 Regulates the Hypothalamic-Pituitary-Adrenal (HPA) Axis by Altering the Production of the Prohormone Convertase 2 (PC2) Essential in the Maturation of Corticotropin-releasing Hormone (CRH) from Its Prohormone in Male Rats.

    Science.gov (United States)

    Toorie, Anika M; Cyr, Nicole E; Steger, Jennifer S; Beckman, Ross; Farah, George; Nillni, Eduardo A

    2016-03-11

    Understanding the role of hypothalamic neuropeptides and hormones in energy balance is paramount in the search for approaches to mitigate the obese state. Increased hypothalamic-pituitary-adrenal axis activity leads to increased levels of glucocorticoids (GC) that are known to regulate body weight. The axis initiates the production and release of corticotropin-releasing hormone (CRH) from the paraventricular nucleus (PVN) of the hypothalamus. Levels of active CRH peptide are dependent on the processing of its precursor pro-CRH by the action of two members of the family of prohormone convertases 1 and 2 (PC1 and PC2). Here, we propose that the nutrient sensor sirtuin 1 (Sirt1) regulates the production of CRH post-translationally by affecting PC2. Data suggest that Sirt1 may alter the preproPC2 gene directly or via deacetylation of the transcription factor Forkhead box protein O1 (FoxO1). Data also suggest that Sirt1 may alter PC2 via a post-translational mechanism. Our results show that Sirt1 levels in the PVN increase in rats fed a high fat diet for 12 weeks. Furthermore, elevated Sirt1 increased PC2 levels, which in turn increased the production of active CRH and GC. Collectively, this study provides the first evidence supporting the hypothesis that PVN Sirt1 activates the hypothalamic-pituitary-adrenal axis and basal GC levels by enhancing the production of CRH through an increase in the biosynthesis of PC2, which is essential in the maturation of CRH from its prohormone, pro-CRH.

  1. 四逆汤对脓毒症患者下丘脑-垂体-肾上腺轴的影响%Effect of Sini decoction on function of hypothalamic-pituitary-adrenal axis in patients with sepsis

    Institute of Scientific and Technical Information of China (English)

    黄若兰; 张忠; 徐慕娟; 常晓; 乔秋杰; 王玲; 孟新科

    2014-01-01

    Objective To investigate the effects of Sini decoction on function of hypothalamic-pituitary-adrenal axis in patients with sepsis.Methods A prospective single-blind randomized controlled trial was conducted.60 septic patients were divided into three groups with the method of random number table,20 cases in the control group,20 in the Chinese herb group,and 20 in corticoid group.All of them received routine treatment.Patients in Chinese herb group were given Sini decoction in addition (decoction of monkshood 15 g,dried ginger 15 g,honey-fried licorice 10 g) 100 mL/d orally or by nasal feeding,while patients in corticoid group were given hydrocortisone 200 mg/d intravenously instead,both for 7 days.Before the treatment,3 days and 14 days after treatment,blood was collected to determine the levels of adrenocorticotropic hormone (ACTH) and cortisol,and the result of ACTH stimulating test was observed.At the same time,acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score was recorded,and 3-day shock recovery rate and 28-day death rate were also compared among these groups.Results None of the three groups showed different result in ACTH stimulating test (x2=1.101,P=0.605).ACTH in three groups was gradually decreased.Compared with that before treatment,ACTH in Chinese herb group and corticoid groups began to decrease obviously on day 3 (ng/L:29.90 ± 3.31 vs.33.10 ±.3.31,28.20 ±.2.45 vs.33.30 ± 3.84,both P<0.01),while in control group declined ACTH appeared later (on day 14) compared with before treatment (ng/L:29.40 ±5.63 vs.33.50 ±4.89,P<0.05).No obvious difference in ACTH level was showed between the Chinese herb group and the cortical group (both P>0.05).Cortisol level in both Chinese herb and cortical groups showed a raise-fall biphase trend while there was no change in the control.The cortical levels on day 3 in Chinese herb and cortical groups were much higher than that before treatment (μg/L:343.04 ± 31.20 vs.294.70 ±42.10,331.25 ±42

  2. Sympathetic and hypothalamic-pituitary-adrenal asymmetry in generalized anxiety disorder.

    Science.gov (United States)

    Reeves, Jonathan W; Fisher, Aaron J; Newman, Michelle G; Granger, Douglas A

    2016-06-01

    Physiologic investigations of generalized anxiety disorder (GAD) have skewed toward assessment of the autonomic nervous system, largely neglecting hypothalamic-pituitary-adrenal (HPA) axis variables. Although these systems coordinate-suggesting a degree of symmetry-to promote adaptive functioning, most studies opt to monitor either one system or the other. Using a ratio of salivary alpha-amylase (sAA) over salivary cortisol, the present study examined symmetry between the sympathetic nervous system (SNS) and HPA axis in individuals with GAD (n = 71) and healthy controls (n = 37). Compared to healthy controls, individuals with GAD exhibited greater baseline ratios of sAA/cortisol and smaller ratios of sAA/cortisol following a mental arithmetic challenge. We propose that the present study provides evidence for SNS-HPA asymmetry in GAD. Further, these results suggest that increased SNS suppression in GAD may be partially mediated by cortisol activity.

  3. Response of the Hypothalamic-Pituitary-Adrenal System to Repeated Moderate Psychoemotional Stress Exposure Is Associated with Behavioral Parameters.

    Science.gov (United States)

    Goncharova, N D; Chigarova, O A; Oganyan, T E

    2017-05-01

    Individual features of the response of the hypothalamic-pituitary-adrenal axis (HPAA) to repeated moderate stress exposure (daily 2-h restraint stress for 10 days) was studied in young female rhesus monkeys with healthy normal behavior and combined group of female rhesus monkeys with abnormal depression-like and anxious behavior. No between-group differences in the response of ACTH and cortisol were found on day 1. On day 10, a rapid and less pronounced increase in ACTH secretion was observed in all animals in comparison with day 1. Analysis of between-group differences in HPAA response showed higher increase in ACTH level and lower increase in cortisol concentration in animals with depression-like and anxious behavior. These changes were similar to the previously described differences in the response of the adenohypophysis and adrenal cortex to acute restraint stress in old monkeys with similar behavior. Thus, individuals with depression-like and anxious behavior demonstrate impaired stress-induced reactivity of HPAA as early as in young age.

  4. Os efeitos do estresse na função do eixo hipotalâmico-pituitário-adrenal em indivíduos com esquizofrenia The effects of stress on hypothalamic-pituitary-adrenal (HPA axis function in subjects with schizophrenia

    Directory of Open Access Journals (Sweden)

    Francesca L. Guest

    2012-01-01

    Full Text Available Nas últimas décadas, têm surgido evidências sugerindo que a patogênese de desordens psiquiátricas, tais como a esquizofrenia, pode envolver perturbações no eixo hipotalâmico-pituitário-adrenal (HPA. Variações na manifestação desses efeitos poderiam estar relacionadas a diferenças em sintomas clínicos entre os indivíduos afetados, assim como a diferenças na resposta ao tratamento. Tais efeitos podem também ser originados de complexas interações entre genes e fatores ambientais. Aqui, revisamos os efeitos do estresse maternal em anormalidades na regulação do eixo HPA e desenvolvimento de desordens psiquiátricas, incluindo a esquizofrenia. Estudos nessa área podem gerar o aumento do nosso entendimento da natureza multidimensional da esquizofrenia. Posterior pesquisa nesse campo poderia, em última instância, levar ao desenvolvimento de melhores diagnósticos e novas abordagens terapêuticas para essa debilitante condição psiquiátrica.Over the last few decades, evidence has been emerging that the pathogenesis of psychiatric disorders such as schizophrenia can involve perturbations of the hypothalamic-pituitary-adrenal (HPA axis. Variations in the manifestation of these effects could be related to the differences in clinical symptoms between affected individuals as well as to differences in treatment response. Such effects can also arise from the complex interaction between genes and environmental factors. Here, we review the effects of maternal stress on abnormalities in HPA axis regulation and the development of psychiatric disorders including schizophrenia. Studies in this area may prove critical for increasing our understanding of the multi-dimensional nature of schizophrenia. Further research in this area could ultimately lead to the development of improved diagnostics and novel therapeutic approaches for treating this debilitating psychiatric condition.

  5. Os efeitos do estresse na função do eixo hipotalâmico-pituitário-adrenal em indivíduos com esquizofrenia The effects of stress on hypothalamic-pituitary-adrenal (HPA axis function in subjects with schizophrenia

    Directory of Open Access Journals (Sweden)

    Francesca L. Guest

    2013-01-01

    Full Text Available Nas últimas décadas, têm surgido evidências sugerindo que a patogênese de desordens psiquiátricas, tais como a esquizofrenia, pode envolver perturbações no eixo hipotalâmico-pituitário-adrenal (HPA. Variações na manifestação desses efeitos poderiam estar relacionadas a diferenças em sintomas clínicos entre os indivíduos afetados, assim como a diferenças na resposta ao tratamento. Tais efeitos podem também ser originados de complexas interações entre genes e fatores ambientais. Aqui, revisamos os efeitos do estresse maternal em anormalidades na regulação do eixo HPA e desenvolvimento de desordens psiquiátricas, incluindo a esquizofrenia. Estudos nessa área podem gerar o aumento do nosso entendimento da natureza multidimensional da esquizofrenia. Posterior pesquisa nesse campo poderia, em última instância, levar ao desenvolvimento de melhores diagnósticos e novas abordagens terapêuticas para essa debilitante condição psiquiátrica.Over the last few decades, evidence has been emerging that the pathogenesis of psychiatric disorders such as schizophrenia can involve perturbations of the hypothalamic-pituitary-adrenal (HPA axis. Variations in the manifestation of these effects could be related to the differences in clinical symptoms between affected individuals as well as to differences in treatment response. Such effects can also arise from the complex interaction between genes and environmental factors. Here, we review the effects of maternal stress on abnormalities in HPA axis regulation and the development of psychiatric disorders including schizophrenia. Studies in this area may prove critical for increasing our understanding of the multi-dimensional nature of schizophrenia. Further research in this area could ultimately lead to the development of improved diagnostics and novel therapeutic approaches for treating this debilitating psychiatric condition.

  6. Research Progress in Interactions of the Circadian Clock System and the Hypothalamic-pituitary-adrenal Axis%生物钟系统与下丘脑-垂体-肾上腺轴相互作用的研究进展

    Institute of Scientific and Technical Information of China (English)

    韩鹤(综述); 戴泽平(审校)

    2015-01-01

    Organisms have developed concurrent behavioral and physiological adaptations to the strong influence of day/night cycles, as well as to unforeseen, random stress stimuli.These circadian and stress-related responses are achieved by two highly conserved and interrelated regulatory networks,the circadian clock and stress systems, which respectively consist of oscillating molecular pacemakers,the Clock/Bmal1 transcription factors, and the hypothalamic-pituitary-adrenal axis and its end-effector, the glucocorticoid receptor.These systems communicate with each other at different signaling levels,and dysregulation of either system may lead to development of pathologic conditions.%在生物进化的早期,生物体已建立起对昼夜节律变化以及不可预见的随机应激刺激同时产生适应性行为和生理反应的能力,这些昼夜节律及应激相关的反应是通过两个高度保守且密切相关的调控网络-生物钟系统和应激系统来完成的,生物钟系统由震荡分子起搏器,Clock/Bmal1生物钟转录因子构成,应激系统由下丘脑-垂体-肾上腺轴及其末端效应物糖皮质激素受体构成。两者在不同的信号水平上相互联系,任意一个系统出现调节异常均会导致病理情况的发生发展。

  7. Effects of Mongolian Pharmaceutical Betel Shisanwei Ingredients Pill on hypothalamic-pituitary-adrenal axis negative feedback function in rat models of chronic stress-induced depression%慢性应激抑郁模型大鼠下丘脑-垂体-肾上腺轴负反馈功能与蒙药槟榔十三味丸的干预

    Institute of Scientific and Technical Information of China (English)

    包伍叶; 范盎然; 白亮凤; 佟海英; 于雪; 乌吉斯古冷; 李婧; 胡日乐巴根; 张月

    2014-01-01

    BACKGROUND:Mongolian Pharmaceutical Betel Shisanwei Ingredients Pil has achieved good clinical efficacy, but the underlying mechanism remains unclear. OBJECTIVE: To study the effects of Mongolian Pharmaceutical Betel Shisanwei Ingredients Pil on the hypothalamic-pituitary-adrenal axis negative feedback function in the chronic depressed rats, and to explore anti-depression mechanisms of Mongolian Pharmaceutical Betel Shisanwei ingredients pil. METHODS: Eighty male Wistar rats were randomly divided into ten groups according to the sugar consumption test (with eight rats in each group): normal control group, model group, fluoxetine group, high-, medium- and low-dose Betel Shisanwei Ingredients Pil groups, RU486 group, high-, medium- and low-dose Betel Shisanwei Ingredients Pil plus RU486 groups. Except normal control group, the other groups were treated with the chronic unpredictable mild stress stimulation combined with lonely rising, to establish depression models. In the meantime, rats of the high-, medium- and low-dose Betel Shisanwei Ingredients Pil groups were given oral gavage of Betel Shisanwei Ingredients Pil (0.2, 0.4, 0.8 g/kg) for 28 days; rats of the normal control group and model group were intragstricaly administered with sodium carboxymethyl celulose; rats of RU486 group were given abdominal subcutaneous injection of RU486 from day 21 after modeling; rats of the high-, medium- and low-dose Betel Shisanwei Ingredients Pil plus RU486 groups were intragstricaly administered with Betel Shisanwei Ingredients Pil (0.2, 0.4, 0.8 g/kg) and subcutaneous injection of RU486 from day 21. RESULTS AND CONCLUSION:Compared with normal control group, cortisone content increased significantly (P < 0.05), the expression of glucocorticoid receptor mRNA in hippocampus, hypothalamus and pituitary gland decreased significantly, and hypothalamic corticotrophin releasing hormone mRNA expression increased significantly in the model group and RU486 group. Compared with model

  8. Antidepressant-Like Effects of Fractions Prepared from Danzhi-Xiaoyao-San Decoction in Rats with Chronic Unpredictable Mild Stress: Effects on Hypothalamic-Pituitary-Adrenal Axis, Arginine Vasopressin, and Neurotransmitters

    Directory of Open Access Journals (Sweden)

    Li-Li Wu

    2016-01-01

    Full Text Available The aim of the present study was to investigate the antidepressant-like effects of two fractions, including petroleum ether soluble fraction (Fraction A, FA and water-EtOH soluble fraction (Fraction B, FB prepared from the Danzhi-xiaoyao-san (DZXYS by using chronic unpredictable mild stress-induced depressive rat model. The results indicated that DZXYS could ameliorate the depression-like behavior in chronic stress model of rats. The inhibition of hyperactivity of HPA axis and the modulation of monoamine and amino acid neurotransmitters in the hippocampus may be the important mechanisms underlying the action of DZXYS antidepressant-like effect in chronically stressed rats.

  9. Total flavonoids extracted from xiaobuxin-tang on hyperactivity of hypothalamic-pituitary-adrenal axis in mouse learned helplessness model%小补心汤总黄酮对获得性无助小鼠的抗抑郁作用及其对HPA轴功能的影响

    Institute of Scientific and Technical Information of China (English)

    陈力; 张有志; 薛瑞; 于能江; 王玉露; 胡晓旭; 仇志坤; 赵楠; 李云峰; 徐江平

    2015-01-01

    Aim To investigate the effect of the total flaconoids extracted from Xiaobuxin-Tan g ( XBXT-2 ) on the hyperactivity of hypothalamic-pituitary-adrenal axis in mouse learned helplessness model. Methods Learned helplessness was induced by inescapable foot shock stress over 1h session for 5 days. After screen-ing, we divided learned helplessness mice into five groups:IS, inescapable shock;Dlx, dulxetine(20 mg ·kg-1);XBXT-2(25,50 mg·kg-1). Latency to es-cape shocks and escape failure had been recorded. During the test, Dlx(20 mg·kg-1 ) and XBXT-2(25, 50 mg·kg-1 ) were administered intragastrically once daily for four days. Serum corticosterone level and ad-renocorticotropic hormone ( ACTH ) level were meas-ured by ELISA, and expression of glucocorticoids re-ceptor ( GR) α/β and brain-derived neurotrophic fac-tor ( BDNF ) in hippocampus was determined using Western blot method. Results XBXT-2 (25,50 mg· kg-1 ) or duloxetine treatment showed antidepressant effect in mouse learned helplessness model, as demon-strated by the decreased escape failure and escape la-tency. Our ELISA results showed that XBXT-2 or du-loxetine significantly decreased serum corticosterone level and its upstream stress hormone ACTH level in learned helplessness mice. Furthermore, Western blot result demonstrated XBXT-2 treatment increased GRs and BDNF expression in hippocampus. Conclusions XBXT-2 produces significant antidepressant effect on learned helplessness mice. In addition, the modulation of HPA axis produced by XBXT-2 may be important mechanism underlying its antidepressant-like effect in mouse learned helplessness model.%目的:采用小鼠获得性无助模型评价小补心汤总黄酮(XBXT-2)的抗抑郁作用,并探究在应激状态下,XBXT-2对下丘脑-垂体-肾上腺轴( HPA)功能的调节作用。方法采用电脑程序控制的穿梭箱条件反射系统,给予不可逃避的足底电击诱导获得性无助模型,经过穿梭箱回避程序筛选,将成功诱导无

  10. 下丘脑室旁核组胺H3受体对哮喘大鼠下丘脑-垂体-肾上腺轴功能的调控%Effect of histamine H3 receptor in the hypothalamic paraventricular nuclei on hypothalamic-pituitary-adrenal axis in rats with asthma

    Institute of Scientific and Technical Information of China (English)

    季吉; 董榕

    2011-01-01

    Objective: To determine whether histamine H3 receptor in the hypothalamic paraventricular nuclei (PVN) regulates the function of hypothalamic-pituitary-adrenal (HPA) axis in rats with asthma. Method: Rat model for asthma was established by Elwood's methods. A stainless steel jacket was implanted into the PVN using a technique of central three-dimensional position, and R(α)-methylhistamine [R-(α)-MeHA, a H3 receptor agonist] 2 μg or thioperamide (a H3 receptor antagonist) 5 μg was injected into the PVN. Levels of histamine in PVN were detected by high-performance liquid chromatography, and the concentrations of CRH in median eminence, ACTH and CORT in plasma were detected by the radioimmunoassay. Relative levels of IL-10 in both hypothalataus tissue and plasma were measred by double-ligand-linked immunosorbent assay. Result: Levels of histamine in PVN decreased significantly, whereas the concentrations of CRH in median eminence, ACTH and CORT in plasma and the levels of IL-lO in both hypothalamus tissue and plasma were all increased significantly in acute episode asthms rats with treatment of R-(α)-MeHA compared with control rats, and these responses were blocked by treatment of thioperamide, a H3 receptors specific antagonist. Conclusion: Specific activation histamine H3 receptors in PVN can improve the function of HPA in rats with asthma.%目的:探讨哮喘大鼠下丘脑室旁核(paraventricular nuclei,PVN)内组胺H3受体对下丘脑-垂体-肾上腺轴(HPA)功能的调控.方法:根据Elwood方法,制备哮喘模型.采用中枢立体定位技术,在PVN内微量注射组胺H3受体激动剂R-(α)-甲基组胺[R-(α)-methylhistamine,R-(α)-MeHA]2 μg或组胺H3受体拮抗剂Thioperamide 5 μg,注射药物体积均为1μl.高效液相色谱法检测PVN内组胺含量;放射免疫分析方法检测正中隆起中促肾上腺皮质激素释放激素(CRH)和外周血中促肾上腺皮质激素(ACTH)、皮质酮(CORT)含量;酶联免疫吸附法(ELISA

  11. Crossover of the hypothalamic pituitary-adrenal/interrenal (HPA, -thyroid (HPT, and -gonadal (HPG axes in testicular development

    Directory of Open Access Journals (Sweden)

    Diana C. Castañeda Cortés

    2014-08-01

    Full Text Available Besides the well-known function of thyroid hormones (THs for regulating metabolism, it has recently been discovered that THs are also involved in testicular development in mammalian and non-mammalian species. THs, in combination with follicle stimulating hormone (FSH, lead to androgen synthesis in Denio rerio, which results in the onset of spermatogenesis in the testis, potentially relating the hypothalamic-pituitary-thyroid gland (HPT to the hypothalamic-pituitary-gonadal (HPG axes. Furthermore, studies in non-mammalian species have suggested that by stimulating the thyroid-stimulating hormone (TSH, THs can be induced by corticotropin-releasing hormone (CRH. This suggests that the hypothalamic-pituitary-adrenal/interrenal gland (HPA axis might influence the HPT axis. Additionally, it was shown that hormones pertaining to both HPT and HPA could also influence the HPG endocrine axis. For example, high levels of androgens were observed in the testis in Odonthestes bonariensis during a period of stress-induced sex determination, which suggests that stress hormones influence the gonadal fate towards masculinization. Thus, this review highlights the hormonal interactions observed between the HPT, HPA and HPG axes using a comparative approach in order to better understand how these endocrine systems could interact with each other to influence the development of testes.

  12. DMPD: The role of macrophages in the hypothalamic-pituitary-adrenal activation inresponse to endotoxin (LPS). [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 1315450 The role of macrophages in the hypothalamic-pituitary-adrenal activation in...png) (.svg) (.html) (.csml) Show The role of macrophages in the hypothalamic-pituitary-adrenal activation in...response to endotoxin (LPS). PubmedID 1315450 Title The role of macrophages in th

  13. Facilitation of hypothalamic-pituitary-adrenal responses to novel stress following repeated social stress using the resident/intruder paradigm.

    Science.gov (United States)

    Bhatnagar, Seema; Vining, Courtenay

    2003-01-01

    Our goal in these studies was to characterize some specific aspects of hypothalamic-pituitary-adrenal (HPA) activity in rats exposed to repeated social stress. We used a modification of the resident/intruder paradigm in which male intruder rats were subjected to defeat and then separated from the resident by an enclosure for a total of 30 min on Day 1. On Days 2-7, intruder rats were exposed to different resident rats every day through a wire mesh enclosure for 30 min in order to minimize injurious physical contact between the two rats. The intruder rats gained significantly less weight than controls over the 7-day period of stress though basal corticosterone levels and adrenal and thymus weights were not significantly different between the two groups. On Day 8, repeatedly stressed rats exhibited facilitation of HPA responses to novel restraint compared to controls but no differences in negative feedback sensitivity to dexamethasone (0.05 or 0.2 mg/kg) were observed. Thus, the HPA axis of socially stressed rats remains responsive to a stimulus that has never been encountered. Using this type of repeated presentation to an aggressive resident allows us to examine the neuroendocrine and behavioral consequences, and their underlying neural mechanisms, of exposure to a stressor that is social in nature and naturalistic for rodents.

  14. Effect of animal facility construction on basal hypothalamic-pituitary-adrenal and renin-aldosterone activity in the rat.

    Science.gov (United States)

    Raff, Hershel; Bruder, Eric D; Cullinan, William E; Ziegler, Dana R; Cohen, Eric P

    2011-04-01

    Although loud noise and intense vibration are known to alter the behavior and phenotype of laboratory animals, little is known about the effects of nearby construction. We studied the effect of a nearby construction project on the classic stress hormones ACTH, corticosterone, renin, and aldosterone in rats residing in a barrier animal facility before, for the first 3 months of a construction project, and at 1 month after all construction was completed. During some of the construction, noise and vibrations were not obvious to investigators inside the animal rooms. Body weight matched for age was not altered by nearby construction. During nearby construction, plasma ACTH, corticosterone, and aldosterone were approximately doubled compared with those of pre- and postconstruction levels. Expression of CRH mRNA in the paraventricular nucleus of the hypothalamus, CRH receptor and POMC mRNA in the anterior pituitary, and most mRNAs for steroidogenic genes in the adrenal gland were not significantly changed during construction. We conclude that nearby construction can cause a stress response without long-term effects on hypothalamic-pituitary-adrenal axis gene expression and body weight.

  15. Fisiopatología de la disfunción gonadal en la Amenorrea Hipotalámica funcional (AHF y su relación con la activación del eje hipotálamo-hipófiso-adrenal Pathophysiology of gonadal dysfunction in functional Hypothalamic Amenorrhea (FHA and its relation to activation of the hypothalamic-pituitary-adrenal axis

    Directory of Open Access Journals (Sweden)

    León Fiszlejder

    2011-06-01

    adiponectin, among other adipocytokines, and ghrelin, synthesized in the upper gastrointestinal tract. Fat mass reduction in these undernourished women and the resulting decrease in leptin leads to neuropeptide Y (NPY synthesis in the hypothalamus. This peptide, through direct or indirect action mediated by CRH stimulation, and the activation of the opioid and dopaminergic system block the receptors of the GnRH-synthesizing neurons in the arcuate nucleus to inhibit, and thus disturb, the gonadotropin pulsatile activity. The increase in ghrelin also blocks this activity through a complex mechanism: NPY synthesis is stimulated and NPY, in turn, inhibits GABA interneurons, thus altering the suppressant action normally exerted by this neurotransmitter on the CRH. The increase in serotonin levels activates the limbic-hypothalamic-pituitary-adrenal system, probably indirectly, mediated by desensitization of glucocorticoid receptors of CRH immunoreactive neurons, thus inducing secretion. CRH concentrations in cerebrospinal fluid, as well as 24-h mean plasma cortisol concentrations are high, and their half-life is prolonged. Additionally, there is a decrease in CBG associated with elevated free urinary cortisol levels. Basal serum cortisol levels are not suppressed by the administration of dexamethasone and the ACTH response to CRH stimulation is blunted. These findings suggest an alteration of cortisol negative feedback effects on CRH-ACTH secretion. The mechanisms of this resistance to cortisol are not fully elucidated. Animal studies suggest that prolonged stress modifies the density and ratio of gluco- and mineralocorticoid receptors and post-receptor activity. By extrapolation, it could be inferred that this resistance to cortisol in patients with amenorrhea is a mechanism that tends to perpetuate adrenal axis hyperactivity. In addition, the activation of the sympathetic system with the increase in norepinephrine and epinephrine and its association with other factors produces an

  16. Hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes: sex differences in regulation of stress responsivity.

    Science.gov (United States)

    Oyola, Mario G; Handa, Robert J

    2017-08-31

    Gonadal hormones play a key role in the establishment, activation, and regulation of the hypothalamic-pituitary-adrenal (HPA) axis. By influencing the response and sensitivity to releasing factors, neurotransmitters, and hormones, gonadal steroids help orchestrate the gain of the HPA axis to fine-tune the levels of stress hormones in the general circulation. From early life to adulthood, gonadal steroids can differentially affect the HPA axis, resulting in sex differences in the responsivity of this axis. The HPA axis influences many physiological functions making an organism's response to changes in the environment appropriate for its reproductive status. Although the acute HPA response to stressors is a beneficial response, constant activation of this circuitry by chronic or traumatic stressful episodes may lead to a dysregulation of the HPA axis and cause pathology. Compared to males, female mice and rats show a more robust HPA axis response, as a result of circulating estradiol levels which elevate stress hormone levels during non-threatening situations, and during and after stressors. Fluctuating levels of gonadal steroids in females across the estrous cycle are a major factor contributing to sex differences in the robustness of HPA activity in females compared to males. Moreover, gonadal steroids may also contribute to epigenetic and organizational influences on the HPA axis even before puberty. Correspondingly, crosstalk between the hypothalamic-pituitary-gonadal (HPG) and HPA axes could lead to abnormalities of stress responses. In humans, a dysregulated stress response is one of the most common symptoms seen across many neuropsychiatric disorders, and as a result, such interactions may exacerbate peripheral pathologies. In this review, we discuss the HPA and HPG axes and review how gonadal steroids interact with the HPA axis to regulate the stress circuitry during all stages in life.

  17. Effects of Parental Depressive Symptoms on Child Adjustment Moderated by Hypothalamic Pituitary Adrenal Activity: Within- and between-Family Risk

    Science.gov (United States)

    Laurent, Heidemarie K.; Leve, Leslie D.; Neiderhiser, Jenae M.; Natsuaki, Misaki N.; Shaw, Daniel S.; Fisher, Philip A.; Marceau, Kristine; Harold, Gordon T.; Reiss, David

    2013-01-01

    Child hypothalamic pituitary adrenal (HPA) activity was investigated as a moderator of parental depressive symptom effects on child behavior in an adoption sample ("n" = 210 families). Adoptive parents' depressive symptoms and child internalizing and externalizing were assessed at 18, 27, and 54 months, and child morning and evening HPA…

  18. Effect of reproductive status on hypothalamic-pituitary-adrenal (HPA) activity and reactivity in male California mice (Peromyscus californicus).

    Science.gov (United States)

    Harris, Breanna N; Saltzman, Wendy

    2013-03-15

    Previous studies indicate that reproductive condition can alter stress response and glucocorticoid release. Although the functional significance of hypothalamic-pituitary-adrenal (HPA) axis modulation by breeding condition is not fully understood, one possible explanation is the behavior hypothesis, which states that an animal's need to express parental behavior may be driving modulation of the HPA axis. This possibility is consistent with findings of blunted activity and reactivity of the HPA axis in lactating female mammals; however, effects of reproductive status on HPA function have not been well characterized in male mammals that express parental behavior. Therefore, we tested this hypothesis in the monogamous and biparental California mouse. Several aspects of HPA activity were compared in males from three reproductive conditions: virgin males (housed with another male), non-breeding males (housed with a tubally ligated female), and first-time fathers (housed with a female and their first litter of pups). In light of the behavior hypothesis we predicted that new fathers would differ from virgin and non-breeding males in several aspects of HPA function and corticosterone (CORT) output: decreased amplitude of the diurnal rhythm in CORT, a blunted CORT increase following predator-odor stress, increased sensitivity to glucocorticoid negative feedback, and/or a blunted CORT response to pharmacological stimulation. In addition, we predicted that first-time fathers would be more resistant to CORT-induced suppression of testosterone secretion, as testosterone is important for paternal behavior in this species. We found that virgin males, non-breeding males and first-time fathers did not display any CORT differences in diurnal rhythm, response to a predator-odor stressor, or response to pharmacological suppression or stimulation. Additionally, there were no differences in circulating testosterone concentrations. Adrenal mass was, however, significantly lower in new

  19. Increased hypothalamic-pituitary-adrenal drive is associated with decreased appetite and hypoactivation of food motivation neurocircuitry in anorexia nervosa

    Science.gov (United States)

    Lawson, Elizabeth A.; Holsen, Laura M.; DeSanti, Rebecca; Santin, McKale; Meenaghan, Erinne; Herzog, David B.; Goldstein, Jill M.; Klibanski, Anne

    2013-01-01

    Objective Corticotropin releasing hormone (CRH)-mediated hypercortisolemia has been demonstrated in anorexia nervosa (anorexia), a psychiatric disorder characterized by food restriction despite low body weight. While CRH is anorexigenic, downstream cortisol stimulates hunger. Using a food-related fMRI paradigm, we have demonstrated hypoactivation of brain regions involved in food motivation in women with anorexia, even after weight-recovery. The relationship between hypothalamic-pituitary-adrenal (HPA) axis dysregulation and appetite, and the association with food motivation neurocircuitry hypoactivation is unknown in anorexia. We investigated the relationship between HPA activity, appetite and food motivation neurocircuitry hypoactivation in anorexia. Design Cross-sectional study of 36 women [13 anorexia (AN), 10 weight-recovered AN (ANWR), 13 healthy controls (HC)]. Methods Peripheral cortisol and ACTH levels were measured fasting and 30, 60, and 120min after a standardized mixed meal. The Visual Analogue Scale was used to assess homeostatic and hedonic appetite. fMRI was performed during visual processing of food and non-food stimuli to measure brain activation pre- and post-meal. Results In each group, serum cortisol levels decreased following the meal. Mean fasting, 120min post-meal, and nadir cortisol levels were high in AN vs. HC. Mean postprandial ACTH levels were high in ANWR compared to HC and AN. Cortisol levels were associated with lower fasting homeostatic and hedonic appetite, independent of BMI and depressive symptoms. Cortisol levels were also associated with between-group variance in activation in food-motivation brain regions (e.g., hypothalamus, amygdala, hippocampus, OFC and insula). Conclusions HPA activation may contribute to the maintenance of anorexia by suppression of appetitive drive. PMID:23946275

  20. Prenatal glucocorticoid exposure alters hypothalamic-pituitary-adrenal function and blood pressure in mature male guinea pigs.

    Science.gov (United States)

    Banjanin, Sonja; Kapoor, Amita; Matthews, Stephen G

    2004-07-01

    Pregnant guinea pigs were treated with dexamethasone (1 mg kg(-1)) or vehicle on days 40-41, 50-51 and 60-61 of gestation, after which animals delivered normally. Adult male offspring were catheterized at 145 days of age and subjected to tests of hypothalamic-pituitary-adrenal (HPA) axis function in basal and activated states. Animals exposed to dexamethasone in utero (mat-dex) exhibited increased hippocampus-to-brain weight ratio, increased adrenal-to-body weight ratio and increased mean arterial pressure. There were no effects on gestation length, birth weight and postnatal growth. There were no overall differences in diurnal plasma adrenocorticotropic hormone (ACTH) and cortisol profiles, though there were subtle differences during the subjective afternoon between control and mat-dex offspring. A significant decrease in initial ACTH suppression was observed following dexamethasone injection in mat-dex offspring compared to control offspring. Molecular analysis revealed significantly increased MR mRNA expression in the limbic system and particularly in the dentate gyrus in mat-dex offspring. In the anterior pituitary, both pro-opiomelanocortin (POMC) and glucocorticoid receptor (GR) mRNA levels were significantly elevated in mat-dex offspring. In conclusion, (1) repeated prenatal treatment with synthetic glucocorticoid (sGC) permanently programmes organ growth, blood pressure and HPA regulation in mature male offspring and these changes involve modification of corticosteroid receptor expression in the brain and pituitary; (2) the effects of prenatal sGC exposure on HPA function appear to change as a function of age, indicating the importance of investigating HPA and cardiovascular outcome at multiple time points throughout life.

  1. Translational relevance of rodent models of hypothalamic-pituitary-adrenal function and stressors in adolescence

    Directory of Open Access Journals (Sweden)

    Cheryl M. McCormick

    2017-02-01

    Full Text Available Elevations in glucocorticoids that result from environmental stressors can have programming effects on brain structure and function when the exposure occurs during sensitive periods that involve heightened neural development. In recent years, adolescence has gained increasing attention as another sensitive period of development, a period in which pubertal transitions may increase the vulnerability to stressors. There are similarities in physical and behavioural development between humans and rats, and rats have been used effectively as an animal model of adolescence and the unique plasticity of this period of ontogeny. This review focuses on benefits and challenges of rats as a model for translational research on hypothalamic-pituitary-adrenal (HPA function and stressors in adolescence, highlighting important parallels and contrasts between adolescent rats and humans, and we review the main stress procedures that are used in investigating HPA stress responses and their consequences in adolescence in rats. We conclude that a greater focus on timing of puberty as a factor in research in adolescent rats may increase the translational relevance of the findings.

  2. Neuroanatomy and physiology of the avian hypothalamic/pituitary axis: clinical aspects.

    Science.gov (United States)

    Ritchie, Midge

    2014-01-01

    This article describes the anatomy of the avian hypothalamic/pituitary axis, the hypothalamic-pituitary-thyroid axis, the hypothalamic-pituitary-adrenal axis, the hypothalamic-pituitary-gonadal axis, the somatotrophic axis, and neurohypophysis.

  3. O eixo hipotálamo-pituitária-adrenal, a função dos receptores de glicocorticóides e sua importância na depressão The Hypothalamic Pituitary Adrenal axis, Glucocorticoid receptor function and relevance to depression

    Directory of Open Access Journals (Sweden)

    Mario F Juruena

    2004-09-01

    abordagem eficaz para maximizar os efeitos terapêuticos dos antidepressivos. Hipóteses referentes aos mecanismos destes receptores envolvem compostos não esteróides que regulam a função dos RGs via segundos mensageiros. A pesquisa nesta área trará novos entendimentos à fisiopatologia e ao tratamento dos transtornos afetivos, em especial na depressão.OBJECTIVES: Changes in the hypothalamic-pituitary-adrenocortical (HPA system are characteristic of depression. Because the effects of glucocorticoids are mediated by intracellular receptors including, most notably, the glucocorticoid receptor (GR, several studies have examined the number and/or function of GRs in depressed patients. METHODS: Review scientific evidences have consistently demonstrated that GR function is impaired in major depression, resulting in reduced GR-mediated negative feedback on the HPA axis and increased production and secretion of CRF in various brain regions postulated to be involved in the causality of depression. RESULTS: This article summarizes the literature on GR in depression and on the impact of antidepressants on the GR in clinical and preclinical studies, and supports the concept that impaired GR signalling is a key mechanism in the pathogenesis of depression, in the absence of clear evidence of decreased GR expression. The data also indicate that antidepressants have direct effects on the GR, leading to enhanced GR function and increased GR expression. Although the effects of antidepressants on glucocorticoid hormones and their receptors are relevant for the therapeutic action of these drugs, the molecular mechanisms underlying these effects are unclear. We propose that antidepressants in humans could inhibit steroid transporters localised on the blood-brain barrier and in neurones, like the multidrug resistance p-glycoprotein, and thus increase the access of cortisol to the brain and the glucocorticoid-mediated negative feedback on the HPA axis. CONCLUSION: Enhanced cortisol action

  4. How should we interrogate the hypothalamic-pituitary-adrenal axis in patients with suspected hypopituitarism?

    Science.gov (United States)

    Garrahy, Aoife; Agha, Amar

    2016-06-17

    Hypopituitarism is deficiency of one or more pituitary hormones, of which adrenocorticotrophic hormone (ACTH) deficiency is the most serious and potentially life-threatening. It may occur in isolation or, more commonly as part of more widespread pituitary failure. Diagnosis requires demonstration of subnormal cortisol rise in response to stimulation with hypoglycemia, glucagon, ACTH(1-24) or in the setting of acute illness. The choice of diagnostic test should be individualised for the patient and clinical scenario. A random cortisol and ACTH level may be adequate in making a diagnosis in an acutely ill patient with a suspected adrenal crisis e.g. pituitary apoplexy. Often however, dynamic assessment of cortisol reserve is needed. The cortisol response is both stimulus and assay- dependent and normative values should be derived locally. Results must be interpreted within clinical context and with understanding of potential pitfalls of the test used.

  5. Hypothalamic-pituitary-adrenal axis function in survivors of childhood acute lymphoblastic leukemia and healthy controls.

    NARCIS (Netherlands)

    Gordijn, M.S.; Litsenburg, R.R. van; Gemke, R.J.; Bierings, M.B.; Hoogerbrugge, P.M.; Ven, P.M. van de; Heijnen, C.J.; Kaspers, G.J.L.

    2012-01-01

    Of all malignancies in children, acute lymphoblastic leukemia (ALL) is the most common type. Since survival significantly improves over time, treatment-related side effects become increasingly important. Glucocorticoids play an important role in the treatment of ALL, but they may suppress the hypoth

  6. Pre-receptor Regulation of Cortisol in Hypothalamic-Pituitary-Adrenal Axis Functioning an Metabolism

    NARCIS (Netherlands)

    M.J.H.J. Dekker (Marieke)

    2011-01-01

    textabstractGlucocorticoids (GCs) are ubiquitous, nuclear hormones, which are essential for life. In man, the main GC is cortisol, produced by the adrenals, endocrine glands that are situated on top of the kidneys. Cortisol exerts its functions in nearly all tissues and is crucial in the mediation o

  7. Ghrelin's Role in the Hypothalamic-Pituitary-Adrenal Axis Stress Response: Implications for Mood Disorders

    NARCIS (Netherlands)

    Spencer, S.J.; Emmerzaal, T.L.; Kozicz, L.T.; Andrews, Z.B.

    2015-01-01

    Ghrelin is a stomach hormone normally associated with feeding behavior and energy homeostasis. Recent studies highlight that ghrelin targets the brain to regulate a diverse number of functions, including learning, memory, motivation, stress responses, anxiety, and mood. In this review, we discuss re

  8. Escitalopram prolonged fear induced by simulated public speaking and released hypothalamic-pituitary-adrenal axis activation.

    Science.gov (United States)

    Garcia-Leal, C; Del-Ben, C M; Leal, F M; Graeff, F G; Guimarães, F S

    2010-05-01

    Simulated public speaking (SPS) test is sensitive to drugs that interfere with serotonin-mediated neurotransmission and is supposed to recruit neural systems involved in panic disorder. The study was aimed at evaluating the effects of escitalopram, the most selective serotonin-selective reuptake inhibitor available, in SPS. Healthy males received, in a double-blind, randomized design, placebo (n = 12), 10 (n = 17) or 20 (n = 14) mg of escitalopram 2 hours before the test. Behavioural, autonomic and neuroendocrine measures were assessed. Both doses of escitalopram did not produce any effect before or during the speech but prolonged the fear induced by SPS. The test itself did not significantly change cortisol and prolactin levels but under the higher dose of escitalopram, cortisol and prolactin increased immediately after SPS. This fear-enhancing effect of escitalopram agrees with previously reported results with less selective serotonin reuptake inhibitors and the receptor antagonist ritanserin, indicating that serotonin inhibits the fear of speaking in public.

  9. Does the panic attack activate the hypothalamic-pituitary-adrenal axis?

    OpenAIRE

    Graeff Frederico G.; Garcia-Leal Cybele; Del-Ben Cristina M; Guimarães Francisco S.

    2005-01-01

    A bibliographic search has been performed in MEDLINE using cortisol and panic as key-words, occurring in the title and/or in the abstract. Human studies were selected, with no time limit. The following publications were excluded: reviewarticles, case reports, panic attacks in disorders other than panic disorder, and studies on changes that occurred in-between panic attacks. The results showed that real-life panic attacks as well as those induced by selective panicogenic agents such as lactate...

  10. The stress response and the hypothalamic-pituitary-adrenal axis: from molecule to melancholia.

    LENUS (Irish Health Repository)

    O'Connor, T M

    2012-02-03

    Organisms survive by maintaining equilibrium with their environment. The stress system is critical to this homeostasis. Glucocorticoids modulate the stress response at a molecular level by altering gene expression, transcription, and translation, among other pathways. The effect is the inhibition of the functions of inflammatory cells, predominantly mediated through inhibition of cytokines, such as IL-1, IL-6, and TNF-alpha. The central effectors of the stress response are the corticotrophin-releasing hormone (CRH) and locus coeruleus-norepinephrine (LC-NE)\\/sympathetic systems. The CRH system activates the stress response and is subject to modulation by cytokines, hormones, and neurotransmitters. Glucocorticoids also modulate the growth, reproductive and thyroid axes. Abnormalities of stress system activation have been shown in inflammatory diseases such as rheumatoid arthritis, as well as behavioural syndromes such as melancholic depression. These disorders are comparable to those seen in rats whose CRH system is genetically abnormal. Thus, the stress response is central to resistance to inflammatory and behavioural syndromes. In this review, we describe the response to stress at molecular, cellular, neuroendocrine and behavioural levels, and discuss the disease processes that result from a dysregulation of this response, as well as recent developments in their treatment.

  11. Hypothalamic-Pituitary-Adrenal Axis Physiology and Cognitive Control of Behavior in Stress Inoculated Monkeys

    Science.gov (United States)

    Parker, Karen J.; Buckmaster, Christine L.; Lindley, Steven E.; Schatzberg, Alan F.; Lyons, David M.

    2012-01-01

    Monkeys exposed to stress inoculation protocols early in life subsequently exhibit diminished neurobiological responses to moderate psychological stressors and enhanced cognitive control of behavior during juvenile development compared to non-inoculated monkeys. The present experiments extended these findings and revealed that stress inoculated…

  12. Maternal Influences on Epigenetic Programming of the Developing Hypothalamic-Pituitary-Adrenal Axis

    Science.gov (United States)

    Parental and environmental factors during the prenatal and postnatal periods permanently affect the physiology and metabolism of offspring, potentially increasing risk of disease later in life. Underlying mechanisms are beginning to be elucidated, and effects on a number of organ...

  13. Sleep and Endocrinology: Hypothalamic-pituitary- adrenal axis and growth hormone

    Directory of Open Access Journals (Sweden)

    Ravinder Goswami

    2014-03-01

    Full Text Available The supra-chiasmatic nucleus (SCN is the primarily biological clock determining thecircadian rhythm. The neurons of the nucleus making this clock have inherent rhythmand set in biological day and night. These periods usually corresponds to day/night, andindirectly to sleep-wakefulness cycle, in most individuals. Retino-hypothalamic tractcarrying photic information from the retina provides the most important input tomaintain the inherent rhythm of the SCN. The rhythmic discharges from the SCN tovarious neurons of the central nervous system, including pineal gland andhypothalamus, translate into circadian rhythm characteristic of several hormones andmetabolites such as glucose. As a result there is a pattern of hormonal changesoccurring during cycle of sleep wakefulness. Most characteristic of these changes aresurge of melatonin with biological night, surge of growth hormone-releasing hormone(GHRHat onset of sleep and surge of corticotropin-releasinghormone(CRHduring late part of the sleep. The cause and effect relationship of the hypothalamicreleasing hormones and their target hormones on various phases of sleep includinginitial non rapid eye movement (NREM phase at onset of sleep, and rapid eyemovement (REM phase near awakening, is an upcoming research area. Sleepelectroencephalogram (EEG determining the onset of NREM and REM sleep is animportant tool complimenting the studies assessing relationship between varioushormones and phases of sleep. The slow wave activity (SWA corresponds to theintensity of sleep at its onset during the biological night of an individual. Besides,GHRH and CRH, several other peptide and steroid hormones such as growthhormone (GH, its secretagogues, ghrelin, neuropeptide Y, estrogen anddehydroepiandrosterone sulfate are associated or have the potential to change phases ofsleep including initial slow wave-NREM sleep.

  14. Increased hypothalamic-pituitary-adrenal drive is associated with decreased appetite and hypoactivation of food-motivation neurocircuitry in anorexia nervosa.

    Science.gov (United States)

    Lawson, Elizabeth A; Holsen, Laura M; Desanti, Rebecca; Santin, McKale; Meenaghan, Erinne; Herzog, David B; Goldstein, Jill M; Klibanski, Anne

    2013-11-01

    Corticotrophin-releasing hormone (CRH)-mediated hypercortisolemia has been demonstrated in anorexia nervosa (AN), a psychiatric disorder characterized by food restriction despite low body weight. While CRH is anorexigenic, downstream cortisol stimulates hunger. Using a food-related functional magnetic resonance imaging (fMRI) paradigm, we have demonstrated hypoactivation of brain regions involved in food motivation in women with AN, even after weight recovery. The relationship between hypothalamic-pituitary-adrenal (HPA) axis dysregulation and appetite and the association with food-motivation neurocircuitry hypoactivation are unknown in AN. We investigated the relationship between HPA activity, appetite, and food-motivation neurocircuitry hypoactivation in AN. Cross-sectional study of 36 women (13 AN, ten weight-recovered AN (ANWR), and 13 healthy controls (HC)). Peripheral cortisol and ACTH levels were measured in a fasting state and 30, 60, and 120 min after a standardized mixed meal. The visual analog scale was used to assess homeostatic and hedonic appetite. fMRI was performed during visual processing of food and non-food stimuli to measure the brain activation pre- and post-meal. In each group, serum cortisol levels decreased following the meal. Mean fasting, 120 min post-meal, and nadir cortisol levels were high in AN vs HC. Mean postprandial ACTH levels were high in ANWR compared with HC and AN subjects. Cortisol levels were associated with lower fasting homeostatic and hedonic appetite, independent of BMI and depressive symptoms. Cortisol levels were also associated with between-group variance in activation in the food-motivation brain regions (e.g. hypothalamus, amygdala, hippocampus, orbitofrontal cortex, and insula). HPA activation may contribute to the maintenance of AN by the suppression of appetitive drive.

  15. Enhancing offspring hypothalamic-pituitary-adrenal (HPA) regulation via systematic novelty exposure: the influence of maternal HPA function.

    Science.gov (United States)

    Dinces, Sarah M; Romeo, Russell D; McEwen, Bruce S; Tang, Akaysha C

    2014-01-01

    In the rat, repeated brief exposures to novelty early in life can induce long-lasting enhancements in adult cognitive, social, emotional, and neuroendocrine function. Family-to-family variations in these intervention effects on adult offspring are predicted by the mother's ability to mount a rapid corticosterone (CORT) response to the onset of an acute stressor. Here, in Long-Evans rats, we investigated whether neonatal and adulthood novelty exposure, each individually and in combination, can enhance offspring hypothalamic-pituitary-adrenal (HPA) regulation. Using a 2 × 2 within-litter design, one half of each litter were exposed to a relatively novel non-home environment for 3-min (Neo_Novel) daily during infancy (PND 1-21) and the other half of the litter remained in the home cage (Neo_Home); we further exposed half of these two groups to early adulthood (PND 54-63) novelty exposure in an open field and the remaining siblings stayed in their home cages. Two aspects of HPA regulation were assessed: the ability to maintain a low level of resting CORT (CORTB) and the ability to mount a large rapid CORT response (CORTE) to the onset of an acute stressor. Assessment of adult offspring's ability to regulate HPA regulation began at 370 days of age. We further investigated whether the novelty exposure effects on offspring HPA regulation are sensitive to the context of maternal HPA regulation by assessing maternal HPA regulation similarly beginning 7 days after her pups were weaned. We found that at the population level, rats receiving neonatal, but not early adulthood exposure or both, showed a greater rapid CORTE than their home-staying siblings. At the individual family level, these novelty effects are positively associated with maternal CORTE. These results suggest that early experience of novelty can enhance the offspring's ability to mount a rapid response to environmental challenge and the success of such early life intervention is critically dependent upon the

  16. Exploration of the hypothalamic-pituitary-adrenal function as a tool to evaluate animal welfare.

    Science.gov (United States)

    Mormède, Pierre; Andanson, Stéphane; Aupérin, Benoit; Beerda, Bonne; Guémené, Daniel; Malmkvist, Jens; Manteca, Xavier; Manteuffel, Gerhard; Prunet, Patrick; van Reenen, Cornelis G; Richard, Sabine; Veissier, Isabelle

    2007-10-22

    Measuring HPA axis activity is the standard approach to the study of stress and welfare in farm animals. Although the reference technique is the use of blood plasma to measure glucocorticoid hormones (cortisol or corticosterone), several alternative methods such as the measurement of corticosteroids in saliva, urine or faeces have been developed to overcome the stress induced by blood sampling itself. In chronic stress situations, as is frequently the case in studies about farm animal welfare, hormonal secretions are usually unchanged but dynamic testing allows the demonstration of functional changes at several levels of the system, including the sensitization of the adrenal cortex to ACTH and the resistance of the axis to feedback inhibition by corticosteroids (dexamethasone suppression test). Beyond these procedural aspects, the main pitfall in the use of HPA axis activity is in the interpretation of experimental data. The large variability of the system has to be taken into consideration, since corticosteroid hormone secretion is usually pulsatile, follows diurnal and seasonal rhythms, is influenced by feed intake and environmental factors such as temperature and humidity, age and physiological state, just to cite the main sources of variation. The corresponding changes reflect the important role of glucocorticoid hormones in a number of basic physiological processes such as energy metabolism and central nervous system functioning. Furthermore, large differences have been found across species, breeds and individuals, which reflect the contribution of genetic factors and environmental influences, especially during development, in HPA axis functioning. Usually, these results will be integrated with data from behavioral observation, production and pathology records in a comprehensive approach of farm animal welfare.

  17. [Changes in the activity of sympathetic-adrenal medullary system and hypothalamic-pituitary-adrenal system in humans exposed to psychogenic stressors and their effects on immunoreactivity].

    Science.gov (United States)

    Simić, Natasa

    2010-10-01

    This paper gives an account of the functioning of the two systems in different stress induced situations. The activation of the sympathetic-adrenal medullary system is accompanied by the release of catecholamines, while the increased activity of the hypothalamic-pituitary-adrenal system results in the increased release of corticosteroids, especially cortisol. The role of the sympathetic-adrenal medullary system was investigated in immunologic changes induced by laboratory stressors. In the real, as in laboratory conditions, the effects of different stressors on the level of cortisol were studied, as it is the final product of the hypothalamic-pituitary-adrenal system activity. Additional (negative) effects on the functioning of these systems could induce some variables, as an increased consumption of alcohol, smoking, and sleeping disorder. Furthermore, the methodological shortcomings and the selection of subjects in previous studies are discussed. Previous results are also discussed, such as the immunosuppressive effects of cortisol, as well as the mediator and moderator variables in relation to stress and immunoreactivity.

  18. Pigs fed saturated fat/cholesterol have a blunted hypothalamic-pituitary-adrenal function, are insulin resistant and have decreased expression of IRS-1, PGC1α and PPARα.

    Science.gov (United States)

    Lomax, Michael A; Karamanlidis, Georgios; Laws, John; Cremers, Stephanie G; Weinberg, Peter D; Clarke, Lynne

    2013-04-01

    The increasing incidence of insulin resistance has been linked to both increased intake of saturated fatty acids and disruption of the hypothalamic-pituitary-adrenal (HPA) axis. We tested the hypothesis that adding saturated fat/cholesterol to the diet of growing pigs would both disrupt HPA function and cause insulin resistance. Three-month-old pigs were fed either a control (13% energy from fat) or a high saturated fatty acid cholesterol (HSFC) diet (44% energy from fat; 2% cholesterol). After 10 weeks on the diets, intravenous ACTH, insulin and glucose challenges were performed, and after 12 weeks, tissue samples were taken for measurement of mRNA and for lipid-rich aortic lesions. Plasma total, HDL- and LDL-cholesterol were significantly increased in pigs fed the HSFC diet. Cortisol release during the ACTH challenge was suppressed in HSFC-fed pigs which were also more insulin resistant and glucose intolerant than controls. The HSFC diet decreased the expression of insulin receptor (IR) and insulin receptor substrate-1 in muscle and adipose tissue as well as adiponectin and adiponectin receptor 2 expression in fat. The HSFC diet decreased PGC-1α and PPARα expression in muscle but increased PPARα expression in liver. There was a trend for an increase in lipid-stained lesion frequency around the abdominal branches of the aorta in HSFC-fed pigs. We conclude that feeding increased saturated fat to pigs causes disruption in the HPA axis, insulin resistance and decreased muscle and adipose expression of genes controlling insulin signalling and mitochondrial oxidative capacity.

  19. [Correlations between the hypothalamo-pituitary-adrenal axis and the metabolic syndrome].

    Science.gov (United States)

    Góth, Miklós; Hubina, Erika; Korbonits, Márta

    2005-01-09

    The metabolic syndrome has several similarities with Cushing's syndrome (impaired glucose tolerance, hypertension, dyslipidemia, central obesity) suggesting that abnormalities in the regulation of the hypothalamic-pituitary-adrenal axis may have a link with the metabolic syndrome. Several studies suggested an association between the clinical signs of the metabolic syndrome and the increased hypothalamic-pituitary-adrenal axis activity based on increased cortisol concentration at 09.00 a.m. and increased cortisol response to corticotropin. According to the Barker hypothesis the fetal malnutrition could determine adult cardiovascular diseases (coronary heart disease, hypertension), some endocrine and metabolic disorders (obesity, type 2 diabetes and hyperlipidemia). The suggested mechanism of the phenomenon is that the suboptimal fetal nutrition results in glucocorticoid overproduction. The 11beta-hydroxysteroid dehydrogenase (converts biological inactive cortisone to cortisol and vice versa) is an important enzyme in cortisol metabolism. The increased expression of 11beta-hydroxysteroid dehydrogenase type 1 in fat tissue could lead to central obesity and impaired glucose tolerance. The hypothesis that increased corticotropin-releasing hormone production drives the overactive hypothalamo-pituitary-adrenal axis was not proven. Further investigations are needed to identify additional pathogenetic factors and to find new therapeutic possibilities.

  20. HPA-axis stress reactivity in youth depression: evidence of impaired regulatory processes in depressed boys.

    Science.gov (United States)

    Lopez-Duran, Nestor L; McGinnis, Ellen; Kuhlman, Kate; Geiss, Elisa; Vargas, Ivan; Mayer, Stefanie

    2015-01-01

    Given the link between youth depression and stress exposure, efforts to identify related biomarkers have involved examinations of stress regulation systems, including the hypothalamic-pituitary-adrenal (HPA) axis. Despite these vast efforts, the underlying mechanisms at play, as well as factors that may explain heterogeneity of past findings, are not well understood. In this study, we simultaneously examined separate components of the HPA-axis response (e.g. activation intensity, peak levels, recovery) to the Socially Evaluated Cold-Pressor Test in a targeted sample of 115 youth (age 9-16), recruited to overrepresent youth with elevated symptoms of depression. Among youth who displayed a cortisol response to the task, depression symptoms were associated with higher peak responses but not greater rate of activation or recovery in boys only. Among those who did not respond to the task, depression symptoms were associated with greater cortisol levels throughout the visit in boys and girls. Results suggest that depression symptoms are associated with a more prolonged activation of the axis and impaired recovery to psychosocial stressors primarily in boys. We discussed two potential mechanistic explanations of the link between depression symptoms and the duration of activation: (1) inhibitory shift (i.e. point at which the ratio of inhibitory and excitatory input into the axis shifts from greater excitatory to greater inhibitory input) or (2) inhibitory threshold (i.e. level of cortisol exposure required to activate the axis' feedback inhibition system).

  1. Role of the hypothalamic pituitary adrenal axis in the control of the response to stress and infection

    Directory of Open Access Journals (Sweden)

    McCann S.M.

    2000-01-01

    Full Text Available The release of adrenocorticotropin (ACTH from the corticotrophs is controlled principally by vasopressin and corticotropin-releasing hormone (CRH. Oxytocin may augment the release of ACTH under certain conditions, whereas atrial natriuretic peptide acts as a corticotropin release-inhibiting factor to inhibit ACTH release by direct action on the pituitary. Glucocorticoids act on their receptors within the hypothalamus and anterior pituitary gland to suppress the release of vasopressin and CRH and the release of ACTH in response to these neuropeptides. CRH neurons in the paraventricular nucleus also project to the cerebral cortex and subcortical regions and to the locus ceruleus (LC in the brain stem. Cortical influences via the limbic system and possibly the LC augment CRH release during emotional stress, whereas peripheral input by pain and other sensory impulses to the LC causes stimulation of the noradrenergic neurons located there that project their axons to the CRH neurons stimulating them by alpha-adrenergic receptors. A muscarinic cholinergic receptor is interposed between the alpha-receptors and nitric oxidergic interneurons which release nitric oxide that activates CRH release by activation of cyclic guanosine monophosphate, cyclooxygenase, lipoxygenase and epoxygenase. Vasopressin release during stress may be similarly mediated. Vasopressin augments the release of CRH from the hypothalamus and also augments the action of CRH on the pituitary. CRH exerts a positive ultrashort loop feedback to stimulate its own release during stress, possibly by stimulating the LC noradrenergic neurons whose axons project to the paraventricular nucleus to augment the release of CRH.

  2. Disturbances in Hypothalamic-Pituitary-Adrenal Axis and Immunological Activity Differentiating between Unipolar and Bipolar Depressive Episodes

    NARCIS (Netherlands)

    Becking, Karlijn; Spijker, Annet T.; Hoencamp, Erik; Penninx, Brenda W. J. H.; Schoevers, Robert A.; Boschloo, Lynn

    2015-01-01

    Introduction Differentiating bipolar depression (BD) from unipolar depression (UD) is difficult in clinical practice and, consequently, accurate recognition of BD can take as long as nine years. Research has therefore focused on the discriminatory capacities of biomarkers, such as markers of the

  3. Dysfunction of the hypothalamic-pituitary-adrenal axis and functional somatic symptoms : A longitudinal cohort study in the general population

    NARCIS (Netherlands)

    Tak, Lineke M.; Bakker, Stephan J. L.; Rosmalen, Judith G. M.

    In persons with functional somatic symptoms (FSS), no conventionally defined organic pathology is apparent. It has been suggested that complex interactions of psychological, physiological, and social factors are involved in the etiology of FSS. One of the physiological mechanisms that may contribute

  4. Antiglucocorticoid RU 38486 attenuates retention of a behaviour and disinhibits the hypothalamic-pituitary adrenal axis at different brain sites

    NARCIS (Netherlands)

    De Kloet, E R; De Kock, Susanne E.; Schild, V; Veldhuis, H D

    1988-01-01

    Adrenalectomized rats displayed a deficiency in retention of an immobility response acquired during an initial 15-min forced swimming procedure (Porsolt swimming test) and measured 24 h later in a 5-min retest session. The deficit could be restored dose dependently with the glucocorticoid dexamethas

  5. Anticipation of public speaking and sleep and the hypothalamic-pituitary-adrenal axis in women with irritable bowel syndrome.

    Science.gov (United States)

    Heitkemper, M M; Cain, K C; Deechakawan, W; Poppe, A; Jun, S-E; Burr, R L; Jarrett, M E

    2012-07-01

    Evidence suggests that subgroups of patients with irritable bowel syndrome (IBS) are hyper-responsive to a variety of laboratory stress conditions. This study compared sleep quality and night time plasma adrenocorticotropic hormone (ACTH) and serum cortisol levels in response to anticipation of public speaking between 43 women with IBS and 24 healthy control women. In addition, comparisons were made between subgroups within the IBS sample based on predominant stool patterns, 22 IBS-constipation and 21 IBS-diarrhea. Subjects slept three nights in a sleep laboratory, and on the third night serial blood samples were drawn every 20 min from 08:00 PM until awakening. As the subjects had different sleep onsets, each subject's results were synchronized to the first onset of stage 2 sleep. Compared the healthy control group, women with IBS had significantly worse sleep efficiency, and higher cortisol but not ACTH levels over the night. However, there were no IBS bowel pattern subgroup differences. Among IBS subjects, cortisol levels early in the night were higher than found in our previous study with a similar protocol but without the threat of public speaking. These results suggest that a social stressor, such as public speaking prior to bedtime, increases cortisol but not ACTH levels suggesting HPA dysregulation in women with IBS. This response to a social stressor contributes to our understanding of the relationship of stress to symptom expression in IBS. © 2012 Blackwell Publishing Ltd.

  6. Birth by caesarian section alters postnatal function of the hypothalamic-pituitary-adrenal axis in young pigs.

    Science.gov (United States)

    Daniel, J A; Keisler, D H; Sterle, J A; Matteri, R L; Carroll, J A

    1999-03-01

    Eight crossbred sows were selected for the present study (n = 4 vaginal delivery and n = 4 Caesarian section [C-section]). Gestation length did not differ between vaginal delivery and C-section pigs (113.6 +/- .1 and 113.2 +/- .3 d, respectively; P > .16). Blood and tissue samples from 38 pigs were collected at birth. All remaining pigs were sustained with vaginal-delivery sows until 2 wk of age (n = 39). At 2 wk of age, remaining pigs were catheterized for blood sample collection to assess pituitary-adrenal responsiveness to an injection of corticotropin-releasing hormone (CRH; 10 microg/kg). Blood samples were collected at -30, -15, 0, 5, 10, 20, 40, 60, and 90 min; pigs received CRH or saline at time 0. Pigs were killed and tissue samples were collected immediately following the last blood sample. Serum concentrations of ACTH and cortisol (CS) were measured. Total RNA was isolated from the pituitary and adrenal glands to evaluate gene expression for mRNA specific for pro-opiomelanocortin (POMC) and for the ACTH receptor. Centrifuged clot:blood ratio was reduced in the C-section pigs at birth (P pigs. Basal serum concentration of ACTH was greater in C-section than in vaginally delivered pigs at birth (P = .01) but did not differ at 2 wk of age (P = .42). Basal serum concentration of CS was not different at birth (P = .86) but was greater in C-section pigs than in vaginally delivered pigs at 2 wk of age (P .99) between the two groups of pigs following the CRH challenge. However, serum concentration of CS was greater (P pigs following the CRH challenge. Expression of ACTH receptor mRNA tended to be greater in C-section pigs at birth (P .73); however, there was a developmental increase (P pigs.

  7. Alcohol administration attenuates hypothalamic-pituitary-adrenal (HPA) activity in healthy men at low genetic risk for alcoholism, but not in high-risk subjects.

    Science.gov (United States)

    Mick, Inge; Spring, Konstanze; Uhr, Manfred; Zimmermann, Ulrich S

    2013-09-01

    Acute alcohol challenge studies in rodents and naturalistic observations in drinking alcoholics suggest that alcohol stimulates the hypothalamic-pituitary-adrenal (HPA) system. The literature on respective studies in healthy volunteers is more inconsistent, suggesting differential alcohol effects depending on dosage, recent drinking history, family history of alcoholism and alcohol-induced side effects. These papers and the putative pharmacologic mechanisms underlying alcohol effects on the HPA system are reviewed here and compared with a new study, in which we investigated how secretion of adrenocorticotrophin (ACTH) and cortisol is affected by ingestion of 0.6 g/kg ethanol in 33 young healthy socially drinking males with a paternal history of alcoholism (PHP) versus 30 family history negative (FHN) males. Alcohol and placebo were administered in a 2-day, double-blind, placebo controlled crossover design with randomized administration sequence. After administration of placebo, ACTH and cortisol decreased steadily over 130 minutes. In FHN subjects, secretion of both hormones was even more attenuated after alcohol, resulting in significantly lower levels compared with placebo. In PHP subjects, no alcohol effect on hormone secretion could be detected. The ratio of cortisol to ACTH secretion, each expressed as area under the secretion curve, was significantly increased by alcohol in FHN and PHP participants. These results argue against HPA stimulation being a mechanism that promotes the transition from moderate to dependent drinking. The fact that alcohol-induced HPA suppression was not detected in PHP males is consistent with the general concept that subjects at high risk for alcoholism exhibit less-pronounced alcohol effects.

  8. Leptin plasma concentrations, leptin gene expression, and protein localization in the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-adrenal axes of the European beaver (Castor fiber).

    Science.gov (United States)

    Chojnowska, Katarzyna; Czerwinska, Joanna; Kaminski, Tadeusz; Kaminska, Barbara; Kurzynska, Aleksandra; Bogacka, Iwona

    2017-01-01

    The European beaver (Castor fiber) is the largest seasonal free-living rodent in Eurasia. Since the physiology and endocrine system of this species remains unknown, the present study aimed to determine plasma leptin concentrations and the expression of the leptin gene and protein in the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-adrenal (HPG and HPA) axes of beavers during breeding (April), postbreeding (July), and prebreeding (November) seasons. Leptin plasma concentrations did not change in females, whereas in males, leptin plasma concentrations were higher in July than those in April. The presence of leptin mRNA and protein was found in all examined tissues. In females, leptin mRNA expression in the hypothalamus, pituitary, ovaries, and myometrium was markedly higher in July than that in April. In males, leptin mRNA levels varied across the examined tissues of the HPG and HPA. Leptin synthesis increased in the hypothalamus during breeding and postbreeding seasons, but seasonal changes were not observed in the pituitary. In turn, testicular leptin levels were higher during breeding and prebreeding stages. Seasonal differences in the concentrations of leptin mRNA were also observed in the adrenal cortex. In males, leptin mRNA levels were higher in November than those in April or July. In females, leptin synthesis increased in the adrenal cortex during pregnancy relative to other seasons. This is the first ever study to demonstrate seasonal differences in leptin expression in beaver tissues, and our results could suggest that leptin is involved in the regulation of the HPG and HPA axes during various stages of the reproductive cycle in beavers. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Patient specific modeling of the HPA axis related to clinical diagnosis of depression

    DEFF Research Database (Denmark)

    Bangsgaard, Elisabeth; Ottesen, Johnny T.

    2016-01-01

    A novel model of the hypothalamic-pituitary-adrenal axis is presented. The axis is an endocrine system responsible for coping with stress and it is likely to be involved in depression. The dynamics of the system is studied and existence, uniqueness and positivity of the solution and the existence...

  10. Association analyses of depression and genes in the hypothalamus-pituitary-adrenal axis

    DEFF Research Database (Denmark)

    Buttenschøn, Henrietta Nørmølle; Krogh, Jesper; Nielsen, Marit Nyholm;

    2016-01-01

    OBJECTIVE: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been reported in depression. The aim was to investigate the potential association between depression and seven genes regulating or interfering with the HPA axis, including the gene encoding angiotensin converting enzyme...

  11. Effortful Control and Parenting: Associations with HPA Axis Reactivity in Early Childhood

    Science.gov (United States)

    Kryski, Katie R.; Dougherty, Lea R.; Dyson, Margaret W.; Olino, Thomas M.; Laptook, Rebecca S.; Klein, Daniel N.; Hayden, Elizabeth P.

    2013-01-01

    While activation of the hypothalamic-pituitary-adrenal (HPA) axis is an adaptive response to stress, excessive HPA axis reactivity may be an important marker of childhood vulnerability to psychopathology. Parenting, including parent affect during parent-child interactions, may play an important role in shaping the developing HPA system; however,…

  12. In Search of HPA Axis Dysregulation in Child and Adolescent Depression

    Science.gov (United States)

    Guerry, John D.; Hastings, Paul D.

    2011-01-01

    Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in adults with major depressive disorder is among the most consistent and robust biological findings in psychiatry. Given the importance of the adolescent transition to the development and recurrence of depressive phenomena over the lifespan, it is important to have an integrative…

  13. Does HPA-Axis Dysregulation Account for the Effects of Income on Effortful Control and Adjustment in Preschool Children?

    Science.gov (United States)

    Lengua, Liliana J.; Zalewski, Maureen; Fisher, Phil; Moran, Lyndsey

    2013-01-01

    The effects of low income on children's adjustment might be accounted for by disruptions to hypothalamic-pituitary-adrenal (HPA)-axis activity and to the development of effortful control. Using longitudinal data and a community sample of preschool-age children (N?=?306, 36-39?months) and their mothers, recruited to over-represent low-income…

  14. New insights into the role of perinatal HPA-axis dysregulation in postpartum depression.

    Science.gov (United States)

    Glynn, Laura M; Davis, Elysia Poggi; Sandman, Curt A

    2013-12-01

    Postpartum depression affects 10-20% of women following birth and exerts persisting adverse consequences on both mother and child. An incomplete understanding of its etiology constitutes a barrier to early identification and treatment. It is likely that prenatal hormone trajectories represent both markers of risk and also causal factors in the development of postpartum depression. During pregnancy the maternal hypothalamic-pituitary-adrenal axis undergoes dramatic alterations, due in large part, to the introduction of the placenta, a transient endocrine organ of fetal origin. We suggest that prenatal placental and hypothalamic-pituitary-adrenal axis dysregulation is predictive of risk for postpartum depression. In this model the positive feedback loop involving the systems regulating the products of the HPA axis results in higher prenatal levels of cortisol and placental corticotropin-releasing hormone. Greater elevations in placental corticotropin-releasing hormone are related to a disturbance in the sensitivity of the anterior pituitary to cortisol and also perhaps to decreased central corticotropin-releasing hormone secretion. Secondary or tertiary adrenal insufficiencies of a more extreme nature, which emerge during the prenatal period, may be predictive of an extended or more pronounced postpartum hypothalamic-pituitary-adrenal refractory period, which in turn represents a risk factor for development of postpartum depression. In addition to reviewing the relevant existing literature, new data are presented in support of this model which link elevated placental corticotropin-releasing hormone with low levels of ACTH at 3-months postpartum. Future research will further elucidate the role of hypothalamic-pituitary-adrenal axis dysregulation in postpartum depression and also whether prenatal placental and hypothalamic-pituitary-adrenal profiles might prove useful in the early identification of mothers at risk for postpartum mood dysregulation. Copyright © 2013

  15. Hypothalamic-pituitary-adrenal axis and smoking and drinking onset among adolescents: the longitudinal cohort TRacking Adolescents' Individual Lives Survey (TRAILS)

    NARCIS (Netherlands)

    Huizink, A.C.; Greaves-Lord, K.; Oldehinkel, A.J.; Ormel, J.; Verhulst, F.C.

    2009-01-01

    Aims We examined within a prospective longitudinal study whether cortisol levels were associated with smoking or drinking behaviours, taking parental substance use into account. Design The influence of parental substance use on cortisol levels of their adolescent offspring at age 10-12 years was exa

  16. Hypothalamic-pituitary-adrenal axis and smoking and drinking onset among adolescents : the longitudinal cohort TRacking Adolescents' Individual Lives Survey (TRAILS)

    NARCIS (Netherlands)

    Huizink, Anja; Greaves-Lord, K.; Oldehinkel, A.J.; Ormel, J.; Verhulst, F.C.

    2009-01-01

    Aims We examined within a prospective longitudinal study whether cortisol levels were associated with smoking or drinking behaviours, taking parental substance use into account. Design The influence of parental substance use on cortisol levels of their adolescent offspring at age 10-12 years was exa

  17. The role of sleep and the hypothalamic-pituitary-adrenal axis for behavioral and emotional problems in very preterm children during middle childhood.

    Science.gov (United States)

    Perkinson-Gloor, Nadine; Hagmann-von Arx, Priska; Brand, Serge; Holsboer-Trachsler, Edith; Grob, Alexander; Weber, Peter; Lemola, Sakari

    2015-01-01

    Very preterm children are at higher risk to develop behavioral and emotional problems, poor sleep, and altered hypothalamic-pituitary-adrenocortical activity (HPAA). However, knowledge on objective sleep and HPAA as well as their role for the development of behavioral and emotional problems in very preterm children is limited. Fifty-eight very preterm children (HPAA was assessed with four saliva samples in the morning (morning cortisol secretion) and four saliva samples in the evening (evening cortisol secretion). Parents completed the Strengths and Difficulties Questionnaire (SDQ) to assess children's behavioral and emotional problems and a subscale of the Children's Sleep Habits Questionnaire to assess sleep disordered breathing. Very preterm children showed more behavioral and emotional problems (SDQ total behavioral/emotional difficulties, emotional symptoms), poorer sleep (more nocturnal awakenings, more stage 2 sleep, less slow wave sleep), and faster decreasing evening cortisol secretion compared to full-term children. Across the whole sample, more stage 2 sleep and/or less slow wave sleep were associated with more SDQ total behavioral/emotional difficulties, hyperactivity-inattention, and peer problems. Lower morning cortisol secretion and lower evening cortisol secretion were associated with more conduct problems. In very preterm children, increased SDQ total behavioral/emotional difficulties was partially explained by less restorative sleep including more stage 2 sleep and less slow wave sleep. This result points to the importance of restorative sleep for the behavioral and emotional development of very preterm children during middle childhood. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Hypothalamic-pituitary-adrenal-axis dysregulation and double product increases potentiate ischemic heart disease risk in a Black male cohort: the SABPA study.

    Science.gov (United States)

    Malan, Leoné; Schutte, Christiaan E; Alkerwi, Ala'a; Stranges, Saverio; Malan, Nicolaas T

    2017-06-01

    Emotional distress has been associated with a poorer prognosis in myocardial infarction patients. Elevated adrenocorticotrophic hormone (ACTH), lower cortisol, dehydroepiandrosterone sulfate (DHEAS) and cortisol:DHEAS, as measures of emotional distress, might correlate with silent myocardial ischemia (SMI) and workload. Thus, we assessed the relationship between emotional distress, SMI and double product (systolic blood pressure (SBP) × heart rate). Cross-sectional South African biethnic single-set cohorts (N=378), aged 44.7±9.52 years, were investigated. Depressive symptoms (Patient Health Questionnaire-9), anthropometric, fasting blood, 24-h double product and 24-h 2-lead electrocardiogram (ST-segment depression) values were obtained. Blacks, mostly men, had increased depressive symptoms, hyperglycemia, SMI, double product, SBP hypertension and ACTH but lower cortisol, DHEAS and cortisol:DHEAS than their White counterparts. Black men had the highest combined SBP hypertension and below-median cortisol prevalence, 38%, compared with 5.9-13.8% in the other groups. Their SMI was associated with ACTH and cortisol:DHEAS (adj. R(2) 0.29; β 0.27-0.31 (0.12-0.64); P⩽0.05), double product (adj. R(2) 0.29; β 0.38 (0.18-0.57); P=0.050) and SBP hypertension (area under the curve: 0.68 (95% CI: 0.56, 0.80); P=0.042; sensitivity/specificity 49/85%). Double product was positively associated with central obesity in all sex groups and with cortisol in the Black men (PHPAA) showed signs of a hyporesponsive adrenal cortex, suggesting chronic emotional stress in the Black male cohort. In this cohort, HPAA dysregulation and compensatory increases in double product occur as a potential defense mechanism to alleviate perfusion deficits, thereby potentiating ischemic heart disease risk.

  19. Increased Sympathetic and Decreased Parasympathetic Activity Rather Than Changes in Hypothalamic-Pituitary-Adrenal Axis Activity Is Associated with Metabolic Abnormalities

    NARCIS (Netherlands)

    Licht, Carmilla M. M.; Vreeburg, Sophie A.; Dortland, Arianne K. B. van Reedt; Giltay, Erik J.; Hoogendijk, Witte J. G.; DeRijk, Roel H.; Vogelzangs, Nicole; Zitman, Frans G.; de Geus, Eco J. C.; Penninx, Brenda W. J. H.

    Context: Stress is suggested to lead to metabolic dysregulations as clustered in the metabolic syndrome, but the underlying biological mechanisms are not yet well understood. Objective: We examined the relationship between two main str systems, the autonomic nervous system and the

  20. Atrazine Does Not Induce Pica Behavior at Doses that Increase Hypothalamic-Pituitary-Adrenal Axis Activation and Cause Conditioned Taste Avoidance.

    Science.gov (United States)

    Previous work has shown that a single oral administration of atrazine (ATR), a chlorotriazine herbicide, induces dose-dependent increases in plasma adrenocorticotropic hormone (ACTH), serum corticosterone (CORT) and progesterone. The mechanism for these effects is unknown. To tes...

  1. Atrazine Does Not Induce Pica Behavior at Doses that Increase Hypothalamic-Pituitary-Adrenal Axis Activation and Cause Conditioned Taste Avoidance.

    Science.gov (United States)

    Previous work has shown that a single oral administration of atrazine (ATR), a chlorotriazine herbicide, induces dose-dependent increases in plasma adrenocorticotropic hormone (ACTH), serum corticosterone (CORT) and progesterone. The mechanism for these effects is unknown. To tes...

  2. Increased Sympathetic and Decreased Parasympathetic Activity Rather Than Changes in Hypothalamic-Pituitary-Adrenal Axis Activity Is Associated with Metabolic Abnormalities

    NARCIS (Netherlands)

    Licht, Carmilla M. M.; Vreeburg, Sophie A.; Dortland, Arianne K. B. van Reedt; Giltay, Erik J.; Hoogendijk, Witte J. G.; DeRijk, Roel H.; Vogelzangs, Nicole; Zitman, Frans G.; de Geus, Eco J. C.; Penninx, Brenda W. J. H.

    2010-01-01

    Context: Stress is suggested to lead to metabolic dysregulations as clustered in the metabolic syndrome, but the underlying biological mechanisms are not yet well understood. Objective: We examined the relationship between two main str systems, the autonomic nervous system and the hypothalamic-pitui

  3. A Role for Glucocorticoids in Stress-Impaired Reproduction: Beyond the Hypothalamus and Pituitary

    OpenAIRE

    Whirledge, Shannon; Cidlowski, John A.

    2013-01-01

    In addition to the well-characterized role of the sex steroid receptors in regulating fertility and reproduction, reproductive events are also mediated by the hypothalamic-pituitary-adrenal axis in response to an individual's environment. Glucocorticoid secretion in response to stress contributes to the well-characterized suppression of the hypothalamic-pituitary-gonadal axis through central actions in the hypothalamus and pituitary. However, both animal and in vitro studies indicate that oth...

  4. Hair cortisol levels as a retrospective marker of hypothalamic-pituitary axis activity throughout pregnancy: Comparison to salivary cortisol

    OpenAIRE

    D’Anna-Hernandez, Kimberly L.; ROSS, RANDAL G .; Natvig, Crystal L.; Laudenslager, Mark L.

    2011-01-01

    Maternal stress during pregnancy is associated with negative maternal/child outcomes. One potential biomarker of the maternal stress response is cortisol, a product of activity of the hypothalamic-pituitary-adrenal axis. This study evaluated cortisol levels in hair throughout pregnancy as a marker of total cortisol release. Cortisol levels in hair have been shown to be easily quantifiable and may be representative of total cortisol release more than single saliva or serum measures. Hair corti...

  5. Identification of an endocannabinoid system in the rat pars tuberalis-a possible interface in the hypothalamic-pituitary-adrenal system?

    Science.gov (United States)

    Jafarpour, Arsalan; Dehghani, Faramarz; Korf, Horst-Werner

    2017-04-01

    Endocannabinoids (ECs) are ubiquitous endogenous lipid derivatives and play an important role in intercellular communication either in an autocrine/paracrine or in an endocrine fashion. Recently, an intrinsic EC system has been discovered in the hypophysial pars tuberalis (PT) of hamsters and humans. In hamsters, this EC system is under photoperiodic control and appears to influence the secretion of hormones such as prolactin from the adenohypophysis. We investigate the EC system in the PT of the rat, a frequently used species in endocrine research. By means of immunocytochemistry, enzymes involved in EC biosynthesis, e.g., N-arachidonoyl-phosphatidylethanolamine-phospholipase D (NAPE-PLD) and diacylglycerol lipase α (DAGLα) and enzymes involved in EC degradation, e.g., fatty acid amide hydrolase (FAAH) and cyclooxygenase-2 (COX-2), were demonstrated in PT cells of the rat. Immunoreactions (IR) for FAAH and for the cannabinoid receptor CB1 were observed in corticotrope cells of the rat adenohypophysis; these cells were identified by antibodies against proopiomelanocortin (POMC) or adrenocorticotrophic hormone (ACTH). In the outer zone of the median eminence, numerous nerve fibers and terminals displayed CB1 IR. The majority of these were also immunolabeled by an antibody against corticotropin-releasing factor (CRF). These results suggest that the EC system at the hypothalamo-hypophysial interface affects both the CRF-containing nerve fibers and the corticotrope cells in the adenohypophysis. Our data give rise to the hypothesis that, in addition to its well-known role in the reproductive axis, the PT might influence adrenal functions and, thus, the stress response and immune system.

  6. 人参皂苷对慢性应激抑郁模型大鼠行为学及HPA轴、BDNF的影响%Effects of ginsenosides on hypothalamic-pituitary-adrenal function and brain-derived neurotrophic factor in rats exposed to chronic unpredictable mild stress

    Institute of Scientific and Technical Information of China (English)

    刘丽琴; 罗艳; 张瑞睿; 郭建友

    2011-01-01

    Gingseng is commonly used in traditional Chinese medicine community for the treatment of depression-like dis, orders. Ginsenosides is considered to be the major active components of ginseng. Previous studies have demonstrated that ginsenosides produced antidepressant-like action in various mouse models of behavioral despair. The present study aimed to examine whether ginsenosides could affect the chronic unpredictable mild stress (CUMS)-induced depression in rats. The mechanism(s) underlying the antidepressant-like action was investigated by measuring serum corticesterone level, glucocorticoid receptor ( GR), mineralocorticoid receptor (MR) and brain-derived neurotrophic factor (BDNF) mRNA levels in brain tissues. CUMS, being lasted for 6 weeks, caused depression-like behavior in rats, as indicated by the significant decrease in sucrose consumption and increase in immobility time in the forced swim test. Whereas serum corticosterone level was significantly increased in rats exposed to CUMS, expressions of GR mRNA in hippocampus, and BDNF mRNA in hippocampus and frontal cortex, were decreased in CUMS-treated rats. Daily intragastric administration of ginsenosides (12. 5, 25, 50 mg · kg-1) during the six weeks of CUMS significantly suppressed behavioral and biochemical changes induced by CUMS. However, there was no significant difference in MR mRNA level among groups. The results suggest that the antidepressant-like action of ginsenosides is likely mediated by modulating the function of hypothalamic- pituitary -adrenal axis and increasing the expression of BDNF in brain tissues.%目的:探讨人参皂苷对慢性应激所致大鼠抑郁模型的干预作用.方法:通过测定大鼠血清中皮质酮(COR)、糖皮质激素受体(GR)、盐皮质激素受体(MR)和脑组织中神经营养(BDNF)的mRNA表达水平,探讨人参皂苷的抗抑郁机制.结果:与正常组大鼠比较,经过慢性应激6周后大鼠糖水偏好显著下降,强迫游泳测试不动时间

  7. Effects of Aerobic Exercise on Mild Cognitive Impairment

    Science.gov (United States)

    Baker, Laura D.; Frank, Laura L.; Foster-Schubert, Karen; Green, Pattie S.; Wilkinson, Charles W.; McTiernan, Anne; Plymate, Stephen R.; Fishel, Mark A.; Stennis Watson, G.; Cholerton, Brenna A.; Duncan, Glen E.; Mehta, Pankaj D.; Craft, Suzanne

    2011-01-01

    Objectives To examine the effects of aerobic exercise on cognition and other biomarkers associated with Alzheimer disease pathology for older adults with mild cognitive impairment, and assess the role of sex as a predictor of response. Design Six-month, randomized, controlled, clinical trial. Setting Veterans Affairs Puget Sound Health Care System clinical research unit. Participants Thirty-three adults (17 women) with amnestic mild cognitive impairment ranging in age from 55 to 85 years (mean age,70 years). Intervention Participants were randomized either to a high-intensity aerobic exercise or stretching control group. The aerobic group exercised under the supervision of a fitness trainer at 75% to 85% of heart rate reserve for 45 to 60 min/d, 4 d/wk for 6 months. The control group carried out supervised stretching activities according to the same schedule but maintained their heart rate at or below 50% of their heart rate reserve. Before and after the study, glucometabolic and treadmill tests were performed and fat distribution was assessed using dual-energy x-ray absorptiometry. At baseline, month 3, and month 6, blood was collected for assay and cognitive tests were administered. Main Outcome Measures Performance measures on Symbol-Digit Modalities, Verbal Fluency, Stroop, Trails B, Task Switching, Story Recall, and List Learning. Fasting plasma levels of insulin, cortisol, brain-derived neurotrophic factor, insulinlike growth factor-I, and β-amyloids 40 and 42. Results Six months of high-intensity aerobic exercise had sex-specific effects on cognition, glucose metabolism, and hypothalamic-pituitary-adrenal axis and trophic activity despite comparable gains in cardiorespiratory fitness and body fat reduction. For women, aerobic exercise improved performance on multiple tests of executive function, increased glucose disposal during the metabolic clamp, and reduced fasting plasma levels of insulin, cortisol, and brain-derived neurotrophic factor. For men

  8. Increased plasma levels of circulating cell-free mitochondrial DNA in suicide attempters: associations with HPA-axis hyperactivity.

    Science.gov (United States)

    Lindqvist, D; Fernström, J; Grudet, C; Ljunggren, L; Träskman-Bendz, L; Ohlsson, L; Westrin, Å

    2016-12-06

    Preclinical data suggest that chronic stress may cause cellular damage and mitochondrial dysfunction, potentially leading to the release of mitochondrial DNA (mtDNA) into the bloodstream. Major depressive disorder has been associated with an increased amount of mtDNA in leukocytes from saliva samples and blood; however, no previous studies have measured plasma levels of free-circulating mtDNA in a clinical psychiatric sample. In this study, free circulating mtDNA was quantified in plasma samples from 37 suicide attempters, who had undergone a dexamethasone suppression test (DST), and 37 healthy controls. We hypothesized that free circulating mtDNA would be elevated in the suicide attempters and would be associated with hypothalamic-pituitary-adrenal (HPA)-axis hyperactivity. Suicide attempters had significantly higher plasma levels of free-circulating mtDNA compared with healthy controls at different time points (pre- and post-DST; all P-valuesSuicide attempters may have elevated plasma levels of free-circulating mtDNA, which are related to impaired HPA-axis negative feedback. This peripheral index is consistent with an increased cellular or mitochondrial damage. The specific cells and tissues contributing to plasma levels of free-circulating mtDNA are not known, as is the specificity of this finding for suicide attempters. Future studies are needed in order to better understand the relevance of increased free-circulating mtDNA in relation to the pathophysiology underlying suicidal behavior and depression.

  9. The caffeine-binding adenosine A2A receptor induces age-like HPA-axis dysfunction by targeting glucocorticoid receptor function.

    Science.gov (United States)

    Batalha, Vânia L; Ferreira, Diana G; Coelho, Joana E; Valadas, Jorge S; Gomes, Rui; Temido-Ferreira, Mariana; Shmidt, Tatiana; Baqi, Younis; Buée, Luc; Müller, Christa E; Hamdane, Malika; Outeiro, Tiago F; Bader, Michael; Meijsing, Sebastiaan H; Sadri-Vakili, Ghazaleh; Blum, David; Lopes, Luísa V

    2016-08-11

    Caffeine is associated with procognitive effects in humans by counteracting overactivation of the adenosine A2A receptor (A2AR), which is upregulated in the human forebrain of aged and Alzheimer's disease (AD) patients. We have previously shown that an anti-A2AR therapy reverts age-like memory deficits, by reestablishment of the hypothalamic-pituitary-adrenal (HPA) axis feedback and corticosterone circadian levels. These observations suggest that A2AR over-activation and glucocorticoid dysfunction are key events in age-related hippocampal deficits; but their direct connection has never been explored. We now show that inducing A2AR overexpression in an aging-like profile is sufficient to trigger HPA-axis dysfunction, namely loss of plasmatic corticosterone circadian oscillation, and promotes reduction of GR hippocampal levels. The synaptic plasticity and memory deficits triggered by GR in the hippocampus are amplified by A2AR over-activation and were rescued by anti-A2AR therapy; finally, we demonstrate that A2AR act on GR nuclear translocation and GR-dependent transcriptional regulation. We provide the first demonstration that A2AR is a major regulator of GR function and that this functional interconnection may be a trigger to age-related memory deficits. This supports the idea that the procognitive effects of A2AR antagonists, namely caffeine, on Alzheimer's and age-related cognitive impairments may rely on its ability to modulate GR actions.

  10. The caffeine-binding adenosine A2A receptor induces age-like HPA-axis dysfunction by targeting glucocorticoid receptor function

    Science.gov (United States)

    Batalha, Vânia L.; Ferreira, Diana G.; Coelho, Joana E.; Valadas, Jorge S.; Gomes, Rui; Temido-Ferreira, Mariana; Shmidt, Tatiana; Baqi, Younis; Buée, Luc; Müller, Christa E.; Hamdane, Malika; Outeiro, Tiago F.; Bader, Michael; Meijsing, Sebastiaan H.; Sadri-Vakili, Ghazaleh; Blum, David; Lopes, Luísa V.

    2016-01-01

    Caffeine is associated with procognitive effects in humans by counteracting overactivation of the adenosine A2A receptor (A2AR), which is upregulated in the human forebrain of aged and Alzheimer’s disease (AD) patients. We have previously shown that an anti-A2AR therapy reverts age-like memory deficits, by reestablishment of the hypothalamic-pituitary-adrenal (HPA) axis feedback and corticosterone circadian levels. These observations suggest that A2AR over-activation and glucocorticoid dysfunction are key events in age-related hippocampal deficits; but their direct connection has never been explored. We now show that inducing A2AR overexpression in an aging-like profile is sufficient to trigger HPA-axis dysfunction, namely loss of plasmatic corticosterone circadian oscillation, and promotes reduction of GR hippocampal levels. The synaptic plasticity and memory deficits triggered by GR in the hippocampus are amplified by A2AR over-activation and were rescued by anti-A2AR therapy; finally, we demonstrate that A2AR act on GR nuclear translocation and GR-dependent transcriptional regulation. We provide the first demonstration that A2AR is a major regulator of GR function and that this functional interconnection may be a trigger to age-related memory deficits. This supports the idea that the procognitive effects of A2AR antagonists, namely caffeine, on Alzheimer’s and age-related cognitive impairments may rely on its ability to modulate GR actions. PMID:27510168

  11. Brain changes underlying the long-term effects of a single previous exposure to emotional or systemic stressors in rats a view from the hypothalamic-pituitary-adrenal axis /

    OpenAIRE

    Vallès i Sánchez, Astrid

    2003-01-01

    Descripció del recurs: el 31 d'octubre de 2003 Estímuls estressants bàsicament emocionals, com la immobilització en taula (IMO), exerceixen efectes a llarg termini sobre l'activitat de l'eix hipotalàmic-pituïtari-adrenal (HPA) en rates adultes. Aquests efectes es caracteritzen per una desensibilització, primer a nivell perifèric (d'adrenocorticotropina (ACTH) y de corticosterona al cap d'uns dies) i més tard a nivell central (d'mRNA de corticoliberina (CRF) en el nucli paraventricular de l...

  12. THE ASSESSMENT OF THE FUNCTIONAL-CAPACITY OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS BY MEASUREMENT OF BASAL PLASMA AND URINARY CORTISOL IN COMPARISON WITH INSULIN-INDUCED HYPOGLYCEMIA AND METYRAPONE TESTS

    NARCIS (Netherlands)

    DELANGE, WE; SLUITER, WJ

    1993-01-01

    In 58 patients with a pituitary adenoma or hypothalamic-pituitary disease an insulin-induced hypoglycaemia test and a metyrapone test were performed. The results of these tests were compared with morning plasma cortisol levels and daily urinary cortisol excretion as indicators of insufficiency of th

  13. The importance of the way we are: The role of personality in the functioning of the Autonomic Nervous System and the Hypothalamic-Pituitary-Adrenal axis in older people

    OpenAIRE

    Puig Pérez, Sara

    2016-01-01

    Sólo unos pocos estudios han investigado el papel protector o perjudicial de factores psicológicos sobre los principales sistemas fisiológicos involucrados en la respuesta de estrés en personas mayores. Considerando la importancia que éstos sistemas fisiológicos en la salud, el objetivo principal de esta tesis doctoral es investigar los posibles factores psicológicos que protegen o contribuyen a un mal funcionamiento del SNA y del eje HHA. Estudio 1 En el presente estudio nos hemos...

  14. Lithium ameliorates sleep deprivation-induced mania-like behavior, hypothalamic-pituitary-adrenal (HPA) axis alterations, oxidative stress and elevations of cytokine concentrations in the brain and serum of mice.

    Science.gov (United States)

    Valvassori, Samira S; Resende, Wilson R; Dal-Pont, Gustavo; Sangaletti-Pereira, Heron; Gava, Fernanda F; Peterle, Bruna R; Carvalho, André F; Varela, Roger B; Dal-Pizzol, Felipe; Quevedo, João

    2017-06-01

    The goal of the present study was to investigate the effects of lithium administration on behavior, oxidative stress parameters and cytokine levels in the periphery and brain of mice subjected to an animal model of mania induced by paradoxical sleep deprivation (PSD). Male C57 mice were treated with saline or lithium for 7 days. The sleep deprivation protocol started on the 5th day during for the last 36 hours of the treatment period. Immediately after the sleep deprivation protocol, animals locomotor activity was evaluated and serum and brain samples was extracted to evaluation of corticosterone and adrenocorticotropic hormone circulating levels, oxidative stress parameters and citokynes levels. The results showed that PSD induced hyperactivity in mice, which is considered a mania-like behavior. PSD increased lipid peroxidation and oxidative damage to DNA, as well as causing alterations to antioxidant enzymes in the frontal cortex, hippocampus and serum of mice. In addition, PSD increased the levels of cytokines in the brains of mice. Treatment with lithium prevented the mania-like behavior, oxidative damage and cytokine alterations induced by PSD. Improving our understanding of oxidative damage in biomolecules, antioxidant mechanisms and the inflammatory system - alterations presented in the animal models of mania - is important in helping us to improve our knowledge concerning the pathophysiology of BD, and the mechanisms of action employed by mood stabilizers. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Central nervous system lipocalin-type prostaglandin D2-synthase is correlated with orexigenic neuropeptides, visceral adiposity and markers of the hypothalamic-pituitary-adrenal axis in obese humans.

    Science.gov (United States)

    Elias, E; Benrick, A; Behre, C J; Ekman, R; Zetterberg, H; Stenlöf, K; Wallenius, V

    2011-06-01

    Lipocalin-type prostaglandin D2-synthase (L-PGDS) is the main producer of prostaglandin D2 (PGD2) in the central nervous system (CNS). Animal data suggest effects of central nervous L-PGDS in the regulation of food intake and obesity. No human data are available. We hypothesised that a role for CNS L-PGDS in metabolic function in humans would be reflected by correlations with known orexigenic neuropeptides. Cerebrospinal fluid (CSF) and serum samples were retrieved from 26 subjects in a weight loss study, comprising a 3-week dietary lead-in followed by 12-weeks of leptin or placebo treatment. At baseline, CSF L-PGDS was positively correlated with neuropeptide Y (NPY) (ρ = 0.695, P obesity by interaction with the neuroendocrine circuits regulating appetite and fat distribution. Further interventional studies will be needed to characterise these interactions in more detail.

  16. Depletion of FKBP51 in female mice shapes HPA axis activity.

    Directory of Open Access Journals (Sweden)

    Lianne Hoeijmakers

    Full Text Available Psychiatric disorders such as depressive disorders and posttraumatic stress disorder are a major disease burden worldwide and have a higher incidence in women than in men. However, the underlying mechanism responsible for the sex-dependent differences is not fully understood. Besides environmental factors such as traumatic life events or chronic stress, genetic variants contribute to the development of such diseases. For instance, variations in the gene encoding the FK506 binding protein 51 (FKBP51 have been repeatedly associated with mood and anxiety. FKBP51 is a negative regulator of the glucocorticoid receptor and thereby of the hypothalamic-pituitary-adrenal axis that also interacts with other steroid hormone receptors such as the progesterone and androgen receptors. Thus, the predisposition of women to psychiatric disorders and the interaction of female hormones with FKBP51 and the glucocorticoid receptor implicate a possible difference in the regulation of the hypothalamic-pituitary-adrenal axis in female FKBP51 knockout (51KO mice. Therefore, we investigated neuroendocrine, behavioural and physiological alterations relevant to mood disorders in female 51KO mice. Female 51KOs and wild type littermates were subjected to various behavioural tests, including the open field, elevated plus maze and forced swim test. The neuroendocrine profile was investigated under basal conditions and in response to an acute stressor. Furthermore, we analysed the mRNA expression levels of the glucocorticoid receptor and corticotrophin release hormone in different brain regions. Overall, female 51KO mice did not display any overt behavioural phenotype under basal conditions, but showed a reduced basal hypothalamic-pituitary-adrenal axis activity, a blunted response to, and an enhanced recovery from, acute stress. These characteristics strongly overlap with previous studies in male 51KO mice indicating that FKBP51 shapes the behavioural and neuroendocrine

  17. Depletion of FKBP51 in female mice shapes HPA axis activity.

    Science.gov (United States)

    Hoeijmakers, Lianne; Harbich, Daniela; Schmid, Bianca; Lucassen, Paul J; Wagner, Klaus V; Schmidt, Mathias V; Hartmann, Jakob

    2014-01-01

    Psychiatric disorders such as depressive disorders and posttraumatic stress disorder are a major disease burden worldwide and have a higher incidence in women than in men. However, the underlying mechanism responsible for the sex-dependent differences is not fully understood. Besides environmental factors such as traumatic life events or chronic stress, genetic variants contribute to the development of such diseases. For instance, variations in the gene encoding the FK506 binding protein 51 (FKBP51) have been repeatedly associated with mood and anxiety. FKBP51 is a negative regulator of the glucocorticoid receptor and thereby of the hypothalamic-pituitary-adrenal axis that also interacts with other steroid hormone receptors such as the progesterone and androgen receptors. Thus, the predisposition of women to psychiatric disorders and the interaction of female hormones with FKBP51 and the glucocorticoid receptor implicate a possible difference in the regulation of the hypothalamic-pituitary-adrenal axis in female FKBP51 knockout (51KO) mice. Therefore, we investigated neuroendocrine, behavioural and physiological alterations relevant to mood disorders in female 51KO mice. Female 51KOs and wild type littermates were subjected to various behavioural tests, including the open field, elevated plus maze and forced swim test. The neuroendocrine profile was investigated under basal conditions and in response to an acute stressor. Furthermore, we analysed the mRNA expression levels of the glucocorticoid receptor and corticotrophin release hormone in different brain regions. Overall, female 51KO mice did not display any overt behavioural phenotype under basal conditions, but showed a reduced basal hypothalamic-pituitary-adrenal axis activity, a blunted response to, and an enhanced recovery from, acute stress. These characteristics strongly overlap with previous studies in male 51KO mice indicating that FKBP51 shapes the behavioural and neuroendocrine phenotype independent of

  18. Melatonin Improves Outcomes of Heatstroke in Mice by Reducing Brain Inflammation and Oxidative Damage and Multiple Organ Dysfunction

    Directory of Open Access Journals (Sweden)

    Yu-Feng Tian

    2013-01-01

    Full Text Available We report here that when untreated mice underwent heat stress, they displayed thermoregulatory deficit (e.g., animals display hypothermia during room temperature exposure, brain (or hypothalamic inflammation, ischemia, oxidative damage, hypothalamic-pituitary-adrenal axis impairment (e.g., decreased plasma levels of both adrenocorticotrophic hormone and corticosterone during heat stress, multiple organ dysfunction or failure, and lethality. Melatonin therapy significantly reduced the thermoregulatory deficit, brain inflammation, ischemia, oxidative damage, hypothalamic-pituitary-adrenal axis impairment, multiple organ dysfunction, and lethality caused by heat stroke. Our data indicate that melatonin may improve outcomes of heat stroke by reducing brain inflammation, oxidative damage, and multiple organ dysfunction.

  19. Adaptation of the pituitary-adrenal axis to daily repeated forced swim exposure in rats is dependent on the temperature of water.

    Science.gov (United States)

    Rabasa, Cristina; Delgado-Morales, Raúl; Gómez-Román, Almudena; Nadal, Roser; Armario, Antonio

    2013-11-01

    Comparison of exposure to certain predominantly emotional stressors reveals a qualitatively similar neuroendocrine response profile as well as a reduction of physiological responses after daily repeated exposure (adaptation). However, particular physical components of the stressor may interfere with adaptation. As defective adaptation to stress can enhance the probability to develop pathologies, we studied in adult male rats (n = 10/group) swimming behavior (struggling, immobility and mild swim) and physiological responses (ACTH, corticosterone and rectal temperature) to daily repeated exposure to forced swim (20 min, 13 d) at 25 or 36 °C (swim25 or swim36). Rats were repeatedly blood-sampled by tail-nick and hormones measured by radioimmunoassay. Some differences were observed between the two swim temperature groups after the first exposure to forced swim: (a) active behaviors were greater in swim25 than swim36 groups; (b) swim25 but not swim36 caused hypothermia; and (c) swim36 elicited the same ACTH response as swim25, but plasma corticosterone concentration was lower for swim36 at 30 min post-swim. After daily repeated exposure, adaptation in ACTH secretion was observed with swim36 already on day 4, whereas with swim25 adaptation was not observed until day 13 and was of lower magnitude. Nevertheless, after repeated exposure to swim25 a partial protection from hypothermia was observed and the two swim conditions resulted in progressive reduction of active behaviors. Thus, daily repeated swim at 25 °C impairs adaptation of the hypothalamic-pituitary-adrenal axis as compared to swim at 36 °C, supporting the hypothesis that certain physical components of predominantly emotional stressors can interfere with the process of adaptation.

  20. Maternal separation as a model of brain-gut axis dysfunction.

    LENUS (Irish Health Repository)

    O'Mahony, Siobhain M

    2011-03-01

    Early life stress has been implicated in many psychiatric disorders ranging from depression to anxiety. Maternal separation in rodents is a well-studied model of early life stress. However, stress during this critical period also induces alterations in many systems throughout the body. Thus, a variety of other disorders that are associated with adverse early life events are often comorbid with psychiatric illnesses, suggesting a common underlying aetiology. Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that is thought to involve a dysfunctional interaction between the brain and the gut. Essential aspects of the brain-gut axis include spinal pathways, the hypothalamic pituitary adrenal axis, the immune system, as well as the enteric microbiota. Accumulating evidence suggest that stress, especially in early life, is a predisposing factor to IBS.

  1. Daily family stress and HPA axis functioning during adolescence: The moderating role of sleep.

    Science.gov (United States)

    Chiang, Jessica J; Tsai, Kim M; Park, Heejung; Bower, Julienne E; Almeida, David M; Dahl, Ronald E; Irwin, Michael R; Seeman, Teresa E; Fuligni, Andrew J

    2016-09-01

    The present study examined the moderating role of sleep in the association between family demands and conflict and hypothalamic-pituitary-adrenal (HPA) axis functioning in a sample of ethnically diverse adolescents (n=316). Adolescents completed daily diary reports of family demands and conflict for 15 days, and wore actigraph watches during the first 8 nights to assess sleep. Participants also provided five saliva samples for 3 consecutive days to assess diurnal cortisol rhythms. Regression analyses indicated that sleep latency and efficiency moderated the link between family demands and the cortisol awakening response. Specifically, family demands were related to a smaller cortisol awakening response only among adolescents with longer sleep latency and lower sleep efficiency. These results suggest that certain aspects of HPA axis functioning may be sensitive to family demands primarily in the context of longer sleep latency and lower sleep efficiency.

  2. Response of the nitrergic system to activation of the neuroendocrine stress axis

    Directory of Open Access Journals (Sweden)

    Hsiao-Jou Cortina eChen

    2015-01-01

    Full Text Available Exposure to stressful stimuli causes activation of the hypothalamic-pituitary-adrenal axis which rapidly releases high concentrations of glucocorticoid stress hormones, resulting in increased cellular metabolism and spontaneous oxygen and nitrogen radical formation. High concentrations of nitrogen radicals, including nitric oxide, cause damage to cellular proteins in addition to inhibiting components of the mitochondrial transport chain, leading to cellular energy deficiency. During stress exposure, pharmacological inhibition of nitric oxide production reduces indicators of anxiety- and depressive-like behavior in animal models. Therefore, the purpose of this review is to present an overview of the current literature on stress-evoked changes in the nitrergic system, particularly within neural tissue.

  3. Suicidal intent and the HPA-axis characteristics of suicide attempters with major depressive disorder and adjustment disorders.

    Science.gov (United States)

    Lindqvist, Daniel; Träskman-Bendz, Lil; Vang, Fredrik

    2008-01-01

    The main purpose of the study was to investigate Hypothalamic-Pituitary-Adrenal (HPA) axis characteristics in relation to suicidal intent among suicide attempters with Major Depressive Disorder (MDD) and Adjustment Disorders (AD). The relationship between suicidal intent, assessed by means of the Suicidal Intent Scale (SIS), and serum cortisol after a Dexamethasone Suppression Test (DST) was investigated in 78 suicide attempters, divided into diagnostic subgroups. There was a significant negative correlation between suicidal intent and post DST cortisol in patients with MDD. Our findings may be attributed to pathophysiological processes, where a high suicidal intent is revealed during a potential chronic course of MDD, which in turn results in a seemingly normal stress system.

  4. Disruption of the neuregulin 1 gene in the rat alters HPA axis activity and behavioral responses to environmental stimuli.

    Science.gov (United States)

    Taylor, S B; Taylor, A R; Markham, J A; Geurts, A M; Kanaskie, B Z; Koenig, J I

    2011-08-03

    Exposure to stress can result in an increased risk for psychiatric disorders, especially among genetically predisposed individuals. Neuregulin 1 (NRG1) is a susceptibility gene for schizophrenia and is also associated with psychotic bipolar disorder. In the rat, the neurons of the hypothalamic paraventricular nucleus show strong expression of Nrg1 mRNA. In patients with schizophrenia, a single nucleotide polymorphism in the 5' region of NRG1 interacts with psychosocial stress to affect reactivity to expressed emotion. However, there is virtually no information on the role of NRG1 in hypothalamic-pituitary-adrenal axis function, and whether the protein is expressed in the paraventricular nucleus is unknown. The present studies utilize a unique line of Nrg1 hypomorphic rats (Nrg1(Tn)) generated by gene trapping with the Sleeping Beauty transposon. We first established that the Nrg1(Tn) rats displayed reduced expression of both the mRNA and protein corresponding to the Type II NRG1 isoform. After confirming, using wild type animals, that Type II NRG1 is expressed in the neurocircuitry involved in regulating hypothalamic-pituitary-adrenal axis responses to environmental stimuli, the Nrg1(Tn) rats were then used to test the hypothesis that altered expression of Type II NRG1 disrupts stress regulation and reactivity. In support of this hypothesis, Nrg1(Tn) rats have disrupted basal and acute stress recovery corticosterone secretion, differential changes in expression of glucocorticoid receptors in the pituitary, paraventricular nucleus and hippocampus, and a failure to habituate to an open field. Together, these findings point to NRG1 as a potential novel regulator of neuroendocrine responses to stress as well as behavioral reactivity. Copyright © 2010 Elsevier Inc. All rights reserved.

  5. Sex differences in the HPA axis.

    Science.gov (United States)

    Goel, Nirupa; Workman, Joanna L; Lee, Tiffany T; Innala, Leyla; Viau, Victor

    2014-07-01

    The hypothalamic-pituitary-adrenal (HPA) axis is a major component of the systems that respond to stress, by coordinating the neuroendocrine and autonomic responses. Tightly controlled regulation of HPA responses is critical for maintaining mental and physical health, as hyper- and hypo-activity have been linked to disease states. A long history of research has revealed sex differences in numerous components of the HPA stress system and its responses, which may partially form the basis for sex disparities in disease development. Despite this, many studies use male subjects exclusively, while fewer reports involve females or provide direct sex comparisons. The purpose of this article is to present sex comparisons in the functional and molecular aspects of the HPA axis, through various phases of activity, including basal, acute stress, and chronic stress conditions. The HPA axis in females initiates more rapidly and produces a greater output of stress hormones. This review focuses on the interactions between the gonadal hormone system and the HPA axis as the key mediators of these sex differences, whereby androgens increase and estrogens decrease HPA activity in adulthood. In addition to the effects of gonadal hormones on the adult response, morphological impacts of hormone exposure during development are also involved in mediating sex differences. Additional systems impinging on the HPA axis that contribute to sex differences include the monoamine neurotransmitters norepinephrine and serotonin. Diverse signals originating from the brain and periphery are integrated to determine the level of HPA axis activity, and these signals are, in many cases, sex-specific.

  6. Salivary cortisol is related to atherosclerosis of carotid arteries

    NARCIS (Netherlands)

    M.J.H.J. Dekker (Marieke); J.W. Koper (Jan); M.O. van Aken (Maarten); H.A.P. Pols (Huib); A. Hofman (Albert); F.H. de Jong (Frank); C. Kirschbaum (Clemens); J.C.M. Witteman (Jacqueline); S.W.J. Lamberts (Steven); H.W. Tiemeier (Henning)

    2008-01-01

    textabstractBackground: Dysregulation of the hypothalamic-pituitary-adrenal axis has been suggested as an independent risk factor for ischemic heart disease. The aim of our study was to evaluate whether two markers of the hypothalamic-pituitary- adrenal axis activity, the level of salivary cortisol

  7. Fisiopatología de la disfunción gonadal en la Amenorrea Hipotalámica funcional (AHF) y su relación con la activación del eje hipotálamo-hipófiso-adrenal Pathophysiology of gonadal dysfunction in functional Hypothalamic Amenorrhea (FHA) and its relation to activation of the hypothalamic-pituitary-adrenal axis

    OpenAIRE

    León Fiszlejder

    2011-01-01

    La amenorrea hipotalámica funcional (AHF) constituye un proceso secundario de una respuesta de adaptación en mujeres que consumen dietas inadecuadas y presentan modificaciones en la composición corporal de su organismo. Ello origina reacciones hormonales en el hipotálamo destinadas a preservar la homeostasis metabólica. En este proceso de adaptación intervienen un "circuito central" constituido por una red de hormonas hipotalámicas que se interrelacionan con un "circuito periférico" integrado...

  8. Fisiopatología de la disfunción gonadal en la Amenorrea Hipotalámica funcional (AHF) y su relación con la activación del eje hipotálamo-hipófiso-adrenal Pathophysiology of gonadal dysfunction in functional Hypothalamic Amenorrhea (FHA) and its relation to activation of the hypothalamic-pituitary-adrenal axis

    National Research Council Canada - National Science Library

    León Fiszlejder

    2011-01-01

    ... hipotalámicas que se interrelacionan con un "circuito periférico" integrado por la leptina y adiponectina, entre otras adipokinas, y la ghrelina, sintetizada en el tracto gastrointestinal superior...

  9. Fisiopatología de la disfunción gonadal en la Amenorrea Hipotalámica funcional (AHF) y su relación con la activación del eje hipotálamo-hipófiso-adrenal Pathophysiology of gonadal dysfunction in functional Hypothalamic Amenorrhea (FHA) and its relation to activation of the hypothalamic-pituitary-adrenal axis

    OpenAIRE

    León Fiszlejder

    2011-01-01

    La amenorrea hipotalámica funcional (AHF) constituye un proceso secundario de una respuesta de adaptación en mujeres que consumen dietas inadecuadas y presentan modificaciones en la composición corporal de su organismo. Ello origina reacciones hormonales en el hipotálamo destinadas a preservar la homeostasis metabólica. En este proceso de adaptación intervienen un "circuito central" constituido por una red de hormonas hipotalámicas que se interrelacionan con un "circuito periférico" integrado...

  10. Childhood stressful events, HPA axis and anxiety disorders.

    Science.gov (United States)

    Faravelli, Carlo; Lo Sauro, Carolina; Godini, Lucia; Lelli, Lorenzo; Benni, Laura; Pietrini, Francesco; Lazzeretti, Lisa; Talamba, Gabriela Alina; Fioravanti, Giulia; Ricca, Valdo

    2012-02-22

    Anxiety disorders are among the most common of all mental disorders and their pathogenesis is a major topic in psychiatry, both for prevention and treatment. Early stressful life events and alterations of hypothalamic pituitary adrenal (HPA) axis function seem to have a significant role in the onset of anxiety. Existing data appear to support the mediating effect of the HPA axis between childhood traumata and posttraumatic stress disorder. Findings on the HPA axis activity at baseline and after stimuli in panic disordered patients are inconclusive, even if stressful life events may have a triggering function in the development of this disorder. Data on the relationship between stress, HPA axis functioning and obsessive-compulsive disorder (OCD) are scarce and discordant, but an increased activity of the HPA axis is reported in OCD patients. Moreover, normal basal cortisol levels and hyper-responsiveness of the adrenal cortex during a psychosocial stressor are observed in social phobics. Finally, abnormal HPA axis activity has also been observed in generalized anxiety disordered patients. While several hypothesis have attempted to explain these findings over time, currently the most widely accepted theory is that early stressful life events may provoke alterations of the stress response and thus of the HPA axis, that can endure during adulthood, predisposing individuals to develop psychopathology. All theories are reviewed and the authors conclude that childhood life events and HPA abnormalities may be specifically and transnosographically related to all anxiety disorders, as well as, more broadly, to all psychiatric disorders.

  11. Neuroimmunological Responses to Social Isolation

    OpenAIRE

    Ramirez DDS, MSc, PhD, Karol

    2015-01-01

    Objective social isolation and perceived social isolation are psychosocial stressors that may impair the normal functioning of the neuroimmune system. Chronic activation of the neuro-immuno-endocrine communication and the consequent loss of homeostasis may lead to the appearance of pathologies and associated mood disorders. For example, alterations in the hypothalamic-pituitary- adrenal axis and sympathetic nervous system dynamics may account for the observed predisposition to inflammatory di...

  12. Gut Microbiota-brain Axis

    Institute of Scientific and Technical Information of China (English)

    Hong-Xing Wang; Yu-Ping Wang

    2016-01-01

    Objective:To systematically review the updated information about the gut microbiota-brain axis.Data Sources:All articles about gut microbiota-brain axis published up to July 18,2016,were identified through a literature search on PubMed,ScienceDirect,and Web of Science,with the keywords of"gut microbiota","gut-brain axis",and "neuroscience".Study Selection:All relevant articles on gut microbiota and gut-brain axis were included and carefully reviewed,with no limitation of study design.Results:It is well-recognized that gut microbiota affects the brain's physiological,behavioral,and cognitive functions although its precise mechanism has not yet been fully understood.Gut microbiota-brain axis may include gut microbiota and their metabolic products,enteric nervous system,sympathetic and parasympathetic branches within the autonomic nervous system,neural-immune system,neuroendocrine system,and central nervous system.Moreover,there may be five communication routes between gut microbiota and brain,including the gut-brain's neural network,neuroendocrine-hypothalamic-pituitary-adrenal axis,gut immune system,some neurotransmitters and neural regulators synthesized by gut bacteria,and barrier paths including intestinal mucosal barrier and blood-brain barrier.The microbiome is used to define the composition and functional characteristics of gut microbiota,and metagenomics is an appropriate technique to characterize gut microbiota.Conclusions:Gut microbiota-brain axis refers to a bidirectional information network between the gut microbiota and the brain,which may provide a new way to protect the brain in the near future.

  13. Mifepristone Accelerates HPA Axis Recovery in Secondary Adrenal Insufficiency.

    Science.gov (United States)

    Cohan, Pejman

    2016-01-01

    Context. Transient secondary adrenal insufficiency (SAI) is an expected complication following successful adenomectomy of ACTH-secreting pituitary adenomas or unilateral adrenalectomy for cortisol-secreting adrenal adenomas. To date, no pharmacological therapy has been shown to hasten recovery of the hypothalamic-pituitary-adrenal (HPA) axis in this clinical scenario. Case Description. A 33-year-old woman underwent uncomplicated unilateral adrenalectomy for a 3.7 cm cortisol-secreting adrenal adenoma. Postoperatively, she developed SAI and was placed on hydrocortisone 15 mg/day, given in divided doses. In the ensuing six years, the patient's HPA axis failed to recover and she remained corticosteroid-dependent. Quarterly biochemical testing (after withholding hydrocortisone for 18 hours) consistently yielded undetectable serum cortisol and subnormal plasma ACTH levels. While she was on hydrocortisone 15 mg/day, mifepristone was initiated and gradually titrated to a maintenance dose of 600 mg/day after 5 months. Rapid recovery of the HPA axis was subsequently noted with ACTH rising into the supranormal range at 4 months followed by a subsequent rise in cortisol levels into the normal range. After 6 months, the dose of hydrocortisone and mifepristone was lowered and both were ultimately stopped after 8 months. The HPA axis remains normal after an additional 16 months of follow-up. Conclusion. Mifepristone successfully restored the HPA axis in a woman with prolonged secondary adrenal insufficiency (SAI) after adrenalectomy for Cushing's syndrome (CS).

  14. Suppression of the HPA axis during extrahepatic biliary obstruction induces cholangiocyte proliferation in the rat.

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    Quinn, Matthew; Ueno, Yoshiyuki; Pae, Hae Yong; Huang, Li; Frampton, Gabriel; Galindo, Cheryl; Francis, Heather; Horvat, Darijana; McMillin, Matthew; Demorrow, Sharon

    2012-01-01

    Cholestatic patients often present with clinical features suggestive of adrenal insufficiency. In the bile duct-ligated (BDL) model of cholestasis, the hypothalamic-pituitary-adrenal (HPA) axis is suppressed. The consequences of this suppression on cholangiocyte proliferation are unknown. We evaluated 1) HPA axis activity in various rat models of cholestasis and 2) effects of HPA axis modulation on cholangiocyte proliferation. Expression of regulatory molecules of the HPA axis was determined after BDL, partial BDL, and α-naphthylisothiocyanate (ANIT) intoxication. The HPA axis was suppressed by inhibition of hypothalamic corticotropin-releasing hormone (CRH) expression by central administration of CRH-specific Vivo-morpholinos or by adrenalectomy. After BDL, the HPA axis was reactivated by 1) central administration of CRH, 2) systemic ACTH treatment, or 3) treatment with cortisol or corticosterone for 7 days postsurgery. There was decreased expression of 1) hypothalamic CRH, 2) pituitary ACTH, and 3) key glucocorticoid synthesis enzymes in the adrenal glands. Serum corticosterone and cortisol remained low after BDL (but not partial BDL) compared with sham surgery and after 2 wk of ANIT feeding. Experimental suppression of the HPA axis increased cholangiocyte proliferation, shown by increased cytokeratin-19- and proliferating cell nuclear antigen-positive cholangiocytes. Conversely, restoration of HPA axis activity inhibited BDL-induced cholangiocyte proliferation. Suppression of the HPA axis is an early event following BDL and induces cholangiocyte proliferation. Knowledge of the role of the HPA axis during cholestasis may lead to development of innovative treatment paradigms for chronic liver disease.

  15. Gut Microbiota-brain Axis

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    Wang, Hong-Xing; Wang, Yu-Ping

    2016-01-01

    Objective: To systematically review the updated information about the gut microbiota-brain axis. Data Sources: All articles about gut microbiota-brain axis published up to July 18, 2016, were identified through a literature search on PubMed, ScienceDirect, and Web of Science, with the keywords of “gut microbiota”, “gut-brain axis”, and “neuroscience”. Study Selection: All relevant articles on gut microbiota and gut-brain axis were included and carefully reviewed, with no limitation of study design. Results: It is well-recognized that gut microbiota affects the brain's physiological, behavioral, and cognitive functions although its precise mechanism has not yet been fully understood. Gut microbiota-brain axis may include gut microbiota and their metabolic products, enteric nervous system, sympathetic and parasympathetic branches within the autonomic nervous system, neural-immune system, neuroendocrine system, and central nervous system. Moreover, there may be five communication routes between gut microbiota and brain, including the gut-brain's neural network, neuroendocrine-hypothalamic-pituitary-adrenal axis, gut immune system, some neurotransmitters and neural regulators synthesized by gut bacteria, and barrier paths including intestinal mucosal barrier and blood-brain barrier. The microbiome is used to define the composition and functional characteristics of gut microbiota, and metagenomics is an appropriate technique to characterize gut microbiota. Conclusions: Gut microbiota-brain axis refers to a bidirectional information network between the gut microbiota and the brain, which may provide a new way to protect the brain in the near future. PMID:27647198

  16. Circadian genes, the stress axis, and alcoholism.

    Science.gov (United States)

    Sarkar, Dipak K

    2012-01-01

    The body's internal system to control the daily rhythm of the body's functions (i.e., the circadian system), the body's stress response, and the body's neurobiology are highly interconnected. Thus, the rhythm of the circadian system impacts alcohol use patterns; at the same time, alcohol drinking also can alter circadian functions. The sensitivity of the circadian system to alcohol may result from alcohol's effects on the expression of several of the clock genes that regulate circadian function. The stress response system involves the hypothalamus and pituitary gland in the brain and the adrenal glands, as well as the hormones they secrete, including corticotrophin-releasing hormone, adrenocorticotrophic hormone, and glucocorticoids. It is controlled by brain-signaling molecules, including endogenous opioids such as β-endorphin. Alcohol consumption influences the activity of this system and vice versa. Finally, interactions exist between the circadian system, the hypothalamic-pituitary-adrenal axis, and alcohol consumption. Thus, it seems that certain clock genes may control functions of the stress response system and that these interactions are affected by alcohol.

  17. Age of Trauma Onset and HPA Axis Dysregulation Among Trauma-Exposed Youth.

    Science.gov (United States)

    Kuhlman, Kate Ryan; Vargas, Ivan; Geiss, Elisa G; Lopez-Duran, Nestor L

    2015-12-01

    The hypothalamic-pituitary-adrenal axis (HPA axis) is a pathway through which childhood trauma may increase risk for negative health outcomes. The HPA axis is sensitive to stress throughout development; however, few studies have examined whether timing of exposure to childhood trauma is related to differences in later HPA axis functioning. Therefore, we examined the association between age of first trauma and HPA axis functioning among adolescents, and whether these associations varied by sex. Parents of 97 youth (aged 9-16 years) completed the Early Trauma Inventory (ETI), and youth completed the Socially-Evaluated Cold-Pressor Task (SECPT). We measured salivary cortisol response to the SECPT, the cortisol awakening response, and diurnal regulation at home across 2 consecutive weekdays. Exposure to trauma during infancy related to delayed cortisol recovery from peak responses to acute stress, d = 0.23 to 0.42. Timing of trauma exposure related to diverging patterns of diurnal cortisol regulation for males, d = 0.55, and females, d = 0.57. Therefore, the HPA axis may be susceptible to developing acute stress dysregulation when exposed to trauma during infancy, whereas the consequences within circadian cortisol regulation may occur in the context of later trauma exposure and vary by sex. Further investigations are warranted to characterize HPA axis sensitivity to exposure to childhood trauma across child development.

  18. Seizure-induced disinhibition of the HPA axis increases seizure susceptibility.

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    O'Toole, Kate K; Hooper, Andrew; Wakefield, Seth; Maguire, Jamie

    2014-01-01

    Stress is the most commonly reported precipitating factor for seizures. The proconvulsant actions of stress hormones are thought to mediate the effects of stress on seizure susceptibility. Interestingly, epileptic patients have increased basal levels of stress hormones, including corticotropin-releasing hormone (CRH) and corticosterone, which are further increased following seizures. Given the proconvulsant actions of stress hormones, we proposed that seizure-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis may contribute to future seizure susceptibility. Consistent with this hypothesis, our data demonstrate that pharmacological induction of seizures in mice with kainic acid or pilocarpine increases circulating levels of the stress hormone, corticosterone, and exogenous corticosterone administration is sufficient to increase seizure susceptibility. However, the mechanism(s) whereby seizures activate the HPA axis remain unknown. Here we demonstrate that seizure-induced activation of the HPA axis involves compromised GABAergic control of CRH neurons, which govern HPA axis function. Following seizure activity, there is a collapse of the chloride gradient due to changes in NKCC1 and KCC2 expression, resulting in reduced amplitude of sIPSPs and even depolarizing effects of GABA on CRH neurons. Seizure-induced activation of the HPA axis results in future seizure susceptibility which can be blocked by treatment with an NKCC1 inhibitor, bumetanide, or blocking the CRH signaling with Antalarmin. These data suggest that compromised GABAergic control of CRH neurons following an initial seizure event may cause hyperexcitability of the HPA axis and increase future seizure susceptibility.

  19. The HPA axis and ethanol: a synthesis of mathematical modelling and experimental observations.

    Science.gov (United States)

    Čupić, Željko; Stanojević, Ana; Marković, Vladimir M; Kolar-Anić, Ljiljana; Terenius, Lars; Vukojević, Vladana

    2016-05-18

    Stress and alcohol use are interrelated-stress contributes to the initiation and upholding of alcohol use and alcohol use alters the way we perceive and respond to stress. Intricate mechanisms through which ethanol alters the organism's response to stress remain elusive. We have developed a stoichiometric network model to succinctly describe neurochemical transformations underlying the stress response axis and use numerical simulations to model ethanol effects on complex daily changes of blood levels of cholesterol, 6 peptide and 8 steroid hormones. Modelling suggests that ethanol alters the dynamical regulation of hypothalamic-pituitary-adrenal (HPA) axis activity by affecting the amplitude of ultradian oscillations of HPA axis hormones, which defines the threshold with respect to which the response to stress is being set. These effects are complex-low/moderate acute ethanol challenge (8 mM) increases instantaneous CORT levels and the amplitude of ultradian CORT oscillations in a dose-dependent manner, affecting the HPA axis activity also during the following day(s). Chronic exposure to ethanol qualitatively changes the HPA axis dynamics, whereas ethanol at intoxicating levels shuts down this dynamic regulation mechanism. Mathematical modelling gives a quantitative biology-based framework that can be used for predicting how the integral HPA axis response is perturbed by alcohol.

  20. Early calibration of the HPA axis by maternal psychopathology.

    Science.gov (United States)

    Laurent, Heidemarie

    2017-02-01

    Given the central role of stress-responsive neurophysiology in mental and physical health, it is important to understand how particular patterns of stress responsivity may become entrained by the early caregiving environment. In this study we investigated links between maternal depression and anxiety symptom profiles and within-infant development of hypothalamic-pituitary-adrenal (HPA) axis responses from 6 to 18 months of life. Associations with infant cognitive and social-emotional development were also tested to gauge the adjustment implications of HPA response trajectories. Mothers from a low-income community sample reported their symptoms at 3, 6, 12, and 18 months postnatal, and infants engaged in interpersonal stress tasks at 6, 12, and 18 months. Four saliva samples were taken at each time to assess cortisol responses, and a developmental screener at 18 months provided an index of infant adjustment. Multilevel modeling results revealed an association between maternal symptoms and infant HPA axis sensitization-i.e., a higher cortisol reactivity slope that increased over time. In particular, early (3-month) depression symptoms among mothers who had crossed a diagnostic threshold for major depressive disorder predicted this pattern of response, which in turn related to poorer infant developmental outcomes. Results are considered in terms of adaptive calibration of stress response systems, which may come at a cost to individual psychosocial functioning.

  1. Relationships between psychological distress, coping styles, and HPA axis reactivity in healthy adults.

    Science.gov (United States)

    Hori, Hiroaki; Ozeki, Yuji; Teraishi, Toshiya; Matsuo, Junko; Kawamoto, Yumiko; Kinoshita, Yukiko; Suto, Shiho; Terada, Sumio; Higuchi, Teruhiko; Kunugi, Hiroshi

    2010-10-01

    Psychological distress and coping styles have been suggested to relate to altered function in the hypothalamic-pituitary-adrenal (HPA) axis, although there remains much to be understood about their relationships. High and low cortisol levels (or reactivity) both represent HPA axis dysfunction, with accumulated evidence suggesting that they are linked to different types of psychopathology. The dexamethasone (DEX)/corticotropin-releasing hormone (CRH) test has been extensively used to identify HPA axis abnormalities in various psychiatric conditions including mood disorders; however, the possible associations of psychological distress and coping styles with HPA axis function have not been well documented using this test. Here, we examined the relationships of HPA axis reactivity as measured by the DEX/CRH test with subjectively perceived psychological distress and coping styles, both of which were assessed with self-report questionnaires, in 121 healthy volunteers. Subjects were divided into three groups by the cortisol suppression pattern, namely the incomplete-suppressors (DST-Cortisol ≥ 5 μg/dL or DEX/CRH-Cortisol ≥ 5 μg/dL), moderate-suppressors (DST-Cortisol psychological distress. Copyright © 2010 Elsevier Ltd. All rights reserved.

  2. A users guide to HPA axis research.

    Science.gov (United States)

    Spencer, Robert L; Deak, Terrence

    2016-11-18

    Glucocorticoid hormones (cortisol and corticosterone - CORT) are the effector hormones of the hypothalamic-pituitary-adrenal (HPA) axis neuroendocrine system. CORT is a systemic intercellular signal whose level predictably varies with time of day and dynamically increases with environmental and psychological stressors. This hormonal signal is utilized by virtually every cell and physiological system of the body to optimize performance according to circadian, environmental and physiological demands. Disturbances in normal HPA axis activity profiles are associated with a wide variety of physiological and mental health disorders. Despite numerous studies to date that have identified molecular, cellular and systems-level glucocorticoid actions, new glucocorticoid actions and clinical status associations continue to be revealed at a brisk pace in the scientific literature. However, the breadth of investigators working in this area poses distinct challenges in ensuring common practices across investigators, and a full appreciation for the complexity of a system that is often reduced to a single dependent measure. This Users Guide is intended to provide a fundamental overview of conceptual, technical and practical knowledge that will assist individuals who engage in and evaluate HPA axis research. We begin with examination of the anatomical and hormonal components of the HPA axis and their physiological range of operation. We then examine strategies and best practices for systematic manipulation and accurate measurement of HPA axis activity. We feature use of experimental methods that will assist with better understanding of CORT's physiological actions, especially as those actions impact subsequent brain function. This research approach is instrumental for determining the mechanisms by which alterations of HPA axis function may contribute to pathophysiology.

  3. Prenatal xenobiotic exposure and intrauterine hypothalamus-pituitary-adrenal axis programming alteration.

    Science.gov (United States)

    Zhang, Chong; Xu, Dan; Luo, Hanwen; Lu, Juan; Liu, Lian; Ping, Jie; Wang, Hui

    2014-11-05

    The hypothalamic-pituitary-adrenal (HPA) axis is one of the most important neuroendocrine axes and plays an important role in stress defense responses before and after birth. Prenatal exposure to xenobiotics, including environmental toxins (such as smoke, sulfur dioxide and carbon monoxide), drugs (such as synthetic glucocorticoids), and foods and beverage categories (such as ethanol and caffeine), affects fetal development indirectly by changing the maternal status or damaging the placenta. Certain xenobiotics (such as caffeine, ethanol and dexamethasone) may also affect the fetus directly by crossing the placenta into the fetus due to their lipophilic properties and lower molecular weights. All of these factors probably result in intrauterine programming alteration of the HPA axis, which showed a low basal activity but hypersensitivity to chronic stress. These alterations will, therefore, increase the susceptibility to adult neuropsychiatric (such as depression and schizophrenia) and metabolic diseases (such as hypertension, diabetes and non-alcoholic fatty liver disease). The "over-exposure of fetuses to maternal glucocorticoids" may be the main initiation factor by which the fetal HPA axis programming is altered. Meantime, xenobiotics can directly induce abnormal epigenetic modifications and expression on the important fetal genes (such as hippocampal glucocorticoid receptor, adrenal steroidogenic acute regulatory protein, et al) or damage by in situ oxidative metabolism of fetal adrenals, which may also be contributed to the programming alteration of fetal HPA axis.

  4. Overnight suppression of HPA axis after mineraolocorticoid receptor stimulation: A sleep endocrine study.

    Science.gov (United States)

    Demiralay, Cüneyt; Agorastos, Agorastos; Jahn, Holger; Kellner, Michael; Yassouridis, Alexander; Wiedemann, Klaus

    2015-05-30

    Nocturnal hyperactivity of hypothalamic-pituitary-adrenal axis (HPA) indicates decreased feedback inhibition with stress-related conditions such as major depression and sleep disorders. To characterize the role of mineralocorticoid (MR) in regulation of HPA axis activity during nocturnal sleep and involvement in sleep architecture, we investigated sleep endocrine effects of the MR agonist fludrocortisone in healthy men after pretreatment with metyrapone to minimize the impact of endogenous cortisol. Subjects (n=8) were treated on three occasions in a single-blinded design in random order with a) metyrapone, b) fludrocortisone after metyrapone, and c) placebo. Polysomnography was recorded and blood samples were drawn for determination of adrenocorticotropic hormone (ACTH) and cortisol during the entire night. After metyrapone administration ACTH was significantly enhanced, while overall nocturnal cortisol secretion remained largely unchanged. Whereas administration of fludrocortisone induced a significant inhibitory effect on basal ACTH and cortisol secretion, no considerable effects on sleep pattern were detectable. While the involvement of MR in sleep regulation needs further study, endocrine findings underline the role of MR in tonic regulation of HPA axis during nocturnal sleep and demonstrate the ability of fludrocortisone to further suppress HPA axis activity overnight. Additional studies would be required to evaluate endocrine and clinical fludrocortisone effects in depressive patients showing HPA hyperactivity.

  5. Dynamics of the HPA axis and inflammatory cytokines: Insights from mathematical modeling.

    Science.gov (United States)

    Malek, Hamed; Ebadzadeh, Mohammad Mehdi; Safabakhsh, Reza; Razavi, Alireza; Zaringhalam, Jalal

    2015-12-01

    In the work presented here, a novel mathematical model was developed to explore the bi-directional communication between the hypothalamic-pituitary-adrenal (HPA) axis and inflammatory cytokines in acute inflammation. The dynamic model consists of five delay differential equations 5D for two main pro-inflammatory cytokines (TNF-α and IL-6) and two hormones of the HPA axis (ACTH and cortisol) and LPS endotoxin. The model is an attempt to increase the understanding of the role of primary hormones and cytokines in this complex relationship by demonstrating the influence of different organs and hormones in the regulation of the inflammatory response. The model captures the main qualitative features of cytokine and hormone dynamics when a toxic challenge is introduced. Moreover, in this work a new simple delayed model of the HPA axis is introduced which supports the understanding of the ultradian rhythm of HPA hormones both in normal and infection conditions. Through simulations using the model, the role of key inflammatory cytokines and cortisol in transition from acute to persistent inflammation through stability analysis is investigated. Also, by employing a Markov chain Monte Carlo (MCMC) method, parameter uncertainty and the effects of parameter variations on each other are analyzed. This model confirms the important role of the HPA axis in acute and prolonged inflammation and can be a useful tool in further investigation of the role of stress on the immune response to infectious diseases.

  6. Probiotics normalize the gut-brain-microbiota axis in immunodeficient mice.

    Science.gov (United States)

    Smith, Carli J; Emge, Jacob R; Berzins, Katrina; Lung, Lydia; Khamishon, Rebecca; Shah, Paarth; Rodrigues, David M; Sousa, Andrew J; Reardon, Colin; Sherman, Philip M; Barrett, Kim E; Gareau, Mélanie G

    2014-10-15

    The gut-brain-microbiota axis is increasingly recognized as an important regulator of intestinal physiology. Exposure to psychological stress causes activation of the hypothalamic-pituitary-adrenal (HPA) axis and causes altered intestinal barrier function, intestinal dysbiosis, and behavioral changes. The primary aim of this study was to determine whether the effects of psychological stress on intestinal physiology and behavior, including anxiety and memory, are mediated by the adaptive immune system. Furthermore, we wanted to determine whether treatment with probiotics would normalize these effects. Here we demonstrate that B and T cell-deficient Rag1(-/-) mice displayed altered baseline behaviors, including memory and anxiety, accompanied by an overactive HPA axis, increased intestinal secretory state, dysbiosis, and decreased hippocampal c-Fos expression. Both local (intestinal physiology and microbiota) and central (behavioral and hippocampal c-Fos) changes were normalized by pretreatment with probiotics, indicating an overall benefit on health conferred by changes in the microbiota, independent of lymphocytes. Taken together, these findings indicate a role for adaptive immune cells in maintaining normal intestinal and brain health in mice and show that probiotics can overcome this immune-mediated deficit in the gut-brain-microbiota axis. Copyright © 2014 the American Physiological Society.

  7. Evidence for a Role of Adolescent Endocannabinoid Signaling in Regulating HPA Axis Stress Responsivity and Emotional Behavior Development.

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    Lee, Tiffany T-Y; Gorzalka, Boris B

    2015-01-01

    Adolescence is a period characterized by many distinct physical, behavioral, and neural changes during the transition from child- to adulthood. In particular, adolescent neural changes often confer greater plasticity and flexibility, yet with this comes the potential for heightened vulnerability to external perturbations such as stress exposure or recreational drug use. There is substantial evidence to suggest that factors such as adolescent stress exposure have longer lasting and sometimes more deleterious effects on an organism than stress exposure during adulthood. Moreover, the adolescent neuroendocrine response to stress exposure is different from that of adults, suggesting that further maturation of the adolescent hypothalamic-pituitary-adrenal (HPA) axis is required. The endocannabinoid (eCB) system is a potential candidate underlying these age-dependent differences given that it is an important regulator of the adult HPA axis and neuronal development. Therefore, this review will focus on (1) the functionality of the adolescent HPA axis, (2) eCB regulation of the adult HPA axis, (3) dynamic changes in eCB signaling during the adolescent period, (4) the effects of adolescent stress exposure on the eCB system, and (5) modulation of HPA axis activity and emotional behavior by adolescent cannabinoid treatment. Collectively, the emerging picture suggests that the eCB system mediates interactions between HPA axis stress responsivity, emotionality, and maturational stage. These findings may be particularly relevant to our understanding of the development of affective disorders and the risks of adolescent cannabis consumption on emotional health and stress responsivity.

  8. Hypothalamic-Pituitary-Adrenal and Sympathetic Nervous System Activity and Children's Behavioral Regulation

    Science.gov (United States)

    Lisonbee, Jared A.; Pendry, Patricia; Mize, Jacquelyn; Gwynn, Eugenia Parrett

    2010-01-01

    Self-regulation ability is an important component of children's academic success. Physiological reactivity may relate to brain activity governing attention and behavioral regulation. Saliva samples collected from 186 preschool children (101 boys, mean age = 53 months, 34% minority) before and after a series of mildly challenging games and again 30…

  9. Hypothalamic-Pituitary-Adrenal and Sympathetic Nervous System Activity and Children's Behavioral Regulation

    Science.gov (United States)

    Lisonbee, Jared A.; Pendry, Patricia; Mize, Jacquelyn; Gwynn, Eugenia Parrett

    2010-01-01

    Self-regulation ability is an important component of children's academic success. Physiological reactivity may relate to brain activity governing attention and behavioral regulation. Saliva samples collected from 186 preschool children (101 boys, mean age = 53 months, 34% minority) before and after a series of mildly challenging games and again 30…

  10. Hypothalamic-Pituitary-Adrenal Suppression and Iatrogenic Cushing's Syndrome as a Complication of Epidural Steroid Injections

    Directory of Open Access Journals (Sweden)

    Joyce Leary

    2013-01-01

    Full Text Available Epidural steroid injections are well accepted as a treatment for radicular back pain in appropriate candidates. While overall incidence of systemic side effects has not been well established, at least five biochemically proven cases of iatrogenic Cushing's Syndrome have been reported as complications of epidural steroid treatment. We present an additional case of iatrogenic Cushing's Syndrome and adrenal suppression in a middle-aged woman who received three epidural steroid injections over a four-month period. We review this case in the context of previous cases and discuss diagnostic and management issues.

  11. Burnout Is Associated with Reduced Parasympathetic Activity and Reduced HPA Axis Responsiveness, Predominantly in Males

    Directory of Open Access Journals (Sweden)

    Wieke de Vente

    2015-01-01

    Full Text Available There is mounting evidence that burnout is a risk factor for cardiovascular disease (CVD. Stress-related dysregulation of the sympathetic and parasympathetic system and the hypothalamic pituitary adrenal (HPA axis may explain the enhanced risk for CVD. To test this hypothesis, 55 patients (34 males and 21 females with burnout on sickness absence and 40 healthy participants (16 males and 24 females were exposed to a psychosocial stressor consisting of mental arithmetic and public speech. Physiological variables (i.e., blood pressure, heart rate, cardiac output, vascular resistance, cortisol, and alpha-amylase were measured. Basal levels, reactivity, and recovery were compared between groups. In male patients, baseline systolic blood pressure was higher, whereas basal alpha-amylase and cortisol reactivity were lower than in healthy males. In female patients, a tendency for lower basal cortisol was found as compared to healthy females. Furthermore, reduced basal heart rate variability and a trend for elevated basal cardiac output were observed in both male and female patients. Burnout is characterised by dysregulation of the sympathetic and parasympathetic system and the HPA axis, which was more pronounced in males than in females. This study further supports burnout as being a risk factor for CVD through dysregulation of the sympathetic and parasympathetic system and the HPA axis.

  12. HPA-axis hormone modulation of stress response circuitry activity in women with remitted major depression.

    Science.gov (United States)

    Holsen, L M; Lancaster, K; Klibanski, A; Whitfield-Gabrieli, S; Cherkerzian, S; Buka, S; Goldstein, J M

    2013-10-10

    Decades of clinical and basic research indicate significant links between altered hypothalamic-pituitary-adrenal (HPA)-axis hormone dynamics and major depressive disorder (MDD). Recent neuroimaging studies of MDD highlight abnormalities in stress response circuitry regions which play a role in the regulation of the HPA-axes. However, there is a dearth of research examining these systems in parallel, especially as related to potential trait characteristics. The current study addresses this gap by investigating neural responses to a mild visual stress challenge with real-time assessment of adrenal hormones in women with MDD in remission and controls. Fifteen women with recurrent MDD in remission (rMDD) and 15 healthy control women were scanned on a 3T Siemens MR scanner while viewing neutral and negative (stress-evoking) stimuli. Blood samples were obtained before, during, and after scanning for the measurement of HPA-axis hormone levels. Compared to controls, rMDD women demonstrated higher anxiety ratings, increased cortisol levels, and hyperactivation in the amygdala and hippocampus, pHPA-axis hormone dynamics on hyperactivity in stress response circuitry regions elicited by a well-validated stress paradigm in women with recurrent MDD in remission.

  13. Influence of hypothalamic IL-6/gp130 receptor signaling on the HPA axis response to chronic stress.

    Science.gov (United States)

    Girotti, Milena; Donegan, Jennifer J; Morilak, David A

    2013-07-01

    Abnormal basal activity and stress-evoked reactivity of the hypothalamic-pituitary-adrenal (HPA) axis are often seen in depression, implicating HPA axis dysfunction as a potentially causative or exacerbating factor. Chronic stress is also a factor in depression, but it is not known what may underlie the shift from adaptive to maladaptive HPA activity over the course of chronic stress. Interleukin 6 (IL-6), a stress-inducible cytokine that signals through gp130 and IL-6Rα receptors to activate the JAK/STAT3 signaling cascade, is elevated in some subtypes of depression, and may have a modulatory effect on HPA activation, raising the possibility that IL-6 contributes to depression through effects on the HPA axis. In this study, we examined the effects of three different stress modalities, acute footshock, chronic intermittent cold (CIC) stress and chronic unpredictable stress (CUS) on IL-6 signaling in the hypothalamus. We also investigated whether IL-6 modulates the HPA response to chronic stress, by blocking IL-6 signaling in the brain during CIC stress using either a neutralizing antibody or an inhibitor of STAT3 phosphorylation. We show that IL-6 and STAT3 in the hypothalamus are activated in response to footshock and CUS. We also found that basal IL-6 signaling through the JAK/STAT3 pathway is required for the sustained CORT response to chronic, but not acute, cold stress and therefore is a potential determinant of plasticity in the HPA axis specifically during chronic stress exposure.

  14. Bicuculline, a GABAA-receptor antagonist, blocked HPA axis activation induced by ghrelin under an acute stress.

    Science.gov (United States)

    Gastón, M S; Cid, M P; Salvatierra, N A

    2017-03-01

    Ghrelin is a peptide of 28 amino acids with a homology between species, which acts on the central nervous system to regulate different actions, including the control of growth hormone secretion and metabolic regulation. It has been suggested that central ghrelin is a mediator of behavior linked to stress responses and induces anxiety in rodents and birds. Previously, we observed that the anxiogenic-like behavior induced by ghrelin injected into the intermediate medial mesopallium (IMM) of the forebrain was blocked by bicuculline (a GABAA receptor competitive antagonist) but not by diazepam (a GABAA receptor allosteric agonist) in neonatal meat-type chicks (Cobb). Numerous studies have indicated that hypothalamic-pituitary-adrenal (HPA) axis activation mediates the response to stress in mammals and birds. However, it is still unclear whether this effect of ghrelin is associated with HPA activation. Therefore, we investigated whether anxiety behavior induced by intra-IMM ghrelin and mediated through GABAA receptors could be associated with HPA axis activation in the neonatal chick. In the present study, in an Open Field test, intraperitoneal bicuculline methiodide blocked anxiogenic-like behavior as well as the increase in plasma ACTH and corticosterone levels induced by ghrelin (30pmol) in neonatal chicks. Moreover, we showed for the first time that a competitive antagonist of GABAA receptor suppressed the HPA axis activation induced by an anxiogenic dose of ghrelin. These results show that the anxiogenic ghrelin action involves the activation of the HPA axis, with a complex functional interaction with the GABAA receptor.

  15. Long-term effects of repeated maternal separation and ethanol intake on HPA axis responsiveness in adult rats.

    Science.gov (United States)

    Odeon, María Mercedes; Yamauchi, Laura; Grosman, Mauricio; Acosta, Gabriela Beatriz

    2017-02-15

    It has been shown that early life manipulations produce behavioral, neural, and hormonal effects. The long term consequences of repeated maternal separation (RMS) plus cold stress and ethanol intake were evaluated during adolescence and adult rats on hypothalamic-pituitary-adrenal (HPA) axis in male adult Wistar rats. RMS+ cold stress was applied from postnatal day (PD) 2 in which the pups were separated from their mothers and exposed to cold stress (4°C) 1h per day for 20days; controls remained with their mothers. Then they were exposed to either voluntary ethanol (6%) or dextrose (1%) intake for 7days: PD22-29 and PD59-66. Half of the animals were sacrificed, while the others were exposed to acute stress (AS) for 2h and then they were killed. RMS+ cold stress: a) increased voluntary ethanol intake in adolescent and adult rats; b) reduced protein expression (Western measurements) in corticotropin-releasing hormone (CRH) in hypothalamus (Hyp) and mineralocorticoid receptor (MR) in hippocampus (Hic) while increased glucocorticoid receptor (GR) in Hic; c) decreased plasmatic levels of adrenocorticotropic hormone (ACTH) and increased corticosterone (COR) levels in HPA axis, d) adult rats exposure a new AS incremented ACTH and COR levels. However, this modification did not alter the HPA axis capacity to respond to a new type of stressor. These results demonstrate the consequences of early life stress on the vulnerability of ethanol consumption and HPA axis responsiveness to a stressor in adult rats.

  16. Is Dysregulation of the HPA-Axis a Core Pathophysiology Mediating Co-Morbid Depression in Neurodegenerative Diseases?

    Science.gov (United States)

    Du, Xin; Pang, Terence Y

    2015-01-01

    There is increasing evidence of prodromal manifestation of neuropsychiatric symptoms in a variety of neurodegenerative diseases such as Parkinson's disease (PD) and Huntington's disease (HD). These affective symptoms may be observed many years before the core diagnostic symptoms of the neurological condition. It is becoming more apparent that depression is a significant modifying factor of the trajectory of disease progression and even treatment outcomes. It is therefore crucial that we understand the potential pathophysiologies related to the primary condition, which could contribute to the development of depression. The hypothalamic-pituitary-adrenal (HPA)-axis is a key neuroendocrine signaling system involved in physiological homeostasis and stress response. Disturbances of this system lead to severe hormonal imbalances, and the majority of such patients also present with behavioral deficits and/or mood disorders. Dysregulation of the HPA-axis is also strongly implicated in the pathology of major depressive disorder. Consistent with this, antidepressant drugs, such as the selective serotonin reuptake inhibitors have been shown to alter HPA-axis activity. In this review, we will summarize the current state of knowledge regarding HPA-axis pathology in Alzheimer's, PD and HD, differentiating between prodromal and later stages of disease progression when evidence is available. Both clinical and preclinical evidence will be examined, but we highlight animal model studies as being particularly useful for uncovering novel mechanisms of pathology related to co-morbid mood disorders. Finally, we purpose utilizing the preclinical evidence to better inform prospective, intervention studies.

  17. Patient specific modeling of the HPA axis related to clinical diagnosis of depression.

    Science.gov (United States)

    Bangsgaard, Elisabeth O; Ottesen, Johnny T

    2016-11-02

    A novel model of the hypothalamic-pituitary-adrenal axis is presented. The axis is an endocrine system responsible for coping with stress and it is likely to be involved in depression. The dynamics of the system is studied and existence, uniqueness and positivity of the solution and the existence of an attracting trapping region are proved. The model is calibrated and compared to data for healthy and depressed subjects. A sensitivity analysis resulting in a set of identifiable physiological parameters is provided. A subset is selected for parameter estimation and a reduced version of the model is stated and an approximated version is discussed. The model is physiologically based, thus parameters are representative for gland functions or elimination processes. Hence the model may be used for pointing out pathologies by parameter estimation and hypothesis testing whereby it may be used as an objective and refined method for diagnosing depression and suggesting individual treatment protocols. Finally, the method may inspire pharmaceutical companies to develop target specific psychopharmaca for more effective and individual treatment.

  18. Mitigating HPA Axis Dysregulation Associated With Placement Changes in Foster Care

    Science.gov (United States)

    Fisher, Philip A.; Van Ryzin, Mark J.; Gunnar, Megan R.

    2012-01-01

    Summary Maltreated foster children often exhibit alterations in diurnal hypothalamic-pituitary-adrenal (HPA) axis activity that are characterized by lower cortisol levels upon waking and smaller declines in morning-to-evening cortisol levels. Previous research has shown that this dysregulated pattern is associated with high caregiver stress levels over the course of foster care placements. In contrast, therapeutic interventions that emphasize consistent and responsive caregiving have been associated with more regulated cortisol rhythms. In this paper, two related issues were explored: whether placement changes (i.e., moving between foster homes or from a foster home to a permanent placement) were associated with more blunted daily cortisol rhythms and whether a caregiver-based intervention exerted a protective effect in this context. Because the intervention program has components specifically designed to prepare foster children for placement changes and to maintain consistent parenting techniques despite them, a prevention effect on HPA axis dysregulation during placement changes was hypothesized. The results of linear mixed modeling analyses showed that placement changes predicted dysregulation in cortisol rhythms in the regular foster care group but not in the intervention foster care group. These findings are discussed in terms of implications for child welfare policy and practice. PMID:20888698

  19. Aging and the HPA axis: Stress and resilience in older adults.

    Science.gov (United States)

    Gaffey, Allison E; Bergeman, C S; Clark, Lee Anna; Wirth, Michelle M

    2016-09-01

    Hypothalamic-pituitary-adrenal (HPA) axis function may change over the course of aging, and altered diurnal or stress-induced secretion of the hormone cortisol could predispose older adults to negative health outcomes. We propose that psychological resilience may interact with diurnal cortisol to affect health outcomes later in life. Emotion regulation and social support are two constructs that contribute to resilience and exhibit age-specific patterns in older adults. Determining how the use of resilience resources interacts with age-related diurnal cortisol will improve our understanding of the pathways between stress, resilience, and well-being. In this review, we assess published studies evaluating diurnal cortisol in older adults to better understand differences in their HPA axis functioning. Evidence thus far suggests that diurnal cortisol may increase with age, although cross-sectional studies limit the conclusions that can be drawn. We also review extant evidence connecting age-specific signatures of emotion regulation and social support with diurnal cortisol. Conclusions are used to propose a preliminary model demonstrating how resilience resources may modulate the effects of cortisol on health in aging.

  20. The weight of stigma: Cortisol reactivity to manipulated weight stigma

    National Research Council Canada - National Science Library

    Himmelstein, Mary S; Incollingo Belsky, Angela C; Tomiyama, A. Janet

    2015-01-01

    .... The psychological and physiological consequences of weight stigma remain understudied. This study examined the effects of experimentally manipulated weight stigma on the stress-responsive hypothalamic-pituitary-adrenal axis (HPA...

  1. Antidepressant use and salivary cortisol in depressive and anxiety disorders

    NARCIS (Netherlands)

    Manthey, Leonie; Leeds, Caroline; Giltay, Erik J.; van Veen, Tineke; Vreeburg, Sophie A.; Penninx, Brenda W. J. H.; Zitman, Frans G.

    Antidepressants are an effective treatment for depressive and anxiety disorders. Those disorders are frequently accompanied by heightened cortisol levels. Antidepressants may affect hypothalamic-pituitary-adrenal axis functioning, the alteration of which could be partially responsible for treatment

  2. Permanent upregulation of hippocampal mineralocorticoid receptors after neonatal administration of ACTH-(4-9) analog ORG 2766 in rats

    NARCIS (Netherlands)

    Nyakas, C; Felszeghy, K; Bohus, B; Luiten, PGM

    1997-01-01

    The development of brain corticosteroid receptors may be permanently modified by perinatal hormone treatments, in particular by hormones of the hypothalamic-pituitary-adrenal axis. Changes in binding characteristics of corticosteroid receptors were investigated in rats treated subcutaneously with 1

  3. Antidepressant use and salivary cortisol in depressive and anxiety disorders

    NARCIS (Netherlands)

    Manthey, Leonie; Leeds, Caroline; Giltay, Erik J.; van Veen, Tineke; Vreeburg, Sophie A.; Penninx, Brenda W. J. H.; Zitman, Frans G.

    2011-01-01

    Antidepressants are an effective treatment for depressive and anxiety disorders. Those disorders are frequently accompanied by heightened cortisol levels. Antidepressants may affect hypothalamic-pituitary-adrenal axis functioning, the alteration of which could be partially responsible for treatment

  4. Novel molecular events associated with altered steroidogenesis induced by exposure to atrazine in the intact and castrate male rat

    Science.gov (United States)

    Toxicology is increasingly focused on molecular events comprising adverse outcome pathways. Atrazine activates the hypothalamic-pituitary adrenal axis, but relationships to gonadal alterations are unknown. We characterized hormone profiles and adrenal (intact and castrate) and te...

  5. Role of anxiety in the pathophysiology of irritable bowel syndrome: importance of the amygdala

    National Research Council Canada - National Science Library

    Myers, Brent; Greenwood-Van Meerveld, Beverley

    2009-01-01

    .... The amygdala is an important structure for regulating anxiety with the central nucleus of the amygdala facilitating the activation of the hypothalamic-pituitary-adrenal axis and the autonomic nervous...

  6. Novel molecular events associated with altered steroidogenesis induced by exposure to atrazine in the intact and castrate male rat

    Science.gov (United States)

    Toxicology is increasingly focused on molecular events comprising adverse outcome pathways. Atrazine activates the hypothalamic-pituitary adrenal axis, but relationships to gonadal alterations are unknown. We characterized hormone profiles and adrenal (intact and castrate) and te...

  7. Adaptogens stimulate neuropeptide y and hsp72 expression and release in neuroglia cells

    National Research Council Canada - National Science Library

    Panossian, Alexander; Wikman, Georg; Kaur, Punit; Asea, Alexzander

    2012-01-01

    The beneficial stress-protective effect of adaptogens is related to the regulation of homeostasis via mechanisms of action associated with the hypothalamic-pituitary-adrenal axis and the regulation...

  8. Mathematical modeling of light-mediated HPA axis activity and downstream implications on the entrainment of peripheral clock genes.

    Science.gov (United States)

    Mavroudis, Panteleimon D; Corbett, Siobhan A; Calvano, Steven E; Androulakis, Ioannis P

    2014-10-15

    In this work we propose a semimechanistic model that describes the photic signal transduction to the hypothalamic-pituitary-adrenal (HPA) axis that ultimately regulates the synchronization of peripheral clock genes (PCGs). Our HPA axis model predicts that photic stimulation induces a type-1 phase response curve to cortisol's profile with increased cortisol sensitivity to light exposure in its rising phase, as well as the shortening of cortisol's period as constant light increases (Aschoff's first rule). Furthermore, our model provides insight into cortisol's phase and amplitude dependence on photoperiods and reveals that cortisol maintains highest amplitude variability when it is entrained by a balanced schedule of light and dark periods. Importantly, by incorporating the links between HPA axis and PCGs we were able to investigate how cortisol secretion impacts the entrainment of a population of peripheral cells and show that disrupted light schedules, leading to blunted cortisol secretion, fail to synchronize a population of PCGs which further signifies the loss of circadian rhythmicity in the periphery of the body.

  9. Association, haplotype, and gene-gene interactions of the HPA axis genes with suicidal behaviour in affective disorders.

    Science.gov (United States)

    Leszczyńska-Rodziewicz, Anna; Szczepankiewicz, Aleksandra; Pawlak, Joanna; Dmitrzak-Weglarz, Monika; Hauser, Joanna

    2013-01-01

    Family twin and adoption studies have noted the heritability of specific biological factors that influence suicidal behaviour. Exposure to stress is one of the factors that strongly contribute to suicide attempts. The biological response to stress involves the hypothalamic-pituitary-adrenal axis (HPA). Therefore, we found it interesting to study polymorphisms of genes involved in the HPA axis (CRHR1, NR3C1, and AVPBR1). The study was performed on 597 patients, 225 of whom had a history of suicide attempts. We did not observe any significant differences in the studied polymorphisms between the group of patients with a history of suicide attempts and the control subjects. Our haplotype analysis of the AVPR1b gene revealed an association between the GCA haplotype and suicide attempts; however, this association was not significant after correcting for multiple testing. We did not observe any other association in haplotype and MDR analysis. We report here a comprehensive analysis of the HPA axis genes and a lack of association for genetic variations regarding the risk of suicide attempts in affective disorder patients. Nonetheless, the inconsistencies with the previously published results indicate the importance of the further investigation of these polymorphisms with respect to the risk of suicide attempts.

  10. Association, Haplotype, and Gene-Gene Interactions of the HPA Axis Genes with Suicidal Behaviour in Affective Disorders

    Directory of Open Access Journals (Sweden)

    Anna Leszczyńska-Rodziewicz

    2013-01-01

    Full Text Available Family twin and adoption studies have noted the heritability of specific biological factors that influence suicidal behaviour. Exposure to stress is one of the factors that strongly contribute to suicide attempts. The biological response to stress involves the hypothalamic-pituitary-adrenal axis (HPA. Therefore, we found it interesting to study polymorphisms of genes involved in the HPA axis (CRHR1, NR3C1, and AVPBR1. The study was performed on 597 patients, 225 of whom had a history of suicide attempts. We did not observe any significant differences in the studied polymorphisms between the group of patients with a history of suicide attempts and the control subjects. Our haplotype analysis of the AVPR1b gene revealed an association between the GCA haplotype and suicide attempts; however, this association was not significant after correcting for multiple testing. We did not observe any other association in haplotype and MDR analysis. We report here a comprehensive analysis of the HPA axis genes and a lack of association for genetic variations regarding the risk of suicide attempts in affective disorder patients. Nonetheless, the inconsistencies with the previously published results indicate the importance of the further investigation of these polymorphisms with respect to the risk of suicide attempts.

  11. The Effect of Nicotine on HPA Axis Activity in Females is Modulated by the FKBP5 Genotype.

    Science.gov (United States)

    Koopmann, Anne; Bez, Jennifer; Lemenager, Tagrid; Hermann, Derik; Dinter, Christina; Reinhard, Iris; Schuster, Rilana; Wiedemann, Klaus; Winterer, Georg; Kiefer, Falk

    2016-05-01

    Tobacco smoking modulates activity in the hypothalamic-pituitary-adrenal (HPA) axis and is used to cope with stress, especially by females. The single nucleotide polymorphism (SNP) rs1360780, linked to FK506-binding protein 51 (FKBP5), has been shown to affect HPA axis functioning, and has thus been suggested as a promising candidate for indicating vulnerability to stress-related disorders. The aim of this study was to investigate the interaction between nicotine consumption and rs1360780 on cortisol plasma levels in females. A total of 296 female smokers (assessed by the Fagerström Test for Nicotine Dependence; FTND) were genotyped for the SNP rs1360780. We measured participants' cortisol plasma concentration in blood plasma collected 3 h after standardized tobacco smoking exposure. In the 36 TT-homozygotes, we found a significant negative correlation between the FTND sum score and cortisol plasma concentrations. Using linear regression analysis, we found that the FTND sum score accounted for 12.4% of the variance of cortisol plasma levels. This association was not detected in C-allele carriers. Our results suggest that nicotine is an important confounder in the modulation of HPA axis activity by FKBP5. In light of these findings, future studies on FKBP5 should seek to include data on nicotine consumption as a covariate.

  12. Conditioned taste aversion: modulation by 5-HT receptor activity and corticosterone

    DEFF Research Database (Denmark)

    Boris, Gorzalka; Hanson, Laura; Harrington, J

    2003-01-01

    Two experiments were designed to elucidate the involvement of the hypothalamic-pituitary-adrenal axis and the 5-hydroxytryptamine (5-HT) system in the acquisition of lithium chloride-conditioned taste aversion. In Experiment 1, rats were administered either vehicle or 50 mg/kg nefazodone daily fo......, corticosterone-treated animals required more trials to reach extinction. These results suggest the involvement of both the 5-HT system and the hypothalamic-pituitary-adrenal axis in lithium chloride-conditioned taste aversion....

  13. Self-Knowledge Dim-Out: Stress Impairs Metacognitive Accuracy.

    Science.gov (United States)

    Reyes, Gabriel; Silva, Jaime R; Jaramillo, Karina; Rehbein, Lucio; Sackur, Jérôme

    2015-01-01

    Modulation of frontal lobes activity is believed to be an important pathway trough which the hypothalamic-pituitary-adrenal (HPA) axis stress response impacts cognitive and emotional functioning. Here, we investigate the effects of stress on metacognition, which is the ability to monitor and control one's own cognition. As the frontal lobes have been shown to play a critical role in metacognition, we predicted that under activation of the HPA axis, participants should be less accurate in the assessment of their own performances in a perceptual decision task, irrespective of the effect of stress on the first order perceptual decision itself. To test this prediction, we constituted three groups of high, medium and low stress responders based on cortisol concentration in saliva in response to a standardized psycho-social stress challenge (the Trier Social Stress Test). We then assessed the accuracy of participants' confidence judgments in a visual discrimination task. As predicted, we found that high biological reactivity to stress correlates with lower sensitivity in metacognition. In sum, participants under stress know less when they know and when they do not know.

  14. Self-Knowledge Dim-Out: Stress Impairs Metacognitive Accuracy

    Science.gov (United States)

    Reyes, Gabriel; Silva, Jaime R.; Jaramillo, Karina; Rehbein, Lucio; Sackur, Jérôme

    2015-01-01

    Modulation of frontal lobes activity is believed to be an important pathway trough which the hypothalamic-pituitary-adrenal (HPA) axis stress response impacts cognitive and emotional functioning. Here, we investigate the effects of stress on metacognition, which is the ability to monitor and control one's own cognition. As the frontal lobes have been shown to play a critical role in metacognition, we predicted that under activation of the HPA axis, participants should be less accurate in the assessment of their own performances in a perceptual decision task, irrespective of the effect of stress on the first order perceptual decision itself. To test this prediction, we constituted three groups of high, medium and low stress responders based on cortisol concentration in saliva in response to a standardized psycho-social stress challenge (the Trier Social Stress Test). We then assessed the accuracy of participants' confidence judgments in a visual discrimination task. As predicted, we found that high biological reactivity to stress correlates with lower sensitivity in metacognition. In sum, participants under stress know less when they know and when they do not know. PMID:26252222

  15. Interactions of chronic lead exposure and intermittent stress: consequences for brain catecholamine systems and associated behaviors and HPA axis function.

    Science.gov (United States)

    Virgolini, Miriam B; Chen, Kevin; Weston, Doug D; Bauter, Mark R; Cory-Slechta, Deborah A

    2005-10-01

    Elevated lead (Pb) burden and high stress levels are co-occurring risk factors in low socioeconomic status (SES) children. Our previous work demonstrated that maternal Pb exposure can permanently alter hypothalamic-pituitary-adrenal (HPA) axis function and responsivity to stress challenges in offspring. The current study sought to determine the consequences of chronic Pb exposures initiated later in development combined with variable intermittent stress challenges. Male rats were exposed chronically from weaning to 0, 50, or 150 ppm Pb acetate drinking solutions (producing blood Pb levels of challenges including novelty, cold, and restraint, was measured as changes in Fixed Interval (FI) schedule-controlled behavior in a subset of rats within each group. FI performance was modified by novelty stress only in Pb-treated rats, whereas cold and restraint stress effects were comparable across groups. Novelty elevated corticosterone equivalently across groups, but cold stress markedly increased corticosterone only in Pb-treated groups. The pattern of Pb-induced changes in serotonin (5-HT) or its metabolite 5-HIAA in frontal cortex, nucleus accumbens, striatum, and hypothalamus resembled that observed for basal corticosterone levels indicating a relationship between these variables. In addition to suggesting the potential for HPA axis-mediated effects of Pb on the central nervous system, these findings also raise questions about whether single chemicals studied in isolation from other relevant risk factors can adequately identify neurotoxic hazards.

  16. Maternal depression across the first years of life compromises child psychosocial adjustment; relations to child HPA-axis functioning.

    Science.gov (United States)

    Apter-Levi, Yael; Pratt, Maayan; Vakart, Adam; Feldman, Michal; Zagoory-Sharon, Orna; Feldman, Ruth

    2016-02-01

    Maternal depression across the first years of life negatively impacts children's development. One pathway of vulnerability may involve functioning of the hypothalamic-pituitary-adrenal (HPA) axis. We utilize a community cohort of 1983 women with no comorbid risk repeatedly assessed for depression from birth to six years to form two groups; chronically depressed (N=40) and non-depressed (N=91) women. At six years, mother and child underwent psychiatric diagnosis, child salivary cortisol (CT) was assessed three times during a home-visit, mother-child interaction was videotaped, and child empathy was coded from behavioral paradigms. Latent Growth curve Model using Structural Equation Modeling (SEM) estimated the links between maternal depression and mother's negative parenting and three child outcomes; psychopathology, social withdrawal, and empathy as related to child CT baseline and variability. Depressed mothers displayed more negative parenting and their children showed more Axis-I psychopathology and social withdrawal. SEM analysis revealed that maternal depression was associated with reduced CT variability, which predicted higher child psychopathology and social withdrawal. Whereas all children exhibited similar initial levels of CT, children of controls reduced CT levels over time while children of depressed mothers maintained high, non-flexible levels. Mother negativity was related to lower initial CT levels, which predicted decreased empathy. Findings suggest that chronic maternal depression may compromise children's social-emotional adjustment by diminishing HPA-system flexibility as well as limiting the mother's capacity to provide attuned and predictable caregiving.

  17. Lack of specific association between panicogenic properties of caffeine and HPA-axis activation. A placebo-controlled study of caffeine challenge in patients with panic disorder.

    Science.gov (United States)

    Masdrakis, Vasilios G; Markianos, Manolis; Oulis, Panagiotis

    2015-09-30

    A subgroup of patients with Panic Disorder (PD) exhibits increased sensitivity to caffeine administration. However, the association between caffeine-induced panic attacks and post-caffeine hypothalamic-pituitary-adrenal (HPA)-axis activation in PD patients remains unclear. In a randomized, double-blind, cross-over experiment, 19 PD patients underwent a 400-mg caffeine-challenge and a placebo-challenge, both administered in the form of instant coffee. Plasma levels of adrenocorticotropic hormone (ACTH), cortisol and dehydroepiandrosterone sulfate (DHEAS) were assessed at both baseline and post-challenge. No patient panicked after placebo-challenge, while nine patients (47.3%) panicked after caffeine-challenge. Placebo administration did not result in any significant change in hormones' plasma levels. Overall, sample's patients demonstrated significant increases in ACTH, cortisol, and DHEAS plasma levels after caffeine administration. However, post-caffeine panickers and non-panickers did not differ with respect to the magnitude of the increases. Our results indicate that in PD patients, caffeine-induced panic attacks are not specifically associated with HPA-axis activation, as this is reflected in post-caffeine increases in ACTH, cortisol and DHEAS plasma levels, suggesting that caffeine-induced panic attacks in PD patients are not specifically mediated by the biological processes underlying fear or stress. More generally, our results add to the evidence that HPA-axis activation is not a specific characteristic of panic.

  18. Identification and characterization of HPA-axis reactivity endophenotypes in a cohort of female PTSD patients.

    Science.gov (United States)

    Zaba, Monika; Kirmeier, Thomas; Ionescu, Irina A; Wollweber, Bastian; Buell, Dominik R; Gall-Kleebach, Dominique J; Schubert, Christine F; Novak, Bozidar; Huber, Christine; Köhler, Katharina; Holsboer, Florian; Pütz, Benno; Müller-Myhsok, Bertram; Höhne, Nina; Uhr, Manfred; Ising, Marcus; Herrmann, Leonie; Schmidt, Ulrike

    2015-05-01

    Analysis of the function of the hypothalamic-pituitary-adrenal (HPA)-axis in patients suffering from posttraumatic stress disorder (PTSD) has hitherto produced inconsistent findings, inter alia in the Trier Social Stress Test (TSST). To address these inconsistencies, we compared a sample of 23 female PTSD patients with either early life trauma (ELT) or adult trauma (AT) or combined ELT and AT to 18 age-matched non-traumatized female healthy controls in the TSST which was preceded by intensive baseline assessments. During the TSST, we determined a variety of clinical, psychological, endocrine and cardiovascular parameters as well as expression levels of four HPA-axis related genes. Using a previously reported definition of HPA-axis responsive versus non-responsive phenotypes, we identified for the first time two clinically and biologically distinct HPA-axis reactivity subgroups of PTSD. One subgroup ("non-responders") showed a blunted HPA-axis response and distinct clinical and biological characteristics such as a higher prevalence of trauma-related dissociative symptoms and of combined AT and ELT as well as alterations in the expression kinetics of the genes encoding for the mineralocorticoid receptor (MR) and for FK506 binding protein 51 (FKBP51). Interestingly, this non-responder subgroup largely drove the relatively diminished HPA axis response of the total cohort of PTSD patients. These findings are limited by the facts that the majority of patients was medicated, by the lack of traumatized controls and by the relatively small sample size. The here for the first time identified and characterized HPA-axis reactivity endophenotypes offer an explanation for the inconsistent reports on HPA-axis function in PTSD and, moreover, suggest that most likely other factors than HPA-axis reactivity play a decisive role in determination of PTSD core symptom severity.

  19. HPA axis dysregulation in men with hypersexual disorder.

    Science.gov (United States)

    Chatzittofis, Andreas; Arver, Stefan; Öberg, Katarina; Hallberg, Jonas; Nordström, Peter; Jokinen, Jussi

    2016-01-01

    Hypersexual disorder integrating pathophysiological aspects such as sexual desire deregulation, sexual addiction, impulsivity and compulsivity was suggested as a diagnosis for the DSM-5. However, little is known about the neurobiology behind this disorder. A dysregulation of the hypothalamic pituitary adrenal (HPA) axis has been shown in psychiatric disorders but has not been investigated in hypersexual disorder. The aim of this study was to investigate the function of the HPA axis in hypersexual disorder. The study includes 67 male patients with hypersexual disorder and 39 healthy male volunteers. Basal morning plasma levels of cortisol and ACTH were assessed and low dose (0.5mg) dexamethasone suppression test was performed with cortisol and ACTH measured post dexamethasone administration. Non-suppression status was defined with DST-cortisol levels ≥ 138 nmol/l. The Sexual Compulsive scale (SCS), Hypersexual disorder current assessment scale (HD:CAS), Montgomery-Åsberg Depression Scale-self rating (MADRS-S) and Childhood trauma questionnaire (CTQ), were used for assessing hypersexual behavior, depression severity and early life adversity. Patients with hypersexual disorder were significantly more often DST non-suppressors and had significantly higher DST-ACTH levels compared to healthy volunteers. The patients reported significantly more childhood trauma and depression symptoms compared to healthy volunteers. CTQ scores showed a significant negative correlation with DST-ACTH whereas SCS and HD:CAS scores showed a negative correlation with baseline cortisol in patients. The diagnosis of hypersexual disorder was significantly associated DST non-suppression and higher plasma DST-ACTH even when adjusted for childhood trauma. The results suggest HPA axis dysregulation in male patients with hypersexual disorder.

  20. [THE INFLUENCE OF MELANIN ON THE GASTRIC MUCOSA AND HYPOTHALAMIC-PITUITARY-ADRENOCORTICAL AXIS UNDER ACUTE STRESS CONDITIONS].

    Science.gov (United States)

    Golyshkin, D V; Falalyeyeva, T M; Neporada, K S; Beregova, T V

    2015-01-01

    We studied the influence of melanin from yeast-like fungi Nadsoniella nigra strain X1 on the changes of the levels of adrenocorticotropic hormone (ACTH) and cortisol in blood serum of rats, adrenal glands weight ratio and lesions of the gastric mucosa (GM) caused by neuromuscular tension by Selye. Melanin administration restored functioning of the hypothalamic-pituitary-adrenal axis that was evident by an increase of ACTH concentration by 42% and a decrease of cortisol concentration by 19% compared to the rats injected with water (group 2). In rats treated with melanin, the adrenal glands weight ratio, didn't differ from intact control group of the rats. Melanin decreased ulcers area by 64% and reduced the content of free hydroxyproline by 29%, the free fucose by 16% and the free hexuronic acids by 24% in the GM compared to the group 2 of the rats. It is established that the mechanism of melanin stress-protective properties are based on its regulation of the glucocorticoids secretion and prevention of GM collagen and extracellular matrix substances depolymerization. Melanin possesses gastroprotective properties and is a perspective agent for preventing and treatment of consequences of the stress influence on the organism.

  1. Temporomandibular disorders and declarative memory.

    Science.gov (United States)

    Yang, Dongmei; Ye, Ling

    2011-05-01

    Temporomandibular disorder (TMD) is a somatic manifestation of stress. Previous researches suggested hypothalamic-pituitary-adrenal (HPA) axis hyperactivity in TMD, through which TMD patients exhibited abnormalities of the stress response hormone - causing additional cortisol release. Increased cortisol, the principal circulating glucocorticoid in humans, would impair memory retrieval of declarative material. This effect on memory retrieval may in particular be due to glucocorticoid receptors (GR) in the hippocampus. The hypothesis we proposed is that TMD might result in declarative memory impairment by increasing the cortisol.

  2. Blubber transcriptome response to acute stress axis activation involves transient changes in adipogenesis and lipolysis in a fasting-adapted marine mammal

    Science.gov (United States)

    Khudyakov, J. I.; Champagne, C. D.; Meneghetti, L. M.; Crocker, D. E.

    2017-01-01

    Stress can compromise an animal’s ability to conserve metabolic stores and participate in energy-demanding activities that are critical for fitness. Understanding how wild animals, especially those already experiencing physiological extremes (e.g. fasting), regulate stress responses is critical for evaluating the impacts of anthropogenic disturbance on physiology and fitness, key challenges for conservation. However, studies of stress in wildlife are often limited to baseline endocrine measurements and few have investigated stress effects in fasting-adapted species. We examined downstream molecular consequences of hypothalamic-pituitary-adrenal (HPA) axis activation by exogenous adrenocorticotropic hormone (ACTH) in blubber of northern elephant seals due to the ease of blubber sampling and its key role in metabolic regulation in marine mammals. We report the first phocid blubber transcriptome produced by RNAseq, containing over 140,000 annotated transcripts, including metabolic and adipocytokine genes of interest. The acute response of blubber to stress axis activation, measured 2 hours after ACTH administration, involved highly specific, transient (lasting <24 hours) induction of gene networks that promote lipolysis and adipogenesis in mammalian adipocytes. Differentially expressed genes included key adipogenesis factors which can be used as blubber-specific markers of acute stress in marine mammals of concern for which sampling of other tissues is not possible. PMID:28186107

  3. Interaction of basal forebrain cholinergic neurons with the glucocorticoid system in stress regulation and cognitive impairment.

    Science.gov (United States)

    Paul, Saswati; Jeon, Won Kyung; Bizon, Jennifer L; Han, Jung-Soo

    2015-01-01

    A substantial number of studies on basal forebrain (BF) cholinergic neurons (BFCN) have provided compelling evidence for their role in the etiology of stress, cognitive aging, Alzheimer's disease (AD), and other neurodegenerative diseases. BFCN project to a broad range of cortical sites and limbic structures, including the hippocampus, and are involved in stress and cognition. In particular, the hippocampus, the primary target tissue of the glucocorticoid stress hormones, is associated with cognitive function in tandem with hypothalamic-pituitary-adrenal (HPA) axis modulation. The present review summarizes glucocorticoid and HPA axis research to date in an effort to establish the manner in which stress affects the release of acetylcholine (ACh), glucocorticoids, and their receptor in the context of cognitive processes. We attempt to provide the molecular interactive link between the glucocorticoids and cholinergic system that contributes to BFCN degeneration in stress-induced acceleration of cognitive decline in aging and AD. We also discuss the importance of animal models in facilitating such studies for pharmacological use, to which could help decipher disease states and propose leads for pharmacological intervention.

  4. Interaction of basal forebrain cholinergic neurons with the glucocorticoid system in stress regulation and cognitive impairment

    Directory of Open Access Journals (Sweden)

    Saswati ePaul

    2015-04-01

    Full Text Available A substantial number of studies on basal forebrain cholinergic neurons (BFCN have provided compelling evidence for their role in the etiology of stress, cognitive aging, Alzheimer’s disease (AD, and other neurodegenerative diseases. BFCN project to a broad range of cortical sites and limbic structures, including the hippocampus, and are involved in stress and cognition. In particular, the hippocampus, the primary target tissue of the glucocorticoid stress hormones, is associated with cognitive function in tandem with hypothalamic-pituitary-adrenal (HPA axis modulation. The present review summarizes glucocorticoid and HPA axis research to date in an effort to establish the manner in which stress affects the release of acetylcholine, glucocorticoids, and their receptor in the context of cognitive processes. We attempt to provide the molecular interactive link between the glucocorticoids and cholinergic system that contributes to BFCN degeneration in stress-induced acceleration of cognitive decline in aging and AD. We also discuss the importance of animal models in facilitating such studies for pharmacological use, which could help decipher disease states and propose leads for pharmacological intervention.

  5. HPA Axis in Major Depression: Cortisol, Clinical Symptomatology, and Genetic Variation Predict Cognition

    Science.gov (United States)

    Keller, Jennifer; Gomez, Rowena; Williams, Gordon; Lembke, Anna; Lazzeroni, Laura; Murphy, Greer M.; Schatzberg, Alan F.

    2016-01-01

    The Hypothalamic Pituitary Adrenal (HPA) axis has been implicated in the pathophysiology of a variety of mood and cognitive disorders. Neuroendocrine studies have demonstrated HPA axis overactivity in major depression, a relationship of HPA axis activity to cognitive performance, and a potential role of HPA axis genetic variation in cognition. The present study investigated the simultaneous roles HPA axis activity, clinical symptomatology, and HPA genetic variation play in cognitive performance. Patients with major depression with psychosis (PMD) and without psychosis (NPMD) and healthy controls (HC) were studied. All participants underwent a diagnostic interview and psychiatric ratings, a comprehensive neuropsychological battery, overnight hourly blood sampling for cortisol, and genetic assessment. Cognitive performance differed as a function of depression subtype. Across all subjects, cognitive performance was negatively correlated with higher cortisol, and PMD patients had higher cortisol than did NPMDs and HCs. Cortisol, clinical symptoms, and variation in genes, NR3C1 (glucocorticoid receptor - GR) and NR3C2 (minercorticoid receptor – MR) that encode for glucocorticoid and mineralcorticoid receptors, predicted cognitive performance. Beyond the effects of cortisol, demographics, and clinical symptoms, NR3C1 variation predicted attention and working memory, whereas NR3C2 polymorphisms predicted memory performance. These findings parallel the distribution of GR and MR in primate brain and their putative roles in specific cognitive tasks. HPA axis genetic variation and activity were important predictors of cognition across the entire sample of depressed subjects and healthy controls. GR and MR genetic variation predicted unique cognitive functions, beyond the influence of cortisol and clinical symptoms. GR genetic variation was implicated in attention and working memory, whereas MR was implicated in verbal memory. PMID:27528460

  6. HPA axis in major depression: cortisol, clinical symptomatology and genetic variation predict cognition.

    Science.gov (United States)

    Keller, J; Gomez, R; Williams, G; Lembke, A; Lazzeroni, L; Murphy, G M; Schatzberg, A F

    2016-08-16

    The hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the pathophysiology of a variety of mood and cognitive disorders. Neuroendocrine studies have demonstrated HPA axis overactivity in major depression, a relationship of HPA axis activity to cognitive performance and a potential role of HPA axis genetic variation in cognition. The present study investigated the simultaneous roles HPA axis activity, clinical symptomatology and HPA genetic variation play in cognitive performance. Patients with major depression with psychotic major depression (PMD) and with nonpsychotic major depression (NPMD) and healthy controls (HC) were studied. All participants underwent a diagnostic interview and psychiatric ratings, a comprehensive neuropsychological battery, overnight hourly blood sampling for cortisol and genetic assessment. Cognitive performance differed as a function of depression subtype. Across all subjects, cognitive performance was negatively correlated with higher cortisol, and PMD patients had higher cortisol than did NPMDs and HCs. Cortisol, clinical symptoms and variation in genes, NR3C1 (glucocorticoid receptor; GR) and NR3C2 (mineralocorticoid receptor; MR) that encode for GRs and MRs, predicted cognitive performance. Beyond the effects of cortisol, demographics and clinical symptoms, NR3C1 variation predicted attention and working memory, whereas NR3C2 polymorphisms predicted memory performance. These findings parallel the distribution of GR and MR in primate brain and their putative roles in specific cognitive tasks. HPA axis genetic variation and activity were important predictors of cognition across the entire sample of depressed subjects and HR. GR and MR genetic variation predicted unique cognitive functions, beyond the influence of cortisol and clinical symptoms. GR genetic variation was implicated in attention and working memory, whereas MR was implicated in verbal memory.Molecular Psychiatry advance online publication, 16 August 2016; doi

  7. Brain development and cognitive, psychosocial, and psychiatric functioning in classical 21-hydroxylase deficiency.

    Science.gov (United States)

    Meyer-Bahlburg, Heino F L

    2011-01-01

    The disturbance of the hypothalamic-pituitary- adrenal axis characteristic of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is likely to affect brain development, yet neuroanatomic work is only beginning. Fetal hyperandrogenemia in 46, XX 21-OHD leads to masculinized brain organization and, consequently, at later stages of development, to masculinized gender-related behavior and cognitive function, including, although relatively uncommonly, gender identity. Genital masculinization as well as its surgical treatment has implications for social stigmatization and sexual functioning. CAH-associated electrolyte crises in infancy and later may result in severe cognitive impairment. Psychiatric disorders are somewhat increased, especially in patients with severe degrees of CAH.

  8. Antidepressant-like activity of resveratrol treatment in the forced swim test and tail suspension test in mice: the HPA axis, BDNF expression and phosphorylation of ERK.

    Science.gov (United States)

    Wang, Zhen; Gu, Jianhua; Wang, Xueer; Xie, Kai; Luan, Qinsong; Wan, Nianqing; Zhang, Qun; Jiang, Hong; Liu, Dexiang

    2013-11-01

    Resveratrol is a natural polyphenol enriched in Polygonum cuspidatum and has diverse biological activities. There is only limited information about the antidepressant-like effect of resveratrol. The present study assessed whether resveratrol treatment (20, 40 and 80mg/kg, i.p., 21days) has an antidepressant-like effect on the forced swim test (FST) and tail suspension test (TST) in mice and examined what its molecular targets might be. The results showed that resveratrol administration produced antidepressant-like effects in mice, evidenced by the reduced immobility time in the FST and TST, while it had no effect on the locomotor activity in the open field test. Resveratrol treatment significantly reduced serum corticosterone levels, which had been elevated by the FST and TST. Moreover, resveratrol increased brain-derived neurotrophic factor (BDNF) protein and extracellular signal-regulated kinase (ERK) phosphorylation levels in the prefrontal cortex and hippocampus. All of these antidepressant-like effects of resveratrol were essentially similar to those observed with the clinical antidepressant, fluoxetine. These results suggest that the antidepressant-like effects of resveratrol in the FST and TST are mediated, at least in part, by modulating hypothalamic-pituitary-adrenal axis, BDNF and ERK phosphorylation expression in the brain region of mice.

  9. Hyper- and hypocortisolism in bipolar disorder - A beneficial influence of lithium on the HPA-axis?

    Science.gov (United States)

    Maripuu, Martin; Wikgren, Mikael; Karling, Pontus; Adolfsson, Rolf; Norrback, Karl-Fredrik

    2017-04-15

    A hyperactive hypothalamic-pituitary-adrenal axis (HPA-axis) is a well-known phenomenon in bipolar disorder (BD). However, hypocortisolism has also been described and found associated with depression, low quality of life and cardiovascular risk factors in BD patients. Although the pathophysiology related to hypocortisolism in BD is largely unknown, hypocortisolism is associated with chronic stress exposure and after inducing an initial rise in cortisol long-term stress may result in a transition to hypocortisolism. BD patients are throughout life often exposed to chronic stress. We therefore hypothesized that higher age would be associated with lower HPA-axis activity especially among patients without previous mood stabilizing treatment. This cross-sectional study consisted of 159 bipolar outpatients and 258 controls. A low-dose-dexamethasone-suppression-test (DST) was used to measure HPA-axis activity. Patients with BD showed a negative association between post DST cortisol and age (-3.0 nmol/l per year; p=0.007). This association gradually increased in subgroups that were naïve to lithium (-7.7 nmol/l per year; p=0.001) and "all mood stabilizers" (-11.4 nmol/l per year; p=0.004). Patients exhibiting hypercortisolism were characterized by younger age and female gender, whereas patients exhibiting hypocortisolism were characterized by long disease duration without prophylactic lithium treatment as well as absence of current lithium medication. Cross sectional study design. There was a negative association between HPA-axis activity and age in BD, rendering BD patients at risk for developing hypocortisolism. This association was most pronounced among patients without previous or current lithium prophylaxis. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Chronic activation of NPFFR2 stimulates the stress-related depressive behaviors through HPA axis modulation.

    Science.gov (United States)

    Lin, Ya-Tin; Liu, Tzu-Yu; Yang, Ching-Yao; Yu, Yu-Lian; Chen, Ting-Chun; Day, Yuan-Ji; Chang, Che-Chien; Huang, Guo-Jen; Chen, Jin-Chung

    2016-09-01

    Neuropeptide FF (NPFF) is a morphine-modulating peptide that regulates the analgesic effect of opioids, and also controls food consumption and cardiovascular function through its interaction with two cognate receptors, NPFFR1 and NPFFR2. In the present study, we explore a novel modulatory role for NPFF-NPFFR2 in stress-related depressive behaviors. In a mouse model of chronic mild stress (CMS)-induced depression, the expression of NPFF significantly increased in the hypothalamus, hippocampus, medial prefrontal cortex (mPFC) and amygdala. In addition, transgenic (Tg) mice over-expressing NPFFR2 displayed clear depression and anxiety-like behaviors with hyperactivity in the hypothalamic-pituitary-adrenal (HPA) axis, reduced expression of glucocorticoid receptor (GR) and neurogenesis in the hippocampus. Furthermore, acute treatment of NPFFR2 agonists in wild-type (WT) mice enhanced the activity of the HPA axis, and chronic administration resulted in depressive and anxiety-like behaviors. Chronic stimulation of NPFFR2 also decreased the expression of hippocampal GR and led to persistent activation of the HPA axis. Strikingly, bilateral intra-paraventricular nucleus (PVN) injection of NPFFR2 shRNA predominately inhibits the depressive-like behavior in CMS-exposed mice. Antidepressants, fluoxetine and ketamine, effectively relieved the depressive behaviors of NPFFR2-Tg mice. We speculate that persistent NPFFR2 activation, in particular in the hypothalamus, up-regulates the HPA axis and results in long-lasting increases in circulating corticosterone (CORT), consequently damaging hippocampal function. This novel role of NPFFR2 in regulating the HPA axis and hippocampal function provides a new avenue for combating depression and anxiety-like disorder.

  11. Suppression of the HPA Axis During Cholestasis Can Be Attributed to Hypothalamic Bile Acid Signaling.

    Science.gov (United States)

    McMillin, Matthew; Frampton, Gabriel; Quinn, Matthew; Divan, Ali; Grant, Stephanie; Patel, Nisha; Newell-Rogers, Karen; DeMorrow, Sharon

    2015-12-01

    Suppression of the hypothalamic-pituitary-adrenal (HPA) axis has been shown to occur during cholestatic liver injury. Furthermore, we have demonstrated that in a model of cholestasis, serum bile acids gain entry into the brain via a leaky blood brain barrier and that hypothalamic bile acid content is increased. Therefore, the aim of the current study was to determine the effects of bile acid signaling on the HPA axis. The data presented show that HPA axis suppression during cholestatic liver injury, specifically circulating corticosterone levels and hypothalamic corticotropin releasing hormone (CRH) expression, can be attenuated by administration of the bile acid sequestrant cholestyramine. Secondly, treatment of hypothalamic neurons with various bile acids suppressed CRH expression and secretion in vitro. However, in vivo HPA axis suppression was only evident after the central injection of the bile acids taurocholic acid or glycochenodeoxycholic acid but not the other bile acids studied. Furthermore, we demonstrate that taurocholic acid and glycochenodeoxycholic acid are exerting their effects on hypothalamic CRH expression after their uptake through the apical sodium-dependent bile acid transporter and subsequent activation of the glucocorticoid receptor. Taken together with previous studies, our data support the hypothesis that during cholestatic liver injury, bile acids gain entry into the brain, are transported into neurons through the apical sodium-dependent bile acid transporter and can activate the glucocorticoid receptor to suppress the HPA axis. These data also lend themselves to the broader hypothesis that bile acids may act as central modulators of hypothalamic peptides that may be altered during liver disease.

  12. 3xTg-AD Mice Exhibit an Activated Central Stress Axis during Early-Stage Pathology

    Science.gov (United States)

    Hebda-Bauer, Elaine K.; Simmons, Tracy A.; Sugg, Andrew; Ural, Eren; Stewart, James A.; Beals, James L.; Wei, Qiang; Watson, Stanley J.; Akil, Huda

    2012-01-01

    Activation of the hypothalamic-pituitary-adrenal (HPA) axis occurs in response to the organism’s innate need for homeostasis. The glucocorticoids (GCs) that are released into the circulation upon acute activation of the HPA axis perform stress-adaptive functions and provide negative feedback to turn off the HPA axis, but can be detrimental when in excess. Long-term activation of the HPA axis (such as with chronic stress) enhances susceptibility to neuronal dysfunction and death, and increases vulnerability to Alzheimer’s disease (AD). However, little is known how components of the HPA axis, upstream of GCs, impact vulnerability to AD. This study examined basal gene expression of stress-related molecules in brains of 3xTg-AD mice during early-stage pathology. Basal glucocorticoid levels and mRNA expression of the glucocorticoid receptor (GR), mineralocorticoid receptor (MR), and corticotropic releasing hormone (CRH) in several stress- and emotionality-related brain regions were measured in 3–4-month-old 3xTg-AD mice. Despite normal glucocorticoid levels, young 3xTg-AD mice exhibit an activated central HPA axis, with altered mRNA levels of MR and GR in the hippocampus, GR and CRH in the paraventricular nucleus of the hypothalamus, GR and CRH in the central nucleus of the amygdala, and CRH in the bed nucleus of the stria terminalis. This HPA axis activation is present during early-stage neuropathology when 3xTg-AD mice show mild behavioral changes, suggesting an ongoing neuroendocrine regulation that precedes the onset of severe AD-like pathology and behavioral deficits. PMID:22976078

  13. Associations between early life experience, chronic HPA axis activity, and adult social rank in rhesus monkeys.

    Science.gov (United States)

    Dettmer, Amanda M; Wooddell, Lauren J; Rosenberg, Kendra L; Kaburu, Stefano S K; Novak, Melinda A; Meyer, Jerrold S; Suomi, Stephen J

    2017-02-01

    Early life experience and socioeconomic status (SES) are well-established predictors of health outcomes in people. Both factors likely influence health outcomes via hypothalamic-pituitary-adrenal (HPA) axis regulation. However, it is unclear how early experience and HPA axis activity influence adult social status. We studied differentially reared female rhesus monkeys (Macaca mulatta, N = 90) as models to test the hypothesis that chronic HPA axis activity assessed via hair cortisol concentrations (HCCs) mediated the relationship between early life experience and adult social rank. We found that mother-peer-reared (MPR) monkeys acquired higher social ranks than either of the two nursery-reared (NR) groups (peer-reared, PR, or surrogate-peer-reared, SPR monkeys) (β = -0.07, t(89) = -2.16, p = 0.034). We also found that MPR HCCs were lower during the juvenile period at 18 months (F(2,25) = 3.49, p = 0.047). Furthermore, for MPR but not NR monkeys, changes in HCCs from 18 to 24 months (r(s) = -0.627, p = 0.039) and adult HCCs (r(s) = -0.321, p = 0.03) were negatively correlated with adult social rank. These findings suggest that chronic HPA axis regulation in juvenility, and perhaps in adulthood, may influence adult social status for primates that experience typical early rearing. However, early life adversity may result in dissociation between neuroendocrine stress regulation and adult social competence, which may be risk factors for adverse health outcomes.

  14. Effects of childhood trauma on HPA-axis reactivity in women free of lifetime psychopathology.

    Science.gov (United States)

    Klaassens, Ellen R; van Noorden, Martijn S; Giltay, Erik J; van Pelt, Johannes; van Veen, Tineke; Zitman, Frans G

    2009-08-01

    Exposure to childhood trauma may induce persistent changes in Hypothalamic-Pituitary-Adrenal (HPA)-axis functioning even in the absence of current psychopathology. Because previous studies did not systematically exclude subjects with lifetime psychiatric morbidity, prevalent psychopathology may have confounded the association. In this study we investigated whether women exposed to childhood trauma, but without a history of psychiatric disorders, show alterations in HPA-axis functioning. We included 10 women exposed to significant childhood trauma and 12 non-exposed women. All women were between 29 and 64 years old,mentally and physically healthy, and without current or lifetime psychopathology. HPA-axis functioning was assessed as 1) basal activity with salivary cortisol patterns over 8 time points on two consecutive sampling days and 2) plasma cortisol and adrenocorticotropic hormone (ACTH) reactivity over 7 time points after the combined dexamethasone/corticotropin-releasing hormone (dex/CRH) challenge test. Basal salivary cortisol output did not differ between trauma-exposed compared to non-exposed women. Significantly blunted plasma cortisol and ACTH responses in response to dex/CRH administration were found in the trauma exposed compared to the non-exposed women (F(1,20)=5.08, p=0.04 and F(1,20)=5.23, p=0.03 respectively). Adjusting for age, body mass index (BMI), oral contraceptive use, and menopausal status,somewhat weakened the associations for cortisol as well as ACTH (F(1,16)=3.30, p=0.09) and F(1,16)=2.17, p=0.16 respectively), but for cortisol absolute differences in point estimates were largely unaffected.Although basal cortisol patterns were similar in the two groups, exposure to childhood trauma seemed to be related to a blunted HPA-axis reactivity in women who were free of current or lifetime psychopathology.

  15. Alterations in HPA-axis and autonomic nervous system functioning in childhood anxiety disorders point to a chronic stress hypothesis.

    Science.gov (United States)

    Dieleman, Gwendolyn C; Huizink, Anja C; Tulen, Joke H M; Utens, Elisabeth M W J; Creemers, Hanneke E; van der Ende, Jan; Verhulst, Frank C

    2015-01-01

    It is of debate whether or not childhood anxiety disorders (AD) can be captured by one taxonomic construct. This study examined whether perceived arousal (PA), autonomic nervous system (ANS) and hypothalamic-pituitary-adrenal (HPA) axis measures can distinguish children with different primary diagnoses of clinical anxiety disorders (AD) from each other, and from a general population reference group (GP). The study sample consisted of 152 AD children (comparing separation anxiety disorder, generalized anxiety disorder, social phobia and specific phobia), aged 8- to 12-years, and 200 same-aged reference children. HPA-axis functioning was measured by a diurnal cortisol profile. ANS functioning was measured by continuous measures of skin conductance level in rest and during a mental arithmetic task and high frequency heart rate variability in rest. PA was assessed by a questionnaire. The AD sample showed lower high frequency heart rate variability during rest, heightened anticipatory PA, higher basal and reactive skin conductance levels and lower basal HPA-axis functioning compared to the GP sample. The existence of three or more clinical disorders, i.e. a high clinical 'load', was associated with lower basal HPA-axis functioning, higher skin conductance level and lower posttest PA. Specific phobia could be discerned from social phobia and separation anxiety disorder on higher skin conductance level. Our findings indicated that children with AD have specific psychophysiological characteristics, which resemble the psychophysiological characteristics of chronic stress. A high clinical 'load' is associated with an altered ANS and HPA-axis functioning. Overall, ANS and HPA-axis functioning relate to AD in general, accept for specific phobia. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. HPA AXIS RELATED GENES AND RESPONSE TO PSYCHOLOGICAL THERAPIES: GENETICS AND EPIGENETICS.

    Science.gov (United States)

    Roberts, Susanna; Keers, Robert; Lester, Kathryn J; Coleman, Jonathan R I; Breen, Gerome; Arendt, Kristian; Blatter-Meunier, Judith; Cooper, Peter; Creswell, Cathy; Fjermestad, Krister; Havik, Odd E; Herren, Chantal; Hogendoorn, Sanne M; Hudson, Jennifer L; Krause, Karen; Lyneham, Heidi J; Morris, Talia; Nauta, Maaike; Rapee, Ronald M; Rey, Yasmin; Schneider, Silvia; Schneider, Sophie C; Silverman, Wendy K; Thastum, Mikael; Thirlwall, Kerstin; Waite, Polly; Eley, Thalia C; Wong, Chloe C Y

    2015-12-01

    Hypothalamic-pituitary-adrenal (HPA) axis functioning has been implicated in the development of stress-related psychiatric diagnoses and response to adverse life experiences. This study aimed to investigate the association between genetic and epigenetics in HPA axis and response to cognitive behavior therapy (CBT). Children with anxiety disorders were recruited into the Genes for Treatment project (GxT, N = 1,152). Polymorphisms of FKBP5 and GR were analyzed for association with response to CBT. Percentage DNA methylation at the FKBP5 and GR promoter regions was measured before and after CBT in a subset (n = 98). Linear mixed effect models were used to investigate the relationship between genotype, DNA methylation, and change in primary anxiety disorder severity (treatment response). Treatment response was not associated with FKBP5 and GR polymorphisms, or pretreatment percentage DNA methylation. However, change in FKBP5 DNA methylation was nominally significantly associated with treatment response. Participants who demonstrated the greatest reduction in severity decreased in percentage DNA methylation during treatment, whereas those with little/no reduction in severity increased in percentage DNA methylation. This effect was driven by those with one or more FKBP5 risk alleles, with no association seen in those with no FKBP5 risk alleles. No significant association was found between GR methylation and response. Allele-specific change in FKBP5 methylation was associated with treatment response. This is the largest study to date investigating the role of HPA axis related genes in response to a psychological therapy. Furthermore, this is the first study to demonstrate that DNA methylation changes may be associated with response to psychological therapies in a genotype-dependent manner. © 2015 The Authors. Depression and Anxiety published by Wiley Periodicals, Inc.

  17. Blunted HPA Axis Activity in Suicide Attempters Compared to those at High Risk for Suicidal Behavior.

    Science.gov (United States)

    Melhem, Nadine M; Keilp, John G; Porta, Giovanna; Oquendo, Maria A; Burke, Ainsley; Stanley, Barbara; Cooper, Thomas B; Mann, J John; Brent, David A

    2016-05-01

    Studies looking at the relationship of the hypothalamic-pituitary-adrenal (HPA) axis to suicidal behavior and its risk factors, such as depression, childhood abuse, and impulsive aggression, report inconsistent results. These studies also do not always differentiate between subjects who go on to attempt suicide, suicidal subjects who never attempted suicide, and non-suicidal subjects with psychiatric disorders. In this study, we examined cortisol responses to an experimental stressor, the Trier Social Stress Test (TSST), in 208 offspring of parents with mood disorder. Offspring suicide attempters showed lower total cortisol output (β=-0.47, 95% CI (-0.83, -0.11), p=0.01) compared with offspring with suicide-related behavior (SRB) but never attempted, non-suicidal offspring, and a healthy control group. The result remained significant even after controlling for sex, age, race, ethnicity, site, socio-economic status, and hour of the day when the TSST was conducted. Suicide attempters also showed lower baseline cortisol before the TSST (β=-0.45, 95% CI (-0.74, -0.17), p=0.002). However, there were no significant differences between the groups on cortisol reactivity to stress (β=4.5, 95% CI (-12.9, 22), p=0.61). Although subjects with suicide attempt and SRB have similar clinical and psychosocial characteristics, this is the first study to differentiate them biologically on HPA axis indices. Blunted HPA axis activity may increase risk for suicide attempt among individuals with psychopathology by reducing their ability to respond adaptively to ongoing stressors. These results may help better identify subjects at high risk for suicidal behavior for targeted prevention and intervention efforts.

  18. A Hyperresponsive HPA Axis May Confer Resilience Against Persistent Paclitaxel-Induced Mechanical Hypersensitivity.

    Science.gov (United States)

    Kozachik, Sharon L; Page, Gayle G

    2016-05-01

    Paclitaxel (PAC) treatment is associated with persistent, debilitating neuropathic pain that affects the hands and feet. Female sex and biological stress responsivity are risk factors for persistent pain, but it is unclear whether these important biologically based factors confer risk for PAC-induced neuropathic pain. To determine the relative contributions of sex and hypothalamic-pituitary-adrenal (HPA)-axis stress responsivity to PAC-induced mechanical hypersensitivity, we employed a PAC protocol consisting of three, 2-week cycles of every-other-day doses of PAC 1 mg/kg versus saline (Week 1) and recovery (Week 2), totaling 42 days, in mature male and female Fischer 344, Lewis, and Sprague Dawley (SD) rats, known to differ in HPA axis stress responsivity. Mechanical sensitivity was operationalized using von Frey filaments, per the up-down method. Among PAC-injected rats, SD rats exhibited significantly greater mechanical hypersensitivity relative to accumulative PAC doses compared to Fischer 344 rats. Lewis rats were not significantly different in mechanical hypersensitivity from SD or Fischer 344 rats. At the end of the protocol, PAC-injected SD rats exhibited profound mechanical hypersensitivity, whereas the PAC-injected Fischer 344 rats appeared relatively resilient to the long-term effects of PAC and exhibited mechanical sensitivity that was not statistically different from their saline-injected counterparts. Sex differences were mixed and noted only early in the PAC protocol. Moderate HPA axis stress responsivity may confer additional risk for the painful effects of PAC. If these findings hold in humans, clinicians may be better able to identify persons who may be at increased risks for developing neuropathic pain during PAC therapy.

  19. Childhood trauma and HPA axis functionality in offspring of bipolar parents.

    Science.gov (United States)

    Schreuder, Merel M; Vinkers, Christiaan H; Mesman, Esther; Claes, Stephan; Nolen, Willem A; Hillegers, Manon H J

    2016-12-01

    Children of a parent with bipolar disorder (bipolar offspring) have an increased risk for mood disorders. While genetic factors play a significant role in this population, susceptibility to environmental stress may also significantly contribute to this vulnerability for mood disorders. Childhood trauma has consistently been found to increase the risk for mood disorders, with persisting consequences for hypothalamic-pituitary-adrenal (HPA) axis functionality. However, it is currently unknown whether childhood trauma specifically affects HPA axis activity in individuals with a familial risk for bipolar disorder. Therefore, we investigated the effects of childhood trauma on daytime and evening cortisol levels and dexamethasone suppression in bipolar offspring (N=70) and healthy controls (N=44). In our study we found no significant differences in daytime and evening cortisol levels as well as dexamethasone suppression between bipolar offspring and healthy controls (all p-values>0.43). In contrast, childhood trauma differentially affected daytime cortisol levels in the bipolar offspring compared to healthy controls (childhood trauma X bipolar offspring interaction, β=-7.310, p=0.0414) with an effect of childhood trauma on daytime cortisol in bipolar offspring at trend level (p=0.058). In the bipolar offspring group, lifetime or current psychiatric diagnoses, and stressful life events separately did not affect cortisol levels or dexamethasone suppression (all p-values>p=0.50). These findings were independent of current or lifetime psychiatric diagnosis. In conclusion, trauma-related changes in daytime HPA axis activity appear to be a specific trait in bipolar offspring who have increased risk for mood disorders compared to healthy individuals.

  20. What can HPA axis-linked genes tell us about anxiety disorders in adolescents?

    Directory of Open Access Journals (Sweden)

    Andressa Bortoluzzi

    2015-12-01

    Full Text Available Introduction: Anxiety disorders (AD share features of both anxiety and fear linked to stress response. The hypothalamic-pituitary-adrenal (HPA axis is considered the core biological pathway of the stress system and it is known that an inappropriate response to environmental stimuli may be related to individual genetic vulnerability in HPA-linked genes. Despite the biological plausibility of a relationship between the HPA axis and AD, few studies have investigated associations between genetic polymorphisms linked to the HPA axis and this complex disorder. Objective: To investigate whether AD are associated with genetic polymorphisms in HPA-linked genes in adolescents. Methods: Our study consisted of a cross-sectional evaluation of a community sample comprising a total of 228 adolescents (131 cases of AD. We extracted DNA from saliva and genotyped polymorphisms in HPA-linked genes (FKBP5: rs3800373, rs9296158, rs1360780, rs9470080 and rs4713916; NR3C1: rs6198; CRHR1: rs878886; and SERPINA6: rs746530 with real time polymerase chain reaction (PCR. The instruments used to diagnose and assess the severity of AD were the Schedule for Affective Disorder and Schizophrenia for School-Age Children - Present and Lifetime (K-SADS-PL and the Screen for Child and Anxiety related Emotional Disorders (SCARED. Results: We failed to detect any associations between AD and genetic polymorphisms in HPA-linked genes (p > 0.05. Conclusion: To our knowledge, this is the first study evaluating these specific polymorphisms in relation to AD in adolescents, which encourages us to design further research on the subject.

  1. Dysregulation of the HPA axis as a core pathophysiology mediating co-morbid depression in neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Xin eDu

    2015-03-01

    Full Text Available There is increasing evidence of prodromal manifestation of neuropsychiatric symptoms in a variety of neurodegenerative diseases such as Parkinson’s disease and Huntington’s disease. These affective symptoms may be observed many years before the core diagnostic symptoms of the neurological condition. It is becoming more apparent that depression is a significant modifying factor of the trajectory of disease progression, and even treatment outcomes. It is therefore crucial that we understand the potential pathophysiologies related to the primary condition, which could contribute to the development of depression. The hypothalamic-pituitary-adrenal (HPA axis is a key neuroendocrine signaling system involved in physiological homeostasis and stress response. Disturbances of this system lead to severe hormonal imbalances, and the majority of such patients also present with behavioural deficits and/or mood disorders. Dysregulation of the HPA axis is also strongly implicated in the pathology of major depressive disorder. Consistent with this, anti-depressant drugs such as the selective serotonin reuptake inhibitors (SSRI have been shown to alter HPA axis activity. In this review, we will summarize the current state of knowledge regarding HPA axis pathology in Alzheimer’s, Parkinson’s and Huntington’s diseases, differentiating between prodromal and later stages of disease progression where possible. Both clinical and preclinical evidence will be examined, but we highlight animal model studies as being particularly useful for uncovering novel mechanisms of pathology related to co-morbid mood disorders. Finally, we purpose utilizing the pre-clinical evidence to better inform prospective, intervention studies.

  2. HPA axis reactivity to pharmacologic and psychological stressors in euthymic women with histories of postpartum versus major depression.

    Science.gov (United States)

    Ferguson, Elizabeth H; Di Florio, Arianna; Pearson, Brenda; Putnam, Karen T; Girdler, Susan; Rubinow, David R; Meltzer-Brody, Samantha

    2017-03-01

    It is unclear whether women with a history of postpartum depression (PPD) have residual, abnormal hypothalamic-pituitary-adrenal (HPA) axis reactivity, as has been reported in major depression (MDD). Further unclear is whether the abnormalities in HPA axis reactivity associated with MDD represent a stable, underlying predisposition or a state-dependent phenomenon. This study sought the following: (1) to determine if euthymic postpartum women with a history of depression have an abnormal HPA axis reactivity to pharmacologic and psychological challenges and (2) to compare HPA reactivity in women with histories of PPD versus MDD. As a secondary objective, we wanted to determine the influence of trauma history on HPA axis function. Forty-five parous (12-24 months postpartum), euthymic women with history of MDD (n = 15), PPD (n = 15), and controls (n = 15) completed pharmacologic (dexamethasone/corticotropin-releasing hormone (CRH) test [DEX/CRH]) and psychological (Trier social stress test [TSST]) challenges during the luteal phase. Outcome measures were cortisol and adrenocorticotropic hormone (ACTH) response after DEX/CRH, and blood pressure, heart rate, epinephrine, norepinephrine, and cortisol response during the TSST. All groups had robust cortisol and ACTH response to DEX/CRH and cortisol response to TSST. Groups did not differ significantly in cortisol or ACTH response to DEX/CRH or in blood pressure, heart rate, epinephrine, norepinephrine, or cortisol response to TSST. Cortisol/ACTH ratio did not differ significantly between groups. Trauma history was associated with decreased cortisol response to DEX/CRH in women with histories of MDD, which was not significant after correction (F 8,125, p = 0.02, Greenhouse-Geisser corrected p = 0.11). Currently euthymic women with histories of MDD or PPD did not demonstrate residual abnormal stress responsivity following administration of either a pharmacologic or psychological stressor.

  3. Activation of ATP-sensitive potassium channel by iptakalim normalizes stress-induced HPA axis disorder and depressive behaviour by alleviating inflammation and oxidative stress in mouse hypothalamus.

    Science.gov (United States)

    Zhao, Xiao-Jie; Zhao, Zhan; Yang, Dan-Dan; Cao, Lu-Lu; Zhang, Ling; Ji, Juan; Gu, Jun; Huang, Ji-Ye; Sun, Xiu-Lan

    2017-02-01

    Stress-induced disturbance of the hypothalamic-pituitary-adrenal (HPA) axis is strongly implicated in incidence of mood disorders. A heightened neuroinflammatory response and oxidative stress play a fundamental role in the dysfunction of the HPA axis. We have previously demonstrated that iptakalim (Ipt), a new ATP-sensitive potassium (K-ATP) channel opener, could prevent oxidative injury and neuroinflammation against multiple stimuli-induced brain injury. The present study was to demonstrate the impacts of Ipt in stress-induced HPA axis disorder and depressive behavior. We employed 2 stress paradigms: 8 weeks of continuous restraint stress (chronic restraint stress, CRS) and 2h of restraint stress (acute restraint stress, ARS), to mimic both chronic stress and severe acute stress. Prolonged (4 weeks) and short-term (a single injection) Ipt treatment was administered 30min before each stress paradigm. We found that HPA axis was altered after stress, with different responses to CRS (lower ACTH and CORT, higher AVP, but normal CRH) and ARS (higher CRH, ACTH and CORT, but normal AVP). Both prolonged and short-term Ipt treatment normalized stress-induced HPA axis disorders and abnormal behaviors in mice. CRS and ARS up-regulated mRNA levels of inflammation-related molecules (TNFα, IL-1β, IL-6 and TLR4) and oxidative stress molecules (gp91phox, iNOS and Nrf2) in the mouse hypothalamus. Double immunofluorescence showed CRS and ARS increased microglia activation (CD11b and TNFα) and oxidative stress in neurons (NeuN and gp91phox), which were alleviated by Ipt. Therefore, the present study reveals that Ipt could prevent against stress-induced HPA axis disorders and depressive behavior by alleviating inflammation and oxidative stress in the hypothalamus.

  4. Enhancing offspring hypothalamic-pituitary-adrenal (HPA regulation via systematic neonatal novelty exposure: the influence of maternal HPA function

    Directory of Open Access Journals (Sweden)

    Sarah M. Dinces

    2014-06-01

    Full Text Available In the rat, repeated brief exposures to novelty early in life can induce long-lasting enhancements in adult cognitive, social, emotional, and neuroendocrine function. Family-to-family variations in these intervention effects on adult offspring are predicted by the mother’s ability to mount a rapid corticosterone (CORT response to the onset of an acute stressor. Here, in Long-Evans rats, we investigated whether neonatal and adulthood novelty exposure, each individually and in combination, can enhance offspring HPA regulation. Using a 2x2 within-litter design, one half of each litter were exposed to a relatively novel non-home environment for 3-min (Neo_Novel daily during infancy (PND1-21 and the other half of the litter remained in the home cage (Neo_Home; we further exposed half of these two groups to early adulthood (PND54-63 novelty exposure in an open field and the remaining siblings stayed in their home cages. Two aspects of HPA regulation were assessed: the ability to maintain a low level of resting CORT (CORTB and the ability to mount a large rapid CORT response (CORTE to the onset of an acute stressor. Assessment of adult offspring’s ability to regulate HPA regulation began at 370 days of age. We further investigated whether the novelty exposure effects on offspring HPA regulation are sensitive to the context of maternal HPA regulation by assessing maternal HPA regulation similarly beginning 7 days after her pups were weaned. We found that at the population level, rats receiving neonatal, but not early adulthood exposure or both, showed a greater rapid CORTE than their home-staying siblings. At the individual family level, these novelty effects are positively associated with maternal CORTE. These results suggest that early experience of novelty can enhance the offspring’s ability to mount a rapid response to environmental challenge and the success of such early life intervention is critically dependent upon the context of maternal HPA regulation.

  5. Bioactive compounds from Paecilomyces tenuipes regulating the function of the hypothalamo-hypophyseal system axis in chronic unpredictable stress rats

    Institute of Scientific and Technical Information of China (English)

    YIN Yan-yan; MING Liang; ZHENG Li-fang; KAN Hong-wei; LI Chun-ru; LI Wei-ping

    2007-01-01

    Background A bioactive compound from Paecilomyces tenuipes (BGPT) has an inhibitory effect on monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B) in vitro and in vivo, which indicates BCPT may be a potential antidepressant. In this study we aimed to study the antidepressant effects of BCPT in the chronic unpredictable stress(CUS) model in rats and explore underlying mechanisms in the hypothalamic-pituitary-adrenal (HPA) axis.Methods The antidepressant effects of BCPT were studied in the chronic unpredictable stress model in rats. Animals were housed isolated, except the control group. Rats were exposed daily to different random stressors from day 1 to 21.Awarding response was detected by calculating the 24-hour consumption of sucrose water. Cortisol (CORT) and adrenocorticotropic hormone (ATCH) contents in serum and arginine vasopressin (AVP) contents in the pituitary body were detected by radio immunoassays. Total RNA of hippocampus or hypothalamus was extracted and subjected to reverse transcription-polymerase chain reaction (RT-PCR) for the measurement of corticotrophin releasing hormone(CRH) mRNA or mineralocorticoid receptor (MR) mRNA and glucocorticoid receptor (GR) mRNA levels. Statistical analyses were performed using one way analysis of variance (ANOVA) followed by Student-Newman-Keuls (SNK) test.Results Chronic unpredictable stress resulted in reduction of sensitivity to reward and abnormality in the HPA axis in the animal model. BCPT improved the reward reaction as measured by increasing sucrose consumption, remarkably reduced serum CORT and ACTH levels and the AVP content in the pituitary body in the CUS-treated rats, decreased the expression of CRH mRNA, enhanced the expression of hippocampus MR mRNA, GR mRNA and decreased the ratio of MR/GR.Conclusions BCPT has potentially antidepressant-like activity and normalized the HPA axis hyperactivity in a CUS model of depression in rats. This may be an important mechanism of its antidepressant effect.

  6. The Defecation Index as a Measure of Emotionality: Questions Raised by HPA Axis and Prolactin Response to Stress in the Maudsley Model.

    Science.gov (United States)

    Blizard, David A; Eldridge, J Charles; Jones, Byron C

    2015-05-01

    The Maudsley Reactive and Maudsley Non-Reactive strains have been selectively bred for differences in open-field defecation (OFD), a putative index of stress. We investigated whether variations in the hypothalamic-pituitary-adrenal (HPA) axis are correlated with strain differences in OFD in the Maudsley model. Exposure to the open-field test did not result in increases in ACTH in male rats of either strain and there were no strain differences in the large increases in ACTH and corticosteroid that occurred in response to intermittent footshock. Parallel studies of prolactin showed that Maudsley Reactive rats had greater response to the open-field and to footshock than Maudsley Non-Reactive rats. The lack of correlation between strain differences in OFD and reactivity of the HPA axis is consistent with the idea that HPA response to stress and OFD reflect the output of different neural systems and that individual differences in emotionality, as indexed by OFD do not influence other measures of stress-reactivity in a simple manner, if at all. The reactivity of the prolactin system to the open-field test and lack of response of ACTH to the same situation is consistent with the idea that the prolactin system is sensitive to lower levels of stress than the HPA axis, a finding at variance with the presumed extreme sensitivity of the latter system. Earlier comparisons of the HPA axis in these strains implicate local factors such as neuropeptide-Y peptide in the adrenal in attenuating the response of the adrenal cortex to ACTH and hints at the complexity of regulation of the HPA axis.

  7. Research development of interfered drugs for the dysregulation of HPA axis%HPA轴功能紊乱干预药物的研究进展

    Institute of Scientific and Technical Information of China (English)

    王晓丽; 贾正平; 张汝学

    2013-01-01

    目的对近年来基于下丘脑-垂体-肾上腺(hypothalamic-pituitary-adrenal ,HPA)轴功能调节治疗2型糖尿病和其他代谢疾病的药物做以综述,为H PA轴功能紊乱引起的相关疾病的治疗提供理论参考。方法查阅国内外文献,分析、总结 H PA轴功能紊乱干预药物的研究现状和研究前景。结果 HPA轴功能紊乱,尤其是 HPA轴功能亢进在2型糖尿病、抑郁症等疾病的发病过程中发挥重要作用;目前有以下几类通过作用于HPA轴不同靶点调节HPA轴功能的药物,即11β-HSD1抑制剂、糖皮质激素受体拮抗剂、多巴胺受体拮抗剂和选择性5-H T再摄取抑制剂等,具体机制还有待进一步阐明。结论通过调节H PA轴活性有可能达到预防和治疗2型糖尿病及其他相关疾病的目的。%Objective To review the recent researches of drugs based on the regulation of hypothalamic-pituitary-adrenal (HPA) ax-is for treating type 2 diabetes mellitus and other metabolic diseases ,and to provide a theoretical reference for curing diseases which resulted in the dysregulation of HPA axis .Method The recent literatures were scanned ,and the current study situation and pros-pect of interfered drugs for the dysregulation of HPA axis were analyzed and summarized .Results The dysregulation of HPA ax-is ,especially the hyperactivity of HPA axis ,takes an important part in the pathogenesy of type 2 diabetes mellitus ,depression , and other diseases .Currently ,there are some drugs which may be used to regulate the action of HPA axis ,such as 11β-HSD1 in-hibitors ,glucocorticoid receptor antagonists ,dopamine receptor antagonists ,selective 5-HT reuptake inhibitors and so on .but the mechanism needs further to clarify .Conclusion It is possible that type 2 diabetes and other related diseases may be prevented and treated through modulating the activity of HPA axis .

  8. Immediate effects of maternal deprivation on the (reactivity of the HPA axis differ in CD1 and C57Bl/6J mouse pups

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    Nikolaos P Daskalakis

    2014-11-01

    Full Text Available The postnatal development of the mouse is characterised by a period of hypo-responsiveness of the hypothalamic-pituitary-adrenal (HPA axis to mild stressors. Maternal deprivation (MD during this period can disrupt the quiescence of the HPA-axis. The present study examined the influence of strain (outbred CD1 versus inbred C57BL/6J mice on some central and peripheral components of the HPA-axis in neonatal mice (5 day-old in the presence of their mother or after 24 h MD (on postnatal day 4 under basal or mild stressful conditions. In the presence of the dam, adrenal corticosterone (CORT secretion was low in both mouse strains. Compared to CD1 mice, C57BL/6J had lower CORT levels associated with higher ACTH levels and ACTH/CORT ratio (i.e., lower adrenal sensitivity to ACTH, and higher glucocorticoid receptor (GR mRNA expression in the paraventricular nucleus. Although MD disinhibited the HPA-axis in both strains as reflected by increased basal CORT and ACTH, we found a strain-dependent pattern. MD increased CORT more in C57BL/6J, compared to CD1 mice, together with a lower ACTH/CORT ratio (i.e., higher adrenal sensitivity to ACTH, while GR mRNA was no longer different in the two strains. However, this increased adrenal sensitivity in maternally deprived C57BL/6J mice was not reflected in their CORT response to a subsequent novelty stressor, possibly due to a MD-induced ceiling effect in their steroidogenic capacity.In conclusion, the immediate outcome of MD depends on the genetic background of the mother-infant dyad, suggesting that maybe also the outcome in later-life cannot be generalized. genetic background of the mother-infant dyad, predicting that the outcome in later-life cannot be generalized.

  9. Developmental minocycline treatment reverses the effects of neonatal immune activation on anxiety- and depression-like behaviors, hippocampal inflammation, and HPA axis activity in adult mice.

    Science.gov (United States)

    Majidi, Jafar; Kosari-Nasab, Morteza; Salari, Ali-Akbar

    2016-01-01

    Neonatal infection is associated with increased lifetime risk for neuropsychiatric disorders including anxiety and depression, with evidence showing that dysregulation of the hypothalamic-pituitary-adrenal-(HPA)-axis system may be partly responsible. Preclinical and clinical studies demonstrate that minocycline exhibits antidepressant effects through inhibition of microglial activation and anti-inflammatory actions, and of interest is that recent studies suggest that minocycline alleviates the behavioral abnormalities induced by early-life insults. The current study was designed to determine if developmental minocycline treatment attenuates the neonatal immune activation-induced anxiety- and depression-like symptoms and HPA-axis-dysregulation later in life. To this end, neonatal mice were treated to either lipopolysaccharide or saline on postnatal days (PND) 3-5, then dams during lactation (PND 6-20) and male offspring during adolescence (PND 21-40) received oral administration of minocycline or water via regular drinking bottles. Anxiety- and depression-like behaviors, HPA-axis-reactivity (corticosterone), and hippocampal inflammation (TNF-α and IL-1β) after exposure to stress were evaluated. The results indicated that neonatal immune activation resulted in increased anxiety and depression-like symptoms, HPA-axis-hyperactivity, and elevated the levels of TNF-α and IL-1β in the hippocampus in response to stress in adulthood. Interestingly, developmental minocycline treatment significantly reduced the abnormalities induced by neonatal inflammation in adult mice. In addition, minocycline, regardless of postnatal inflammation, did not have any detrimental effects on the above measured parameters. Considering that minocycline is currently under exploration as an alternative or adjunctive therapy for reducing the symptoms of neurological disorders, our findings suggest that minocycline during development can decrease the behavioral abnormalities induced by early

  10. Stress in adolescence and drugs of abuse in rodent models: Role of dopamine, CRF, and HPA axis

    Science.gov (United States)

    Burke, Andrew R.; Miczek, Klaus A.

    2014-01-01

    Rationale Research on adolescence and drug abuse increased substantially in the past decade. However, drug-addiction related behaviors following stressful experiences during adolescence are less studied. We focus on rodent models of adolescent stress cross-sensitization to drugs of abuse. Objectives Review the ontogeny of behavior, dopamine, corticotropin-releasing factor (CRF), and the hypothalamic pituitary adrenal (HPA) axis in adolescent rodents. We evaluate evidence that stressful experiences during adolescence engender hypersensitivity to drugs of abuse and offer potential neural mechanisms. Results and Conclusions Much evidence suggests that final maturation of behavior, dopamine systems, and HPA axis occurs during adolescence. Stress during adolescence increases amphetamine- and ethanol-stimulated locomotion, preference, and self-administration under many conditions. The influence of adolescent stress on subsequent cocaine- and nicotine-stimulated locomotion and preference is less clear. The type of adolescent stress, temporal interval between stress and testing, species, sex, and the drug tested are key methodological determinants for successful cross-sensitization procedures. The sensitization of the mesolimbic dopamine system is proposed to underlie stress cross-sensitization to drugs of abuse in both adolescents and adults through modulation by CRF. Reduced levels of mesocortical dopamine appear to be a unique consequence of social stress during adolescence. Adolescent stress may reduce the final maturation of cortical dopamine through D2 dopamine receptor regulation of dopamine synthesis or glucocorticoid-facilitated pruning of cortical dopamine fibers. Certain rodent models of adolescent adversity are useful for determining neural mechanisms underlying the cross-sensitization to drugs of abuse. PMID:24370534

  11. Decreased daytime illumination leads to anxiety-like behaviors and HPA axis dysregulation in the diurnal grass rat (Arvicanthis niloticus)

    Science.gov (United States)

    Ikeno, Tomoko; Deats, Sean P.; Soler, Joel; Lonstein, Joseph S.; Yan, Lily

    2016-01-01

    The impact of ambient light on mood and anxiety is best exemplified in seasonal affective disorder, in which patients experience depression and anxiety in winter when there is less light in the environment. However, the brain mechanisms underlying light-dependent changes in affective state remain unclear. Our previous work revealed increased depression-like behaviors in the diurnal Nile grass rat (Arvicanthis niloticus) housed in a dim light-dark (dim-LD) cycle as compared to the controls housed in a bright light-dark (bright-LD) condition. As depression is often comorbid with anxiety and is associated with dysregulation of the body's stress response system, the present study examined the anxiety-like behaviors as well as indicators of the hypothalamic-pituitary-adrenal (HPA) axis functioning in the grass rats. Animals housed in dim-LD showed increased anxiety-like behaviors compared to bright-LD controls, as revealed by fewer entries and less time spent at the center in the open field test and more marbles buried during the marble-burying test. Following the marble-burying test, dim-LD animals showed higher plasma corticosterone (CORT) levels and hippocampal Fos expression. Although the daily CORT rhythm was comparable between bright-LD and dim-LD groups, the day/night variation of corticotropin-releasing hormone mRNA expression in the paraventricular nucleus was diminished in dim-LD animals. In addition, glucocorticoid receptor and mineralocorticoid receptor mRNA expression were higher in the hippocampus of dim-LD animals. The results suggest that in diurnal species, reduced daytime illumination can lead to increased anxiety-like behaviors and altered HPA axis functioning, providing insights into the link between decreased environmental illumination and negative emotion. PMID:26684510

  12. Glutamatergic and HPA-axis pathway genes in bipolar disorder comorbid with alcohol- and substance use disorders.

    Science.gov (United States)

    Dalvie, Shareefa; Fabbri, Chiara; Ramesar, Raj; Serretti, Alessandro; Stein, Dan J

    2016-02-01

    Glutamatergic neurotransmission has been shown to be dysregulated in bipolar disorder (BD), alcohol use disorder (AUD) and substance use disorder (SUD). Similarly, disruption in the hypothalamic-pituitary-adrenal (HPA)-axis has also been observed in these conditions. BD is often comorbid with AUD and SUD. The effects of the glutamatergic and HPA systems have not been extensively examined in individuals with BD-AUD and BD-SUD comorbidity. The aim of this investigation was to determine whether variants in the glutamatergic pathway and HPA-axis are associated with BD-AUD and BD-SUD comorbidity. The research cohort consisted of 498 individuals with BD type I from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). A subset of the cohort had comorbid current AUD and current SUD. A total of 1935 SNPs from both the glutamatergic and HPA pathways were selected from the STEP-BD genome-wide dataset. To identify population stratification, IBS clustering was performed using the program Plink 1.07. Single SNP association and gene-based association testing were conducted using logistic regression. A pathway analysis of glutamatergic and HPA genes was performed, after imputation using IMPUTE2. No single SNP was associated with BD-AUD or BD-SUD comorbidity after correction for multiple testing. However, from the gene-based analysis, the gene PRKCI was significantly associated with BD-AUD. The pathway analysis provided overall negative findings, although several genes including GRIN2B showed high percentage of associated SNPs for BD-AUD. Even though the glutamatergic and HPA pathways may not be involved in BD-AUD and BD-SUD comorbidity, PRKCI deserves further investigation in BD-AUD.

  13. Decreased daytime illumination leads to anxiety-like behaviors and HPA axis dysregulation in the diurnal grass rat (Arvicanthis niloticus).

    Science.gov (United States)

    Ikeno, Tomoko; Deats, Sean P; Soler, Joel; Lonstein, Joseph S; Yan, Lily

    2016-03-01

    The impact of ambient light on mood and anxiety is best exemplified in seasonal affective disorder, in which patients experience depression and anxiety in winter when there is less light in the environment. However, the brain mechanisms underlying light-dependent changes in affective state remain unclear. Our previous work revealed increased depression-like behaviors in the diurnal Nile grass rat (Arvicanthis niloticus) housed in a dim light-dark (dim-LD) cycle as compared to the controls housed in a bright light-dark (bright-LD) condition. As depression is often comorbid with anxiety and is associated with dysregulation of the body's stress response system, the present study examined the anxiety-like behaviors as well as indicators of the hypothalamic-pituitary-adrenal (HPA) axis functioning in the grass rats. Animals housed in dim-LD showed increased anxiety-like behaviors compared to bright-LD controls, as revealed by fewer entries and less time spent at the center in the open field test and more marbles buried during the marble-burying test. Following the marble-burying test, dim-LD animals showed higher plasma corticosterone (CORT) levels and hippocampal Fos expression. Although the daily CORT rhythm was comparable between bright-LD and dim-LD groups, the day/night variation of corticotropin-releasing hormone mRNA expression in the paraventricular nucleus was diminished in dim-LD animals. In addition, glucocorticoid receptor and mineralocorticoid receptor mRNA expression were higher in the hippocampus of dim-LD animals. The results suggest that in diurnal species, reduced daytime illumination can lead to increased anxiety-like behaviors and altered HPA axis functioning, providing insights into the link between decreased environmental illumination and negative emotion.

  14. NF-kappaB activity affects learning in aversive tasks: possible actions via modulation of the stress axis.

    Science.gov (United States)

    Lehmann, Michael L; Brachman, Rebecca A; Listwak, Samuel J; Herkenham, Miles

    2010-08-01

    The role of altered activity of nuclear factor kappaB (NF-kappaB) in specific aspects of motivated behavior and learning and memory was examined in mice lacking the p50 subunit of the NF-kappaB/rel transcription factor family. Nfkb1-deficient mice are unable to produce p50 and show specific susceptibilities to infections and inflammatory challenges, but the behavioral phenotype of such mice has been largely unexamined, owing in large part to the lack of understanding of the role of NF-kappaB in nervous system function. Here we show that Nfkb1 (p50) knockout mice more rapidly learned to find the hidden platform in the Morris water maze than did wildtype mice. The rise in plasma corticosterone levels after the maze test was greater in p50 knockout than in wildtype mice. In the less stressful Barnes maze, which tests similar kinds of spatial learning, the p50 knockout mice performed similarly to control mice. Adrenalectomy with corticosterone replacement eliminated the differences between p50 knockout and wildtype mice in the water maze. Knockout mice showed increased levels of basal anxiety in the open-field and light/dark box tests, suggesting that their enhanced escape latency in the water maze was due to activation of the stress (hypothalamic-pituitary-adrenal) axis leading to elevated corticosterone production by strongly but not mildly anxiogenic stimuli. The results suggest that, as in the immune system, p50 in the nervous system normally serves to dampen NF-kappaB-mediated intracellular activities, which are manifested physiologically through elevated stress responses to aversive stimuli and behaviorally in the facilitated escape performance in learning tasks.

  15. [The relationship of ultrastructure and function of hypothalamus-pituitary-adrenal axis in early stage of sepsis in rats].

    Science.gov (United States)

    Zhang, Yu-xiang; Li, Hong-shan; Ma, Peng-lin

    2011-05-01

    To observe the changes in ultrastructure and function of hypothalamic-pituitary-adrenal axis (HPAA), and to approach the relationship between them in early stage of sepsis in rats. Thirty male Sprague-Dawley (SD) rats were randomly divided into normal control group, sham group, sepsis group. The sepsis model was reproduced by cecal ligation and puncture (CLP). The rats were sacrificed after collection of blood at 6 hours after CLP, and the levels of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) in the plasma, and the corticotropin release hormone (CRH) in the tissue of hypothalamus were detected. The histopathological changes in HPAA were observed with transmission electron microscopy. The levels of ACTH and CORT in plasma, and the CRH in hypothalamus tissue of sepsis group were increased in the early stage of sepsis compared with the normal control group or sham group [ACTH (pmol/L): 5.78±0.36 vs. 1.94±0.31, 2.51±0.10; CORT (nmol/L): 88.48±4.47 vs. 22.02±1.62, 34.20±2.51; CRH (μg/L): 101.92±6.61 vs. 61.65±6.05, 66.65±4.03, PHPAA was excessively activated, and ACTH and CORT in plasma, and CRH in hypothalamus were significantly increased in early stage of sepsis. The changes in ultrastructure of HPAA were obvious, and the change in function was closely related to the ultrastructural changes.

  16. Early intervention with intranasal NPY prevents single prolonged stress-triggered impairments in hypothalamus and ventral hippocampus in male rats.

    Science.gov (United States)

    Laukova, Marcela; Alaluf, Lishay G; Serova, Lidia I; Arango, Victoria; Sabban, Esther L

    2014-10-01

    Intranasal administration of neuropeptide Y (NPY) is a promising treatment strategy to reduce traumatic stress-induced neuropsychiatric symptoms of posttraumatic stress disorder (PTSD). We evaluated the potential of intranasal NPY to prevent dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis, a core neuroendocrine feature of PTSD. Rats were exposed to single prolonged stress (SPS), a PTSD animal model, and infused intranasally with vehicle or NPY immediately after SPS stressors. After 7 days undisturbed, hypothalamus and hippocampus, 2 structures regulating the HPA axis activity, were examined for changes in glucocorticoid receptor (GR) and CRH expression. Plasma ACTH and corticosterone, and hypothalamic CRH mRNA, were significantly higher in the vehicle but not NPY-treated group, compared with unstressed controls. Although total GR levels were not altered in hypothalamus, a significant decrease of GR phosphorylated on Ser232 and increased FK506-binding protein 5 mRNA were observed with the vehicle but not in animals infused with intranasal NPY. In contrast, in the ventral hippocampus, only vehicle-treated animals demonstrated elevated GR protein expression and increased GR phosphorylation on Ser232, specifically in the nuclear fraction. Additionally, SPS-induced increase of CRH mRNA in the ventral hippocampus was accompanied by apparent decrease of CRH peptide particularly in the CA3 subfield, both prevented by NPY. The results show that early intervention with intranasal NPY can prevent traumatic stress-triggered dysregulation of the HPA axis likely by restoring HPA axis proper negative feedback inhibition via GR. Thus, intranasal NPY has a potential as a noninvasive therapy to prevent negative effects of traumatic stress.

  17. Piper sarmentosum Roxb. produces antidepressant-like effects in rodents, associated with activation of the CREB-BDNF-ERK signaling pathway and reversal of HPA axis hyperactivity.

    Science.gov (United States)

    Li, Qing; Qu, Fa-Lin; Gao, Yue; Jiang, Yi-Ping; Rahman, Khalid; Lee, Kuo-Hsiung; Han, Ting; Qin, Lu-Ping

    2017-03-06

    There are many plants of genus Piper which have been reported to induce antidepressant-like effects, Piper sarmentosum (PS) is one of them. PS is a Chinese herbal medicine and a traditional edible vegetable. In the present study, the antidepressant-like effects of PS extracts and the ethyl acetate fraction of PS extracts (PSY) were assessed using the open field test (OFT), forced swimming test (FST), and tail suspension test (TST) in mice. Furthermore, we applied a 4 consecutive weeks of chronic unpredictable mild stress (CUMS) as a model of depression in rats, followed by a sucrose preference test. Then we examined the possible mechanisms of this action. The activity of the hypothalamic-pituitary-adrenal (HPA) axis was evaluated by detecting the serum corticosterone (CORT) concentrations, and the protein expression levels of brain-derived neurotrophic factor (BDNF), the phosphorylated form CREB and ERK1/2 were detected by qRT-PCR or Western blot. The results showed that PS extracts (100, 200mg/kg) and PSY (12.5, 25, 50mg/kg) treatment produced antidepressant-like effects in mice similar to fluoxetine (20mg/kg), indicated by the reduced immobility time in the FST and TST, while both had no influence on the locomotor activity in the OFT. PSY treatment significantly increased sucrose preference and reduced serum CORT levels in CUMS rats. Moreover, PSY up-regulated BDNF protein levels, and increased CREB and ERK phosphorylation levels in the hippocampus on CUMS rats. These findings suggest that the antidepressant-like effects of PS extracts and PSY are mediated, at least in part, by modulating HPA axis, BDNF, CREB and ERK phosphorylation and expression in the hippocampus. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  18. A short-term extremely low frequency electromagnetic field exposure increases circulating leukocyte numbers and affects HPA-axis signaling in mice.

    Science.gov (United States)

    de Kleijn, Stan; Ferwerda, Gerben; Wiese, Michelle; Trentelman, Jos; Cuppen, Jan; Kozicz, Tamas; de Jager, Linda; Hermans, Peter W M; Verburg-van Kemenade, B M Lidy

    2016-10-01

    There is still uncertainty whether extremely low frequency electromagnetic fields (ELF-EMF) can induce health effects like immunomodulation. Despite evidence obtained in vitro, an unambiguous association has not yet been established in vivo. Here, mice were exposed to ELF-EMF for 1, 4, and 24 h/day in a short-term (1 week) and long-term (15 weeks) set-up to investigate whole body effects on the level of stress regulation and immune response. ELF-EMF signal contained multiple frequencies (20-5000 Hz) and a magnetic flux density of 10 μT. After exposure, blood was analyzed for leukocyte numbers (short-term and long-term) and adrenocorticotropic hormone concentration (short-term only). Furthermore, in the short-term experiment, stress-related parameters, corticotropin-releasing hormone, proopiomelanocortin (POMC) and CYP11A1 gene-expression, respectively, were determined in the hypothalamic paraventricular nucleus, pituitary, and adrenal glands. In the short-term but not long-term experiment, leukocyte counts were significantly higher in the 24 h-exposed group compared with controls, mainly represented by increased neutrophils and CD4 ± lymphocytes. POMC expression and plasma adrenocorticotropic hormone were significantly lower compared with unexposed control mice. In conclusion, short-term ELF-EMF exposure may affect hypothalamic-pituitary-adrenal axis activation in mice. Changes in stress hormone release may explain changes in circulating leukocyte numbers and composition. Bioelectromagnetics. 37:433-443, 2016. © 2016 The Authors. Bioelectromagnetics Published by Wiley Periodicals, Inc.

  19. Adolescent Personality : Associations With Basal, Awakening, and Stress-Induced Cortisol Responses

    NARCIS (Netherlands)

    Laceulle, Odilia M.; Nederhof, Esther; van Aken, Marcel A. G.; Ormel, Johan

    2015-01-01

    The purpose of the present study was to investigate the associations between personality facets and hypothalamic-pituitary-adrenal (HPA) axis functioning. Previous studies have mainly focussed on stress-induced HPA-axis activation. We hypothesized that other characteristics of HPA-axis functioning w

  20. Cortisol regulation in 12-month-old human infants: Associations with the infants' early history of breastfeeding and co-sleeping

    NARCIS (Netherlands)

    Beijers, R.; Riksen-Walraven, J.M.A.; Weerth, C. de

    2013-01-01

    Experiences during early life are suggested to affect the physiological systems underlying stress responses, including the hypothalamic-pituitary-adrenal axis (HPA axis). While stressful early experiences have been associated with dysregulated HPA-axis functioning, positive early experiences, i.e. h

  1. Heat stress impairs performance parameters, induces intestinal injury, and decreases macrophage activity in broiler chickens.

    Science.gov (United States)

    Quinteiro-Filho, W M; Ribeiro, A; Ferraz-de-Paula, V; Pinheiro, M L; Sakai, M; Sá, L R M; Ferreira, A J P; Palermo-Neto, J

    2010-09-01

    Studies on environmental consequences of stress on animal production have grown substantially in the last few years for economic and animal welfare reasons. Physiological, hormonal, and immunological deficits as well as increases in animals' susceptibility to diseases have been reported after different stressors in broiler chickens. The aim of the current experiment is to describe the effects of 2 different heat stressors (31 +/- 1 and 36 +/- 1 degrees C/10 h per d) applied to broiler chickens from d 35 to 42 of life on the corticosterone serum levels, performance parameters, intestinal histology, and peritoneal macrophage activity, correlating and discussing the obtained data under a neuroimmune perspective. In our study, we demonstrated that heat stress (31 +/- 1 and 36 +/- 1 degrees C) increased the corticosterone serum levels and decreased BW gain and food intake. Only chickens submitted to 36 +/- 1 degrees C, however, presented a decrease in feed conversion and increased mortality. We also showed a decrease of bursa of Fabricius (31 +/- 1 and 36 +/- 1 degrees C), thymus (36 +/- 1 degrees C), and spleen (36 +/- 1 degrees C) relative weights and of macrophage basal (31 +/- 1 and 36 +/- 1 degrees C) and Staphylococcus aureus-induced oxidative burst (31 +/- 1 degrees C). Finally, mild multifocal acute enteritis characterized by an increased presence of lymphocytes and plasmocytes within the jejunum's lamina propria was also observed. The stress-induced hypothalamic-pituitary-adrenal axis activation was taken as responsible for the negative effects observed on the chickens' performance and immune function and also the changes of the intestinal mucosa. The present obtained data corroborate with others in the field of neuroimmunomodulation and open new avenues for the improvement of broiler chicken welfare and production performance.

  2. Early-life stress and HPA axis trigger recurrent adulthood depression.

    Science.gov (United States)

    Juruena, Mario F

    2014-09-01

    It is now broadly accepted that psychological stress may change the internal homeostatic state of an individual. During acute stress, adaptive physiological responses occur, which include hyperactivity of the HPA axis. Whenever there is an acute interruption of this balance, illness may result. The social and physical environments have an enormous impact on our physiology and behavior, and they influence the process of adaptation or 'allostasis'. It is correct to state that at the same time that our experiences change our brain and thoughts, namely, changing our mind, we are changing our neurobiology. Increased adrenocortical secretion of hormones, primarily cortisol in major depression, is one of the most consistent findings in neuropsychiatry. A significant percentage of patients with major depression have been shown to exhibit increased concentrations of cortisol, an exaggerated cortisol response to adrenocorticotropic hormone, and an enlargement of both the pituitary and adrenal glands. The maintenance of the internal homeostatic state of an individual is proposed to be based on the ability of circulating glucocorticoids to exert negative feedback on the secretion of hypothalamic-pituitary-adrenal (HPA) hormones through binding to mineralocorticoid (MR) and glucocorticoid (GR) receptors limiting the vulnerability to diseases related to psychological stress in genetically predisposed individuals. The HPA axis response to stress can be thought of as a mirror of the organism's response to stress: acute responses are generally adaptive, but excessive or prolonged responses can lead to deleterious effects. Evidence indicates that early-life stress can induce persistent changes in the ability of the HPA axis to respond to stress in adulthood. These abnormalities appear to be related to changes in the ability of hormones to bind to GR and MR receptors. First episodes may begin with an environmental stressor, but if the cycles continue or occur unchecked, the brain

  3. Sleep and 24-h activity rhythms in relation to cortisol change after a very low-dose of dexamethasone

    NARCIS (Netherlands)

    Luik, Annemarie I; Direk, Neşe; Zuurbier, Lisette A; Hofman, Albert; Van Someren, Eus J W; Tiemeier, Henning

    The hypothalamic-pituitary-adrenal (HPA) axis plays an important role in sleep. Nevertheless, the association of sleep and its 24-h organization with negative feedback control of the HPA axis has received limited attention in population-based studies. We explored this association in 493 middle-aged

  4. Emotional attentional control predicts changes in diurnal cortisol secretion following exposure to a prolonged psychosocial stressor

    OpenAIRE

    Lenaert, Bert; Barry, Tom; Schruers, Koen; Vervliet, Bram; Hermans, Dirk

    2015-01-01

    Hypothalamic-pituitary-adrenal (HPA) axis irregularities have been associated with several psychological disorders. Hence, the identification of individual difference variables that predict variations in HPA-axis activity represents an important challenge for psychiatric research. We investigated whether self-reported attentional control in emotionally demanding situations prospectively predicted changes in diurnal salivary cortisol secretion following exposure to a prolonged psychosocial str...

  5. How stress gets under the skin: cortisol and stress reactivity in psoriasis.

    NARCIS (Netherlands)

    Evers, A.W.M.; Verhoeven, E.W.M.; Kraaimaat, F.W.; Jong, E.M.G.J. de; Brouwer, S.J.M. de; Schalkwijk, J.; Sweep, F.C.; Kerkhof, P.C.M. van de

    2010-01-01

    BACKGROUND: Psychological stressors might contribute to the severity of chronic inflammatory diseases such as psoriasis by dysregulating hypothalamic-pituitary-adrenal (HPA) axis activity. OBJECTIVES: To evaluate the role of cortisol, a key component of the HPA axis, in reaction to psychological str

  6. Damage Effects of Rat Thymus After Cranial Irradiation

    Institute of Scientific and Technical Information of China (English)

    YU; Ying-qi; WANG; Xiao; SUI; Li; KONG; Fu-quan; MA; Nan-ru

    2012-01-01

    <正>To study the damage effects of the thymus and investigate the interaction of hypothalamic- pituitary-adrenal axis (HPA axis) in neuroimmunological signaling pathway, the rat model of cranial irradiated by carbon ions was establish. By means of enzyme-linked immunoassay (Elisa), one day of post-irradiation with carbon ions, for the group of control, irradiated or drug (Longxuejie) treated,

  7. Elevated plasma arginine vasopressin levels in veterans with posttraumatic stress disorder

    NARCIS (Netherlands)

    de Kloet, C. S.; Vermetten, E.; Geuze, E.; Wiegant, V. M.; Westenberg, H. G. M.

    2008-01-01

    Background: Posttraumatic stress disorder (PTSD) is associated with altered hypothalamic-pituitary-adrenal (HPA) axis functioning. Arginine vasopressin (AVP), in conjunction with corticotrophin releasing hormone, has shown to be an important modulator of the HPA axis. In order to evaluate the effect

  8. Salivary cortisol and dehydroepiandrosterone sulfate in adolescent rape victims with post traumatic stress disorder

    NARCIS (Netherlands)

    Bicanic, Iva A. E.; Postma, Riemke M.; Sinnema, Gerben; De Roos, Carlijn; Olff, Miranda; Van Wesel, Floryt; Van de Putte, Elise M.

    2013-01-01

    Background: In chronic sexual abuse victims with post traumatic stress disorder (PTSD), the hypothalamic pituitary adrenal (HPA) axis can be dysregulated. In single rape victims, PTSD symptoms are hypothesized to function as a chronic stressor leading to similar HPA-axis dysregulation. The objective

  9. Salivary cortisol and dehydroepiandrosterone sulfate in adolescent rape victims with post traumatic stress disorder

    NARCIS (Netherlands)

    Bicanic, Iva A. E.; Postma, Riemke M.; Sinnema, Gerben; De Roos, Carlijn; Olff, Miranda; Van Wesel, Floryt; Van de Putte, Elise M.

    2013-01-01

    Background: In chronic sexual abuse victims with post traumatic stress disorder (PTSD), the hypothalamic pituitary adrenal (HPA) axis can be dysregulated. In single rape victims, PTSD symptoms are hypothesized to function as a chronic stressor leading to similar HPA-axis dysregulation. The objective

  10. Personality traits in rats predict vulnerability and resilience to developing stress-induced depression-like behaviors, HPA axis hyper-reactivity and brain changes in pERK1/2 activity.

    Science.gov (United States)

    Castro, Jorge E; Diessler, Shanaz; Varea, Emilio; Márquez, Cristina; Larsen, Marianne H; Cordero, M Isabel; Sandi, Carmen

    2012-08-01

    Emerging evidence indicates that certain behavioral traits, such as anxiety, are associated with the development of depression-like behaviors after exposure to chronic stress. However, single traits do not explain the wide variability in vulnerability to stress observed in outbred populations. We hypothesized that a combination of behavioral traits might provide a better characterization of an individual's vulnerability to prolonged stress. Here, we sought to determine whether the characterization of relevant behavioral traits in rats could aid in identifying individuals with different vulnerabilities to developing stress-induced depression-like behavioral alterations. We also investigated whether behavioral traits would be related to the development of alterations in the hypothalamic-pituitary-adrenal axis and in brain activity - as measured through phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2)--in response to an acute stressor following either sub-chronic (2 weeks) or chronic (4 weeks) unpredictable stress (CUS). Sprague-Dawley rats were characterized using a battery of behavioral tasks, and three principal traits were identified: anxiety, exploration and activity. When combined, the first two traits were found to explain the variability in the stress responses. Our findings confirm the increased risk of animals with high anxiety developing certain depression-like behaviors (e.g., increased floating time in the forced swim test) when progressively exposed to stress. In contrast, the behavioral profile based on combined low anxiety and low exploration was resistant to alterations related to social behaviors, while the high anxiety and low exploration profile displayed a particularly vulnerable pattern of physiological and neurobiological responses after sub-chronic stress exposure. Our findings indicate important differences in animals' vulnerability and/or resilience to the effects of repeated stress, particularly during initial or

  11. Methylation of HPA axis related genes in men with hypersexual disorder.

    Science.gov (United States)

    Jokinen, Jussi; Boström, Adrian E; Chatzittofis, Andreas; Ciuculete, Diana M; Öberg, Katarina Görts; Flanagan, John N; Arver, Stefan; Schiöth, Helgi B

    2017-03-10

    Hypersexual Disorder (HD) defined as non-paraphilic sexual desire disorder with components of compulsivity, impulsivity and behavioral addiction, and proposed as a diagnosis in the DSM 5, shares some overlapping features with substance use disorder including common neurotransmitter systems and dysregulated hypothalamic-pituitary-adrenal (HPA) axis function. In this study, comprising 67 HD male patients and 39 male healthy volunteers, we aimed to identify HPA-axis coupled CpG-sites, in which modifications of the epigenetic profile are associated with hypersexuality. The genome-wide methylation pattern was measured in whole blood using the Illumina Infinium Methylation EPIC BeadChip, measuring the methylation state of over 850K CpG sites. Prior to analysis, the global DNA methylation pattern was pre-processed according to standard protocols and adjusted for white blood cell type heterogeneity. We included CpG sites located within 2000bp of the transcriptional start site of the following HPA-axis coupled genes: Corticotropin releasing hormone (CRH), corticotropin releasing hormone binding protein (CRHBP), corticotropin releasing hormone receptor 1 (CRHR1), corticotropin releasing hormone receptor 2 (CRHR2), FKBP5 and the glucocorticoid receptor (NR3C1). We performed multiple linear regression models of methylation M-values to a categorical variable of hypersexuality, adjusting for depression, dexamethasone non-suppression status, Childhood Trauma Questionnaire total score and plasma levels of TNF-alpha and IL-6. Of 76 tested individual CpG sites, four were nominally significant (p<0.05), associated with the genes CRH, CRHR2 and NR3C1. Cg23409074-located 48bp upstream of the transcription start site of the CRH gene - was significantly hypomethylated in hypersexual patients after corrections for multiple testing using the FDR-method. Methylation levels of cg23409074 were positively correlated with gene expression of the CRH gene in an independent cohort of 11 healthy

  12. Personality dimensions harm avoidance and self-directedness predict the cortisol awakening response in military men

    NARCIS (Netherlands)

    Rademaker, Arthur R.; Kleber, Rolf J.; Geuze, Elbert; Vermetten, Eric

    2009-01-01

    To account for individual differences in vulnerability for stress-related disorders, studies have examined the relationship between hypothalamic-pituitary-adrenal (HPA) axis functioning and personality. The present study examined the relationship between the free fraction of cortisol in saliva after

  13. Volume of the adrenal and pituitary glands in depression

    DEFF Research Database (Denmark)

    Kessing, Lars Vedel; Willer, Inge Stoel; Knorr, Ulla

    2011-01-01

    Numerous studies have shown that the hypothalamic-pituitary-adrenal (HPA) axis is hyperactive in some depressed patients. It is unclear whether such hyperactivity results in changed volumes of the adrenal glands, pituitary gland and hypothalamus. We systematically reviewed all controlled studies ...

  14. Pituitary Volume Prospectively Predicts Internalizing Symptoms in Adolescence

    Science.gov (United States)

    Zipursky, Amy R.; Whittle, Sarah; Yucel, Murat; Lorenzetti, Valentina; Wood, Stephen J.; Lubman, Dan I.; Simmons, Julian G.; Allen, Nicholas B.

    2011-01-01

    Background: Early adolescence is a critical time for the development of both internalizing and externalizing disorders. We aimed to investigate whether pituitary volume, an index of hypothalamic-pituitary-adrenal (HPA) axis function, represents a vulnerability factor for the emergence of internalizing and externalizing symptoms during adolescence…

  15. Children with asthma have significantly lower long-term cortisol levels in their scalp hair than healthy children

    NARCIS (Netherlands)

    Kamps, Arvid W. A.; Molenmaker, Marco; Kemperman, Ramses; van der Veen, Betty S.; Bocca, Gianni; Veeger, Nic J. G. M.

    2014-01-01

    Aim: Noninvasive measurement of long-term cortisol levels is a useful way of evaluating the effect of chronic disease on the hypothalamic-pituitary-adrenal axis in children. The aim of this pilot study was to compare hair cortisol levels in children using inhaled corticosteroids for asthma and healt

  16. Chernobyl exposure as stressor during pregnancy and hormone levels in adolescent offspring

    NARCIS (Netherlands)

    Huizink, A.C.; Bartels, M.; Rose, R.J.; Pulkkinen, L.; Eriksson, C.J.P.; Kaprio, J.

    2008-01-01

    Background: Animal research suggests a programming effect of prenatal stress in the fetal period, resulting in disruptions in behavioural and neuromotor development. Physiological changes that mediate these effects include alterations in the hypothalamic-pituitary-adrenal axis and in testosterone le

  17. Chronic Psychosocial Factors and Acute Physiological Responses to Laboratory-Induced Stress in Healthy Populations: A Quantitative Review of 30 Years of Investigations

    Science.gov (United States)

    Chida, Yoichi; Hamer, Mark

    2008-01-01

    This meta-analysis included 729 studies from 161 articles investigating how acute stress responsivity (including stress reactivity and recovery of hypothalamic-pituitary-adrenal [HPA] axis, autonomic, and cardiovascular systems) changes with various chronic psychosocial exposures (job stress; general life stress; depression or hopelessness;…

  18. Global Stability in Dynamical Systems with Multiple Feedback Mechanisms

    DEFF Research Database (Denmark)

    Andersen, Morten; Vinther, Frank; Ottesen, Johnny T.

    2016-01-01

    of the system. The proof relies on the contraction mapping theorem. Applications of this type of systems are numerous in biology, e.g., models of the hypothalamic-pituitary-adrenal axis and testosterone secretion. Some results important for modelling are: 1) Existence of an attractive trapping region...

  19. Pituitary Volume Prospectively Predicts Internalizing Symptoms in Adolescence

    Science.gov (United States)

    Zipursky, Amy R.; Whittle, Sarah; Yucel, Murat; Lorenzetti, Valentina; Wood, Stephen J.; Lubman, Dan I.; Simmons, Julian G.; Allen, Nicholas B.

    2011-01-01

    Background: Early adolescence is a critical time for the development of both internalizing and externalizing disorders. We aimed to investigate whether pituitary volume, an index of hypothalamic-pituitary-adrenal (HPA) axis function, represents a vulnerability factor for the emergence of internalizing and externalizing symptoms during adolescence…

  20. Do social disadvantage and early family adversity affect the diurnal cortisol rhythm in infants? The Generation R Study

    NARCIS (Netherlands)

    Saridjan, N.S.; Huizink, A.C.; Koetsier, J.A.; Jaddoe, V.W.V.; Mackenbach, J.P.; Hofman, A.; Kirschbaum, C.; Verhulst, F.C.; Tiemeier, H.

    2010-01-01

    Dysregulation of diurnal cortisol secretion patterns may explain the link between adversities early in life and later mental health problems. However, few studies have investigated the influence of social disadvantage and family adversity on the hypothalamic-pituitary-adrenal (HPA) axis early in

  1. Cortisol administration increases hippocampal activation to infant crying in males depending on childhood neglect

    NARCIS (Netherlands)

    Bos, P.A.; Montoya, E.R.; Terburg, D.; van Honk, J.

    2014-01-01

    Animal studies show that exposure to parental neglect alters stress regulation and can lead to neural hyposensitivity or hypersensitivity in response to cortisol, most pronounced in the hippocampus. Cortisol, the end product of the hypothalamic-pituitary-adrenal (HPA) axis, has also been related to

  2. A single exposure to novelty differentially affects the accumbal dopaminergic system of apomorphine-susceptible and apomorphine-unsusceptible rats.

    NARCIS (Netherlands)

    Elst, M.C.J. van der; Verheij, M.M.M.; Roubos, E.W.; Ellenbroek, B.A.; Veening, J.G.; Cools, A.R.

    2005-01-01

    Individual differences in responses to mild, acute stressors in laboratory animals have commonly been observed in behavioural tests and at the level of hypothalamic-pituitary-adrenal axis responses. These differences are associated with dopamine transmission in the nucleus accumbens. Although the

  3. Children's Context Inappropriate Anger and Salivary Cortisol

    Science.gov (United States)

    Locke, Robin L.; Davidson, Richard J.; Kalin, Ned H.; Goldsmith, H. Hill

    2009-01-01

    Some children show emotion that is not consistent with normative appraisal of the context and can therefore be defined as context inappropriate (CI). The authors used individual growth curve modeling and hierarchical multiple regression analyses to examine whether CI anger predicts differences in hypothalamic-pituitary-adrenal axis activity, as…

  4. Markers of stress and inflammation as potential mediators of the relationship between exercise and depressive symptoms : Findings from the TRAILS study

    NARCIS (Netherlands)

    Booij, Sanne H; Bos, Elisabeth H; de Jonge, Peter; Oldehinkel, Albertine J

    2015-01-01

    The hypothalamic-pituitary-adrenal axis, autonomic nervous system, and immune system have been proposed to underlie the antidepressant effect of exercise. Using a population sample of 715 adolescents, we examined whether pathways from exercise to affective and somatic symptoms of depression were med

  5. Chronic Psychosocial Factors and Acute Physiological Responses to Laboratory-Induced Stress in Healthy Populations: A Quantitative Review of 30 Years of Investigations

    Science.gov (United States)

    Chida, Yoichi; Hamer, Mark

    2008-01-01

    This meta-analysis included 729 studies from 161 articles investigating how acute stress responsivity (including stress reactivity and recovery of hypothalamic-pituitary-adrenal [HPA] axis, autonomic, and cardiovascular systems) changes with various chronic psychosocial exposures (job stress; general life stress; depression or hopelessness;…

  6. Methylation of the Glucocorticoid Receptor Gene Promoter in Preschoolers: Links with Internalizing Behavior Problems

    Science.gov (United States)

    Parade, Stephanie H.; Ridout, Kathryn K.; Seifer, Ronald; Armstrong, David A.; Marsit, Carmen J.; McWilliams, Melissa A.; Tyrka, Audrey R.

    2016-01-01

    Accumulating evidence suggests that early adversity is linked to methylation of the glucocorticoid receptor (GR) gene, "NR3C1," which is a key regulator of the hypothalamic-pituitary-adrenal axis. Yet no prior work has considered the contribution of methylation of "NR3C1" to emerging behavior problems and psychopathology in…

  7. Stress and Cognition: the relevance of timing, steroid receptors and sex differences

    NARCIS (Netherlands)

    Cornelisse, S.

    2013-01-01

    In response to a stressful situation the autonomic nervous system (ANS) and hypothalamic-pituitary-adrenal (HPA) axis are activated, eventually leading to the release of catecholamines and corticosteroids. These stress hormones bind to different receptors in the brain (in case of corticosteroids, mi

  8. The stress system in the human brain in depression and neurodegeneration.

    NARCIS (Netherlands)

    Swaab, D.F.; Bao, A.-M.; Lucassen, P.J.

    2005-01-01

    Corticotropin-releasing hormone (CRH) plays a central role in the regulation of the hypothalamic-pituitary-adrenal (HPA)-axis, i.e., the final common pathway in the stress response. The action of CRH on ACTH release is strongly potentiated by vasopressin, that is co-produced in increasing amounts wh

  9. The stress system in the human brain in depression and neurodegeneration

    NARCIS (Netherlands)

    Swaab, D.F.; Bao, A.M; Lucassen, P.J.

    2005-01-01

    Corticotropin-releasing hormone (CRH) plays a central role in the regulation of the hypothalamic-pituitary-adrenal (HPA)-axis, i.e., the final common pathway in the stress response. The action of CRH on ACTH release is strongly potentiated by vasopressin, that is co-produced in increasing amounts wh

  10. Associations between circadian and stress response cortisol in children

    NARCIS (Netherlands)

    Simons, S.S.H.; Cillessen, A.H.N.; Weerth, C. de

    2017-01-01

    Hypothalamic-pituitary-adrenal (HPA) axis functioning is characterized by the baseline production of cortisol following a circadian rhythm, as well as by the superimposed production of cortisol in response to a stressor. However, it is relatively unknown whether the basal cortisol circadian rhythm i

  11. Enhanced Cortisol Response to Stress in Children in Autism

    Science.gov (United States)

    Spratt, Eve G.; Nicholas, Joyce S.; Brady, Kathleen T.; Carpenter, Laura A.; Hatcher, Charles R.; Meekins, Kirk A.; Furlanetto, Richard W.; Charles, Jane M.

    2012-01-01

    Children with Autism often show difficulties in adapting to change. Previous studies of cortisol, a neurobiologic stress hormone reflecting hypothalamic-pituitary-adrenal (HPA) axis activity, in children with autism have demonstrated variable results. This study measured cortisol levels in children with and without Autism: (1) at rest; (2) in a…

  12. Classroom Emotional Support Predicts Differences in Preschool Children's Cortisol and Alpha-Amylase Levels

    Science.gov (United States)

    Hatfield, Bridget E.; Hestenes, Linda L.; Kintner-Duffy, Victoria L.; O'Brien, Marion

    2013-01-01

    Accumulating evidence suggests children enrolled in full-time child care often display afternoon elevations of the hormone cortisol, which is an indicator of stress. Recent advances in immunoassays allow for measurement of activity in the hypothalamic-pituitary-adrenal axis and the autonomic sympathetic nervous system from saliva, and measurement…

  13. Breakfast skippers display a disrupted cortisol rhythm and elevated blood pressure

    Science.gov (United States)

    Chronic stress and over-activity in the hypothalamic-pituitary-adrenal (HPA) axis may link breakfast skipping and poor cardiometabolic health. Missing the first major meal of the day in rodents prolongs elevated circulating corticosterone at a time when it’s normally decreasing. To extend these fi...

  14. Early Social Deprivation and the Social Buffering of Cortisol Stress Responses in Late Childhood: An Experimental Study

    Science.gov (United States)

    Hostinar, Camelia E.; Johnson, Anna E.; Gunnar, Megan R.

    2015-01-01

    The goal of the present study was to investigate the role of early social deprivation in shaping the effectiveness of parent support to alleviate hypothalamic-pituitary-adrenal (HPA)-axis-stress responses of children (ages 8.9-11, M = 9.83 years, SD = 0.55). The sample was equally divided between children who had been adopted internationally from…

  15. Having your cake and eating it too: A habit of comfort food may link chronic social stress exposure and acute stress-induced cortisol hyporesponsiveness.

    Science.gov (United States)

    Stress has been tied to changes in eating behavior and food choice. Previous studies in rodents have shown that chronic stress increases palatable food intake which, in turn, increases mesenteric fat and inhibits acute stress-induced hypothalamic-pituitary-adrenal (HPA) axis activity. The effect of...

  16. Stress, Cortisol, and Externalizing Behavior in Adolescent Males: An Examination in the Context of Multisystemic Therapy

    Science.gov (United States)

    Schechter, Julia C.; Brennan, Patricia A.; Cunningham, Phillippe B.; Foster, Sharon L.; Whitmore, Elizabeth

    2012-01-01

    Stress and hypothalamic-pituitary-adrenal (HPA) axis dysregulation have been associated with externalizing behavior in adolescence, but few studies have examined these factors in a treatment context. This study investigated the relationship between stress, cortisol, and externalizing behavior among 120 adolescent males (mean age = 15) receiving…

  17. Daily Cortisol Activity, Loneliness, and Coping Efficacy in Late Adolescence: A Longitudinal Study of the Transition to College

    Science.gov (United States)

    Drake, Emily C.; Sladek, Michael R.; Doane, Leah D.

    2016-01-01

    Many late adolescents who transition to the college environment perceive changes in psychosocial stress. One such stressor, loneliness, has been associated with numerous health problems among adolescents and adults. The hypothalamic-pituitary-adrenal axis is one mechanism through which loneliness may affect health. Guided by a risk and resilience…

  18. Locus of Control Predicts Cortisol Reactivity and Speech Performance in Response to Acute Stress in Undergraduate Students

    Science.gov (United States)

    Szabo, Yvette Z.; Chang, Andrew; Chancellor-Freeland, Cheryl

    2015-01-01

    Previous studies have found that an individual's perception of control in a situation (Locus of Control; LOC) can serve as a protective factor that has physiological and psychological benefits. The present study examines LOC in an acute stress paradigm to examine the relationship between LOC and hypothalamic-pituitary-adrenal axis functioning as…

  19. Glucocorticoid receptor haplotype is associated with a decreased risk of delirium in the elderly

    NARCIS (Netherlands)

    Manenschijn, L; van Rossum, E F C; Jetten, A M; de Rooij, S E; van Munster, B C

    2011-01-01

    Delirium is the most common mental disorder at older age in hospitals after acute admission. The pathogenesis of delirium is largely unknown. Hyperactivity of the hypothalamic-pituitary-adrenal axis, leading to increased cortisol levels, has been suggested to play a role in the development of deliri

  20. In abstinent MDMA users the cortisol awakening response is off-set but associated with prefrontal serotonin transporter binding as in non-users

    DEFF Research Database (Denmark)

    Frokjaer, Vibe Gedsoe; Erritzoe, David; Holst, Klaus Kähler

    2014-01-01

    Serotonergic signaling is considered critical for an appropriate adaptation to stress. We have previously observed that in healthy volunteers, prefrontal serotonin transporter (SERT) binding is positively associated with hypothalamic-pituitary-adrenal (HPA)-axis output in terms of the cortisol...

  1. Influence of fetal growth velocity and smallness at birth on adrenal function in adolescence

    DEFF Research Database (Denmark)

    Beck Jensen, Rikke; vielwerth, Signe; Larsen, Torben;

    2011-01-01

    The hypothalamic-pituitary-adrenal axis is susceptible to programming during fetal development and may be linked to risk of disease later in life. In a former prospective study the cohort was divided into those born appropriate for gestational age (AGA) or small for gestational age (SGA; birth...

  2. Off-Time Pubertal Timing Predicts Physiological Reactivity to Postpuberty Interpersonal Stress

    Science.gov (United States)

    Smith, Anne Emilie; Powers, Sally I.

    2009-01-01

    We investigated associations between retrospectively assessed timing of pubertal development, interpersonal interactions, and hypothalamic-pituitary-adrenal axis reactivity to an interpersonal stress task in 110 young adult women. Participants provided salivary cortisol samples at points prior and subsequent to a video-taped conflict discussion…

  3. Children with asthma have significantly lower long-term cortisol levels in their scalp hair than healthy children

    NARCIS (Netherlands)

    Kamps, Arvid W. A.; Molenmaker, Marco; Kemperman, Ramses; van der Veen, Betty S.; Bocca, Gianni; Veeger, Nic J. G. M.

    Aim: Noninvasive measurement of long-term cortisol levels is a useful way of evaluating the effect of chronic disease on the hypothalamic-pituitary-adrenal axis in children. The aim of this pilot study was to compare hair cortisol levels in children using inhaled corticosteroids for asthma and

  4. Treating infants for umbilical granuloma with topical clobetasol propionate cream

    DEFF Research Database (Denmark)

    Brødsgaard, Anne; Nielsen, Tove; Mølgaard, Ulla

    2015-01-01

    , such as suppression of the hypothalamic-pituitary-adrenal axis, as we did not investigate this. However, the risk of meaningful systemic side effects may be considered negligible, as only a small amount of cream, of between 2-5 mg per application, was applied to a very small surface area. This article is protected...

  5. Salivary Cortisol Levels in Persons With and Without Different Anxiety Disorders

    NARCIS (Netherlands)

    Vreeburg, Sophie A.; Zitman, Frans G.; van Pelt, Johannes; DeRijk, Roel H.; Verhagen, Jolanda C. M.; van Dyck, Richard; Hoogendijk, Witte J. G.; Smit, Johannes H.; Penninx, Brenda

    2010-01-01

    Objective: To examine the association between several subtypes of anxiety disorders and various cortisol indicators in a large cohort study. Anxiety disorders have been suggested to be linked to hypothalamic-pituitary-adrenal (HPA) axis activity, although results are scarce and inconsistent. No earl

  6. Glucocorticoid receptor gene haplotypes are not associated with birth anthropometry, blood pressure, glucose and insulin concentrations, and body composition in subjects born small for gestational age

    NARCIS (Netherlands)

    L. Manenschijn (Laura); E.L.T. van den Akker (Erica); W.A. Ester (Wietske); R.W.J. Leunissen (Ralph); R.H. Willemsen (Ruben); E.F.C. van Rossum (Liesbeth); J.W. Koper (Jan); S.W.J. Lamberts (Steven); A.C.S. Hokken-Koelega (Anita)

    2010-01-01

    textabstractObjective: Smaller size at birth has been associated with an increased risk of metabolic and cardiovascular disorders in adult life. Fetal programing of the hypothalamic - pituitary - adrenal axis has been suggested as a possible explanation. Fetal glucocorticoid (GC) overexposure has ef

  7. The relationships of working conditions, recent stressors and childhood trauma with salivary cortisol levels

    NARCIS (Netherlands)

    Holleman, Michiel; Vreeburg, Sophie A.; Dekker, Jack J. M.; Penninx, Brenda W. J. H.

    2012-01-01

    Background: An etiological model has been suggested where stress leads to high cortisol levels and hypothalamic-pituitary-adrenal (HPA) axis dysregulation, resulting in somatic diseases and psychopathology. To evaluate this model we examined the association of different stressors (working conditions

  8. Decision-making under risk and ambiguity in low-birth-weight pigs

    NARCIS (Netherlands)

    Murphy, Eimear; Kraak, Lynn; van den Broek, Jan; Nordquist, Rebecca E; van der Staay, Franz Josef

    2015-01-01

    Low birth weight (LBW) in humans is a risk factor for later cognitive, behavioural and emotional problems. In pigs, LBW is associated with higher mortality, but little is known about consequences for surviving piglets. Alteration in hypothalamic-pituitary-adrenal axis function in LBW pigs suggests a

  9. Physiological and endocrine reactions to psychosocial stress in alcohol use disorders: duration of abstinence matters

    NARCIS (Netherlands)

    Starcke, K.; Holst, R.J. van; Brink, W. van den; Veltman, D.J.; Goudriaan, A.E.

    2013-01-01

    BACKGROUND: Recent research findings suggest that heavy alcohol use is associated with alterations of the hypothalamic-pituitary-adrenal axis and autonomic nervous system function and that early abstinence is associated with blunted stress responsiveness. METHODS: This study investigated abstinent a

  10. Classroom Emotional Support Predicts Differences in Preschool Children's Cortisol and Alpha-Amylase Levels

    Science.gov (United States)

    Hatfield, Bridget E.; Hestenes, Linda L.; Kintner-Duffy, Victoria L.; O'Brien, Marion

    2013-01-01

    Accumulating evidence suggests children enrolled in full-time child care often display afternoon elevations of the hormone cortisol, which is an indicator of stress. Recent advances in immunoassays allow for measurement of activity in the hypothalamic-pituitary-adrenal axis and the autonomic sympathetic nervous system from saliva, and measurement…

  11. Peer Victimization and Aggression: Moderation by Individual Differences in Salivary Cortisol and Alpha-Amylase

    Science.gov (United States)

    Rudolph, Karen D.; Troop-Gordon, Wendy; Granger, Douglas A.

    2010-01-01

    This research examined whether variations in salivary measures of the hypothalamic-pituitary-adrenal axis (cortisol) and autonomic nervous system (alpha amylase [sAA]) contribute to individual differences in the association between peer victimization and aggression. Children (N = 132; M age = 9.46 years, SD = 0.33) completed a measure of peer…

  12. Investigations of HPA Function and the Enduring Consequences of Stressors in Adolescence in Animal Models

    Science.gov (United States)

    McCormick, Cheryl M.; Mathews, Iva Z.; Thomas, Catherine; Waters, Patti

    2010-01-01

    Developmental differences in hypothalamic-pituitary-adrenal (HPA) axis responsiveness to stressors and ongoing development of glucocorticoid-sensitive brain regions in adolescence suggest that similar to the neonatal period of ontogeny, adolescence may also be a sensitive period for programming effects of stressors on the central nervous system.…

  13. Salivary cortisol and binge eating disorder in obese women after surgery for morbid obesity

    NARCIS (Netherlands)

    Larsen, J.K.; Ramshorst, B. van; Doornen, L.J.P. van; Geenen, R.

    2009-01-01

    Background Binge eating episodes characterized by loss of control are hypothesized to be accompanied by changes in hypothalamic pituitary adrenal (HPA) axis functioning. Cortisol is an end product of this neuroendocrine stress system. Purpose The aim of this study was to examine the cortisol leve

  14. Separation of pair housed roosters is associated with transient increased corticosteroid excretion

    DEFF Research Database (Denmark)

    Hau, Jann; Carlsson, H E; Royo, F

    2009-01-01

    the second day after separation indicating that the separation and relocation is associated with an activation of the hypothalamic-pituitary-adrenal axis. The excretion of ICCM in droppings was not correlated to the concentration of ICCM in droppings. It is thus important that excretion of ICCM be expressed...

  15. Salivary Cortisol Levels in Persons With and Without Different Anxiety Disorders

    NARCIS (Netherlands)

    Vreeburg, Sophie A.; Zitman, Frans G.; van Pelt, Johannes; DeRijk, Roel H.; Verhagen, Jolanda C. M.; van Dyck, Richard; Hoogendijk, Witte J. G.; Smit, Johannes H.; Penninx, Brenda

    2010-01-01

    Objective: To examine the association between several subtypes of anxiety disorders and various cortisol indicators in a large cohort study. Anxiety disorders have been suggested to be linked to hypothalamic-pituitary-adrenal (HPA) axis activity, although results are scarce and inconsistent. No earl

  16. The effect of depressive symptomatology on plasma cortisol responses to acute bicycle exercise among post-menopausal women

    NARCIS (Netherlands)

    van der Pompe, G.; Bernards, N; Meijman, T.F.; Heijnen, C.J

    1999-01-01

    The present study was designed to elucidate the effect of depressive symptomatology on the cortisol response to strenuous exercise. Thirteen healthy, post-menopausal women participated in this study. The results show that acute bicycle exercise activates the hypothalamic-pituitary-adrenal (HPA) axis

  17. The role of hypocortisolism in chronic fatigue syndrome

    NARCIS (Netherlands)

    Nijhof, S.L.; Rutten, J.M.; Uiterwaal, C.S.; Bleijenberg, G.; Kimpen, J.L.L.; Putte, E.M. van de

    2014-01-01

    BACKGROUND: There is accumulating evidence of hypothalamic-pituitary-adrenal (HPA) axis hypofunction in chronic fatigue syndrome (CFS). However, knowledge of this hypofunction has so far come exclusively from research in adulthood, and its clinical significance remains unclear. The objective of the

  18. New insights into the controversy of adrenal function during critical illness.

    Science.gov (United States)

    Boonen, Eva; Bornstein, Stefan R; Van den Berghe, Greet

    2015-10-01

    Critical illness represents a life-threatening disorder necessitating recruitment of defence mechanisms for survival. Herein, the hypothalamic-pituitary-adrenal axis is essential. However, the relevance of a relative insufficiency of the hypothalamic-pituitary-adrenal axis in critical illness, which is diagnosed by a suppressed cortisol response to exogenous adrenocorticotropic hormone (ACTH) irrespective of the plasma cortisol concentration, is controversial. Findings from several studies have provided insights that clarify at least part of this controversy. Rather than an activated hypothalamic-pituitary-adrenal axis, ACTH-independent regulators have been reported to contribute to increased cortisol availability during critical illness. One of these regulators is reduced cortisol breakdown, mediated by suppressed expression and activity of cortisol metabolising enzymes in the liver and kidneys. This downstream mechanism increases concentrations of plasma cortisol, but the ensuing feedback-inhibited ACTH release, when sustained for more than 1 week, has been shown to negatively affect adrenocortical integrity and function. Reduced adrenocortical ACTH signalling could explain reduced cortisol responses to exogenous ACTH. Whether such reduced cortisol responses in the presence of raised plasma (free) cortisol identifies adrenal failure needing treatment is unlikely. Additionally, reduced cortisol breakdown affects the optimum dose of hydrocortisone treatment during critical illness. Identification of patients with an insufficient hypothalamic-pituitary-adrenal axis response and the optimum treatment for this disorder clearly need more well designed preclinical and clinical studies.

  19. Long-term stability of salivary cortisol

    DEFF Research Database (Denmark)

    Garde, A H; Hansen, Åse Marie

    2005-01-01

    The measurement of salivary cortisol provides a simple, non-invasive, and stress-free measure frequently used in studies of the hypothalamic-pituitary-adrenal axis activity. In research projects, samples are often required to be stored for longer periods of time either because of the protocol of ...

  20. Pituitary gland volume in patients with schizophrenia, subjects at ultra high-risk of developing psychosis and healthy controls

    DEFF Research Database (Denmark)

    Nordholm, Dorte; Krogh, Jesper; Mondelli, Valeria;

    2013-01-01

    A larger pituitary size is thought to reflect a greater activation of the hypothalamic-pituitary-adrenal (HPA) axis, which may be related to an increase in the number and size of corticotroph cells. Some studies, but not all, indicate that pituitary volume increases before or at the onset...

  1. The Moderating Role of Sensory Overresponsivity in HPA Activity: A Pilot Study with Children Diagnosed with ADHD

    Science.gov (United States)

    Reynolds, Stacey; Lane, Shelly J.; Gennings, Chris

    2010-01-01

    Objective: To determine if sensory overresponsivity (SOR) is a moderating condition impacting the activity of the Hypothalamic Pituitary Adrenal (HPA) Axis in children with ADHD. Method: Participants were children with (n = 24) and without ADHD (n = 24). Children in the ADHD group were divided into SOR (ADHDs) and non-SOR (ADHDt) groups using the…

  2. Locus of Control Predicts Cortisol Reactivity and Speech Performance in Response to Acute Stress in Undergraduate Students

    Science.gov (United States)

    Szabo, Yvette Z.; Chang, Andrew; Chancellor-Freeland, Cheryl

    2015-01-01

    Previous studies have found that an individual's perception of control in a situation (Locus of Control; LOC) can serve as a protective factor that has physiological and psychological benefits. The present study examines LOC in an acute stress paradigm to examine the relationship between LOC and hypothalamic-pituitary-adrenal axis functioning as…

  3. Stress, Cortisol, and Externalizing Behavior in Adolescent Males: An Examination in the Context of Multisystemic Therapy

    Science.gov (United States)

    Schechter, Julia C.; Brennan, Patricia A.; Cunningham, Phillippe B.; Foster, Sharon L.; Whitmore, Elizabeth

    2012-01-01

    Stress and hypothalamic-pituitary-adrenal (HPA) axis dysregulation have been associated with externalizing behavior in adolescence, but few studies have examined these factors in a treatment context. This study investigated the relationship between stress, cortisol, and externalizing behavior among 120 adolescent males (mean age = 15) receiving…

  4. Enhanced Cortisol Response to Stress in Children in Autism

    Science.gov (United States)

    Spratt, Eve G.; Nicholas, Joyce S.; Brady, Kathleen T.; Carpenter, Laura A.; Hatcher, Charles R.; Meekins, Kirk A.; Furlanetto, Richard W.; Charles, Jane M.

    2012-01-01

    Children with Autism often show difficulties in adapting to change. Previous studies of cortisol, a neurobiologic stress hormone reflecting hypothalamic-pituitary-adrenal (HPA) axis activity, in children with autism have demonstrated variable results. This study measured cortisol levels in children with and without Autism: (1) at rest; (2) in a…

  5. Glucocorticoid pulsatility : implications for brain functioning

    NARCIS (Netherlands)

    Sarabdjitsingh, Ratna Angela

    2010-01-01

    Pronounced ultradian and circadian rhythms in the hormones of the hypothalamic-pituitary-adrenal (HPA) axis (i.e. glucocorticoids), one of the body’s major neuroendocrine axes, were already demonstrated several decades ago. Until now, the clinical relevance of the pulsatile nature of glucocorticoids

  6. The stress system in the human brain in depression and neurodegeneration.

    NARCIS (Netherlands)

    Swaab, D.F.; Bao, A.-M.; Lucassen, P.J.

    2005-01-01

    Corticotropin-releasing hormone (CRH) plays a central role in the regulation of the hypothalamic-pituitary-adrenal (HPA)-axis, i.e., the final common pathway in the stress response. The action of CRH on ACTH release is strongly potentiated by vasopressin, that is co-produced in increasing amounts wh

  7. The stress system in the human brain in depression and neurodegeneration

    NARCIS (Netherlands)

    Swaab, D.F.; Bao, A.M; Lucassen, P.J.

    2005-01-01

    Corticotropin-releasing hormone (CRH) plays a central role in the regulation of the hypothalamic-pituitary-adrenal (HPA)-axis, i.e., the final common pathway in the stress response. The action of CRH on ACTH release is strongly potentiated by vasopressin, that is co-produced in increasing amounts wh

  8. Der er sammenhæng mellem posttraumatisk belastningsreaktion og irritabel tyktarm

    DEFF Research Database (Denmark)

    Wernersson, Rebecca; Carlsson, Jessica

    2014-01-01

    and posttraumatic stress disorder (PTSD). There are several hypotheses of how this association can be explained, e.g. oxytocin dysregulation, hypothalamic-pituitary-adrenal axis dysfunction, the vulnerability of the patient group, post-infectious irritable bowel and side effects of the medical treatment of PTSD....

  9. Salivary cortisol and binge eating disorder in obese women after surgery for morbid obesity

    NARCIS (Netherlands)

    Larsen, J.K.; Ramshorst, B. van; Doornen, L.J.P. van; Geenen, R.

    2009-01-01

    Background Binge eating episodes characterized by loss of control are hypothesized to be accompanied by changes in hypothalamic pituitary adrenal (HPA) axis functioning. Cortisol is an end product of this neuroendocrine stress system. Purpose The aim of this study was to examine the cortisol

  10. Cortisol response to critical illness: Effect of intensive insulin therapy

    NARCIS (Netherlands)

    I. Vanhorebeek (Ilse); R.P. Peeters (Robin); S.V. Perre (Sarah Vander); I. Jans (Ivo); P.J. Wouters (Pieter); K. Skogstrand (Kristin); T.K. Hansen (Troels); R. Bouillon (Roger); G. van den Berghe (Greet)

    2006-01-01

    textabstractContext: Both excessive and insufficient activation of the hypothalamic-pituitary-adrenal axis in response to critical illness is associated with increased mortality. Objective: The objective of the study was to study the effect of intensive insulin therapy, recently shown to reduce mort

  11. Markers of stress and inflammation as potential mediators of the relationship between exercise and depressive symptoms : Findings from the TRAILS study

    NARCIS (Netherlands)

    Booij, Sanne H; Bos, Elisabeth H; de Jonge, Peter; Oldehinkel, Albertine J

    The hypothalamic-pituitary-adrenal axis, autonomic nervous system, and immune system have been proposed to underlie the antidepressant effect of exercise. Using a population sample of 715 adolescents, we examined whether pathways from exercise to affective and somatic symptoms of depression were

  12. "More than skin deep": stress neurobiology and mental health consequences of racial discrimination.

    Science.gov (United States)

    Berger, Maximus; Sarnyai, Zoltán

    2015-01-01

    Ethnic minority groups across the world face a complex set of adverse social and psychological challenges linked to their minority status, often involving racial discrimination. Racial discrimination is increasingly recognized as an important contributing factor to health disparities among non-dominant ethnic minorities. A growing body of literature has recognized these health disparities and has investigated the relationship between racial discrimination and poor health outcomes. Chronically elevated cortisol levels and a dysregulated hypothalamic-pituitary-adrenal (HPA) axis appear to mediate effects of racial discrimination on allostatic load and disease. Racial discrimination seems to converge on the anterior cingulate cortex (ACC) and may impair the function of the prefrontal cortex (PFC), hence showing substantial similarities to chronic social stress. This review provides a summary of recent literature on hormonal and neural effects of racial discrimination and a synthesis of potential neurobiological pathways by which discrimination affects mental health.

  13. Subclinical Cushing's syndrome due to unilateral or bilateral adrenal incidentalomas. Problems of diagnostic and indication to surgical treatment. Review of literature

    Directory of Open Access Journals (Sweden)

    Nikolay Sergeevich Kuznetsov

    2015-05-01

    Full Text Available Today subclinical Cushing's syndrome is the most widespread variant of hormonal activity of incidentaloma's hormonal activity. This pathology is defined as a mild intensity autonomous cortisol hypersecretion, not causing specific clinical signs of hypercorticism, but detectable biochemically as derangements of the hypothalamic-pituitary-adrenal axis function. Some clinical symptomatology of metabolic syndrome, such as obesity, impaired carbohydrate metabolism and hypertension, are peculiar to subclinical hypercorticism more than to population. As a result all these symptomatology could lead to increasing cardiovascular risk. Till now there isn't a definite opinion about the need of surgical treatment of present pathology. But there is evidence, that after removing of incidentalomas clinical symptomatology of metabolic syndrome are improving. For understanding all possible risks, connected with subclinical hypercorticism, it's necessary to study the origins of their arising and present about the most adequate screening tests. 

  14. Chronic stress induces structural alterations in splenic lymphoid tissue that are associated with changes in corticosterone levels in wistar-kyoto rats.

    Science.gov (United States)

    Hernandez, María Eugenia; Martinez-Mota, Lucia; Salinas, Citlaltepetl; Marquez-Velasco, Ricardo; Hernandez-Chan, Nancy G; Morales-Montor, Jorge; Pérez-Tapia, Mayra; Streber, María L; Granados-Camacho, Ivonne; Becerril, Enrique; Javier, Baquera-Heredia; Pavón, Lenin

    2013-01-01

    Major depressive disorder patients present chronic stress and decreased immunity. The Wistar-Kyoto rat (WKY) is a strain in which the hypothalamic-pituitary-adrenal axis is overactivated. To determine whether chronic stress induces changes in corticosterone levels and splenic lymphoid tissue, 9-week-old male rats were subject to restraint stress (3 h daily), chemical stress (hydrocortisone treatment, 50 mg/Kg weight), mixed stress (restraint plus hydrocortisone), or control treatment (without stress) for 1, 4, and 7 weeks. The serum corticosterone levels by RIA and spleens morphology were analyzed. Corticosterone levels as did the structure, size of the follicles and morphology of the parenchyma (increase in red pulp) in the spleen, varied depending on time and type of stressor. These changes indicate that chronic stress alters the immune response in the spleen in WKY rats by inducing morphological changes, explaining in part the impaired immunity that develops in organisms that are exposed to chronic stress.

  15. Hormones, stress, and cognition: The effects of glucocorticoids and oxytocin on memory

    Science.gov (United States)

    Wirth, Michelle M.

    2014-01-01

    Hormones have nuanced effects on learning and memory processes. The degree and direction of the effect (e.g., is memory impaired or enhanced?) depends on the dose, type and stage of memory, and type of material being learned, among other factors. This review will focus on two specific topics within the realm of effects of hormones on memory: (1) How glucocorticoids (the output hormones of the hypothalamic-pituitary-adrenal axis) affect long-term memory consolidation, retrieval, and working memory, with a focus on neural mechanisms and effects of emotion; and (2) How oxytocin affects memory, with emphasis on a speculative hypothesis that oxytocin might exert its myriad effects on human social cognition and behavior via impacts on more general cognitive processes. Oxytocin-glucocorticoid interactions will be briefly addressed. These effects of hormones on memory will also be considered from an evolutionary perspective. PMID:25893159

  16. Intracerebroventricular injection of leukotriene B4 attenuates antigen-induced asthmatic response via BLT1 receptor stimulating HPA-axis in sensitized rats

    Directory of Open Access Journals (Sweden)

    Jiang Jun-Xia

    2010-04-01

    Full Text Available Abstract Background Basic and clinical studies suggest that hypothalamic-pituitary-adrenal (HPA axis is the neuroendocrine-immnue pathway that functionally regulates the chronic inflammatory disease including asthma. Our previous studies showed corresponding changes of cytokines and leukotriene B4 (LTB4 between brain and lung tissues in antigen-challenged asthmatic rats. Here, we investigated how the increased LTB4 level in brain interacts with HPA axis in regulating antigen-induced asthmatic response in sensitized rats. Methods Ovalbumin-sensitized rats were challenged by inhalation of antigen. Rats received vehicle, LTB4 or U75302 (a selective LTB4 BLT1 receptor inhibitor was given via intracerebroventricular injection (i.c.v 30 min before challenge. Lung resistance (RL and dynamic lung compliance (Cdyn were measured before and after antigen challenge. Inflammatory response in lung tissue was assessed 24 h after challenge. Expression of CRH mRNA and protein in hypothalamus were evaluated by RT-PCR and Western Blot, and plasma levels of adrenocorticotropic hormone (ACTH and corticosterone (CORT were measured using the ELISA kits. Results Antigen challenge decreased pulmonary function and induced airway inflammation, evoked HPA axis response in sensitized rats. Administration of LTB4 via i.c.v markedly attenuated airway contraction and inflammation. Meanwhile, LTB4 via i.c.v markedly increased CORT and ACTH level in plasma before antigen challenge, and followed by further increases in CORT and ACTH levels in plasma after antigen challenge in sensitized rats. Expression of CRH mRNA and protein in hypothalamus were also significantly increased by LTB4 via i.c.v in sensitized rats after antigen challenge. These effect were completely blocked by pre-treatment with BLT1 receptor antagonist U75302 (10 ng, but not by BLT2 antagonist LY255283. Conclusions LTB4 administered via i.c.v down-regulates the airway contraction response and inflammation through

  17. Hypopituitarism in the elderly: a narrative review on clinical management of hypothalamic-pituitary-gonadal, hypothalamic-pituitary-thyroid and hypothalamic-pituitary-adrenal axes dysfunction.

    Science.gov (United States)

    Curtò, L; Trimarchi, F

    2016-10-01

    Hypopituitarism is an uncommon and under-investigated endocrine disorder in old age since signs and symptoms are unspecific and, at least in part, can be attributed to the physiological effects of aging and related co-morbidities. Clinical presentation is often insidious being characterized by non-specific manifestations, such as weight gain, fatigue, low muscle strength, bradipsychism, hypotension or intolerance to cold. In these circumstances, hypopituitarism is a rarely life-threatening condition, but evolution may be more dramatic as a result of pituitary apoplexy, or when a serious condition of adrenal insufficiency suddenly occurs. Clinical presentation depends on the effects that each pituitary deficit can cause, and on their mutual relationship, but also, inevitably, it depends on the severity and duration of the deficit itself, as well as on the general condition of the patient. Indeed, indications and methods of hormone replacement therapy must include the need to normalize the endocrine profile without contributing to the worsening of intercurrent diseases, such as those of glucose and bone metabolism, and the cardiovascular system, or to the increasing cancer risk. Hormonal requirements of elderly patients are reduced compared to young adults, but a prompt diagnosis and appropriate treatment of pituitary deficiencies are strongly recommended, also in this age range.

  18. Subclinical Cushing's syndrome: current concepts and trends.

    Science.gov (United States)

    Zografos, George N; Perysinakis, Iraklis; Vassilatou, Evangeline

    2014-01-01

    Clinically inapparent adrenal masses which are incidentally detected have become a common problem in everyday practice. Approximately 5-20% of adrenal incidentalomas present subclinical cortisol hypersecretion which is characterized by subtle alterations of the hypothalamic-pituitary-adrenal axis due to adrenal autonomy. This disorder has been described as subclinical Cushing's syndrome, since there is no typical clinical phenotype. The diagnosis of subclinical Cushing's syndrome is based on biochemical evaluation; however, there is still no consensus for the biochemical diagnostic criteria. An abnormal 1mg dexamethasone suppression test (DST) as initial screening test in combination with at least one other abnormal test of the hypothalamic-pituitary-adrenal axis has been advocated by most experts for the diagnosis of subclinical Cushing's syndrome. DST is the main method of establishing the diagnosis, while there is inhomogeneity of the information that other tests provide. Arterial hypertension, diabetes mellitus type 2 or impaired glucose tolerance, central obesity, osteoporosis/vertebral fractures and dyslipidemia are considered as detrimental effects of chronic subtle cortisol excess, although there is no proven causal relationship between subclinical cortisol hypersecretion and these morbidities. Therapeutic strategies include careful observation along with medical treatment of morbidities potentially related to subtle cortisol hypersecretion versus laparoscopic adrenalectomy. The optimal management of patients with subclinical Cushing's syndrome is not yet defined. The conservative approach is appropriate for the majority of these patients; however, the duration of follow-up and the frequency of periodical evaluation still remain open issues. Surgical resection may be beneficial for patients with hypertension, diabetes mellitus type 2 or abnormal glucose tolerance and obesity.

  19. The role of oestradiol in sexually dimorphic hypothalamic-pituitary-adrena axis responses to intracerebroventricular ethanol administration in the rat.

    Science.gov (United States)

    Larkin, J W; Binks, S L; Li, Y; Selvage, D

    2010-01-01

    Systemic ethanol (EtOH) administration activates the hypothalamic-pituitary-adrenal (HPA) axis of rats in a sexually dimorphic manner. The present studies tested the role played by the central nervous system (CNS) in this phenomenon. To localise the effects of the drug to the brain, we utilised an experimental paradigm whereby a small, nontoxic amount of the drug was delivered via intracerebroventricular (i.c.v.) injection. EtoH administered i.c.v. rapidly diffuses throughout the cerebrospinal fluid and brain, and does not cause neuronal damage or have any long-term physiological or behavioural effects. Experimental groups included intact males, intact cycling females, and ovariectomised (OVX) animals with or without replacement oestradiol (E(2)). Intracerebroventricular EtOH-induced HPA hormonal activation was determined by measuring plasma adrenocorticotrophin (ACTH) levels. Activation of brain areas that both regulate HPA function and are responsive to gonadal hormones was determined using expression of the transcription factor c-fos (Fos) as a marker of neuronal activity. We observed sex- and oestrous cycle- dependent differences in HPA activation by EtOH as measured by both these parameters. ACTH secretion was highest in females in pro-oestrus or oestrus, just prior to or after the endogenous peak of E(2), as was Fos expression in the paraventricular nucleus of the hypothalamus (PVN) and the locus coreuleus (LC) of the brainstem. In OVX animals, E(2) replacement caused an increase in PVN and LC Fos expression in response to i.c.v. EtOH compared to OVX controls, but a decrease in ACTH secretion. Taken together, these results indicate that at the level of the CNS, EtOH stimulates HPA activity more robustly at times when the effects of E(2) are high, but that E(2) alone is not responsible for this effect. The data further suggest that the LC plays an important role in the circuitry, which appears to be different from that activated following the systemic

  20. Impaired Sympathoadrenal Axis Function Contributes to Enhanced Insulin Secretion in Prediabetic Obese Rats

    Directory of Open Access Journals (Sweden)

    Ana Eliza Andreazzi

    2011-01-01

    Full Text Available The involvement of sympathoadrenal axis activity in obesity onset was investigated using the experimental model of treating neonatal rats with monosodium L-glutamate. To access general sympathetic nervous system activity, we recorded the firing rates of sympathetic superior cervical ganglion nerves in animals. Catecholamine content and secretion from isolated adrenal medulla were measured. Intravenous glucose tolerance test was performed, and isolated pancreatic islets were stimulated with glucose and adrenergic agonists. The nerve firing rate of obese rats was decreased compared to the rate for lean rats. Basal catecholamine secretion decreased whereas catecholamine secretion induced by carbachol, elevated extracellular potassium, and caffeine in the isolated adrenal medulla were all increased in obese rats compared to control. Both glucose intolerance and hyperinsulinaemia were observed in obese rats. Adrenaline strongly inhibited glucose-induced insulin secretion in obese animals. These findings suggest that low sympathoadrenal activity contributes to impaired glycaemic control in prediabetic obese rats.

  1. CD36/Sirtuin 1 Axis Impairment Contributes to Hepatic Steatosis in ACE2-Deficient Mice

    Science.gov (United States)

    Qadri, Fatimunnisa; Penninger, Josef M.; Santos, Robson Augusto S.; Bader, Michael

    2016-01-01

    Background and Aims. Angiotensin converting enzyme 2 (ACE2) is an important component of the renin-angiotensin system. Since angiotensin peptides have been shown to be involved in hepatic steatosis, we aimed to evaluate the hepatic lipid profile in ACE2-deficient (ACE2−/y) mice. Methods. Male C57BL/6 and ACE2−/y mice were analyzed at the age of 3 and 6 months for alterations in the lipid profiles of plasma, faeces, and liver and for hepatic steatosis. Results. ACE2−/y mice showed lower body weight and white adipose tissue at all ages investigated. Moreover, these mice had lower levels of cholesterol, triglycerides, and nonesterified fatty acids in plasma. Strikingly, ACE2−/y mice showed high deposition of lipids in the liver. Expression of CD36, a protein involved in the uptake of triglycerides in liver, was increased in ACE2−/y mice. Concurrently, these mice exhibited an increase in hepatic oxidative stress, evidenced by increased lipid peroxidation and expression of uncoupling protein 2, and downregulation of sirtuin 1. ACE2−/y mice also showed impairments in glucose metabolism and insulin signaling in the liver. Conclusions. Deletion of ACE2 causes CD36/sirtuin 1 axis impairment and thereby interferes with lipid homeostasis, leading to lipodystrophy and steatosis. PMID:28101297

  2. Impaired adrenergic- and corticotropic-axis outflow during exercise in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Iranmanesh, Ali; Rochester, Dudley F; Liu, Jing; Veldhuis, Johannes D

    2011-11-01

    Exercise stimulates coordinated release of the sympathoadrenal hormones adrenocorticotropic hormone (ACTH), cortisol, norepinephrine (NE), and epinephrine (Epi). The study hypothesis was that chronic obstructive pulmonary disease (COPD) is marked by heightened sympathoadrenal outflow at comparable relative workloads. The location of the study was at a clinical research unit. Eight healthy men and 9 men with stable COPD (forced expiratory volume at 1 second exercised at individual submaximal (35% ± 5%) or maximal oxygen consumption. Blood was sampled every 2 minutes for 40 minutes concurrently. Two-way analysis of covariance was applied to examine group (healthy/COPD) and exercise (3 levels) effects on ACTH, cortisol, NE, and Epi release and regularity (estimable by approximate entropy). The timing of peak hormone concentrations was Epi, 14 minutes; NE, 16 minutes; ACTH, 22 minutes; and cortisol, 34 minutes in both cohorts. Type of exercise regimen influenced all 4 hormones (each P COPD) affected cortisol (P Exercise regimen and group together controlled ACTH, cortisol, and Epi (each P COPD compared with control subjects. Approximate entropy analysis also identified loss of maximal exercise-induced ACTH-secretory regularity in COPD patients (P = .042). These outcomes demonstrate impaired rather than augmented exercise-associated sympathocorticotropic-axis outflow in patients with COPD even when outcomes are normalized to maximal oxygen consumption, suggesting that factors other than fitness are at work.

  3. Physiological Basis for the Etiology, Diagnosis, and Treatment of Adrenal Disorders: Cushing’s Syndrome, Adrenal Insufficiency, and Congenital Adrenal Hyperplasia

    OpenAIRE

    Raff, Hershel; Sharma, Susmeeta T.; Nieman, Lynnette K.

    2014-01-01

    The hypothalamic-pituitary-adrenal (HPA) axis is a classic neuroendocrine system. One of the best ways to understand the HPA axis is to appreciate its dynamics in the variety of diseases and syndromes that affect it. Excess glucocorticoid activity can be due to endogenous cortisol overproduction (spontaneous Cushing’s syndrome) or exogenous glucocorticoid therapy (iatrogenic Cushing’s syndrome). Endogenous Cushing’s syndrome can be subdivided into ACTH-dependent and ACTH-independent, the latt...

  4. Endocannabinoids and the Endocrine System in Health and Disease.

    Science.gov (United States)

    Hillard, Cecilia J

    2015-01-01

    Some of the earliest reports of the effects of cannabis consumption on humans were related to endocrine system changes. In this review, the effects of cannabinoids and the role of the CB1 cannabinoid receptor in the regulation of the following endocrine systems are discussed: the hypothalamic-pituitary-gonadal axis, prolactin and oxytocin, thyroid hormone and growth hormone, and the hypothalamic-pituitary-adrenal axis. Preclinical and human study results are presented.

  5. Effect of Heavy Ion Brain Radiation on Nerve-immune System Regulation Mechanism in Rat

    Institute of Scientific and Technical Information of China (English)

    YU; Ying-qi; WANG; Xiao; KONG; Fu-quan; SUI; Li; LEI; Run-hong; MA; Hong; DENG; Yu-lin; LI; Qiang

    2013-01-01

    High-dose ionizing irradiation can cause extensive injuries in susceptible tissues.Blood,nervous and immune systems are highly radiation-sensitive.While the nerve-immune system regulation of radiationdamage in the relevant research is rare.So the brain injury model that rats were subjected to 15 Gy of head irradiation was built.By detecting hypothalamic-pituitary-adrenal axis(HPA axis)changes,the

  6. Social Stress and the Reactivation of Latent Herpes Simplex Virus Type 1

    Science.gov (United States)

    Padgett, David A.; Sheridan, John F.; Dorne, Julianne; Berntson, Gary G.; Candelora, Jessica; Glaser, Ronald

    1998-06-01

    Psychological stress is thought to contribute to reactivation of latent herpes simplex virus (HSV). Although several animal models have been developed in an effort to reproduce different pathogenic aspects of HSV keratitis or labialis, until now, no good animal model existed in which application of a psychological laboratory stressor results in reliable reactivation of the virus. Reported herein, disruption of the social hierarchy within colonies of mice increased aggression among cohorts, activated the hypothalamic-pituitary-adrenal axis, and caused reactivation of latent HSV type 1 in greater than 40% of latently infected animals. However, activation of the hypothalamic-pituitary-adrenal axis using restraint stress did not activate the latent virus. Thus, the use of social stress in mice provides a good model in which to investigate the neuroendocrine mechanisms that underlie behaviorally mediated reactivation of latent herpes-viruses.

  7. Normal sweat secretion despite impaired growth hormone-insulin-like growth factor-I axis in obese subjects

    DEFF Research Database (Denmark)

    Rasmussen, M H; Juul, Anders; Main, Katharina M;

    2011-01-01

    Adults with GH deficiency are known to exhibit reduced sweating. Whether sweating capacity is impacted in obese subjects with impaired GH secretion have not previously been investigated. The main objective was to investigate sweat secretion rate and the GH-IGF-I axis in obese subjects before......, and impaired insulin sensitivity, which all were normalised after diet-induced weight loss of 30 ± 5 kg. Sweat secretion rates were similar comparing obese and nonobese subjects (78 ± 10 versus 82 ± 9 mg/30 minutes) and sweat secretion did not change after a diet-induced weight loss in obese subjects. We...... conclude that although obese subjects have markedly reduced GH release and impaired IGF-I levels, sweat secretion rate is found to be normal....

  8. Children’s cortisol and salivary alpha-amylase interact to predict attention bias to threatening stimuli

    OpenAIRE

    Ursache, Alexandra; Blair, Clancy

    2014-01-01

    Physiological responses to threat occur through both the autonomic nervous system (ANS) and the hypothalamic pituitary adrenal (HPA) axis. Activity in these systems can be measured through salivary alpha-amylase (sAA) and salivary cortisol, respectively. Theoretical work and empirical studies have suggested the importance of examining the coordination of these systems in relation to cognitive functioning and behavior problems. Less is known, however, about whether these systems interactively ...

  9. Parachute Jumping Induces More Sympathetic Activation Than Cortisol Secretion in First-Time Parachutists

    OpenAIRE

    Chieffi; Viggiano; Tafuri; Cibelli; Valenzano; Triggiani; Messina; Luca; Monda

    2016-01-01

    Background The word “stress” describes the status of the body affected by external or internal forces, or “stressors”, threatening to alter its dynamic balance or homeostasis. The adaptive changes which occur in reply to stressors are either behavioral or physical. Once a given threshold is surpassed, a systemic reaction takes place involving the “stress system” in the brain together with its peripheral components, the hypothalamic-pituitary-adrenal axis and autonomic sympathetic...

  10. Stress influencing production and welfare in farmed mink

    DEFF Research Database (Denmark)

    Malmkvist, Jens

    2012-01-01

    Results linking stress, production and welfare in farmed mink, with special focus on the hypothalamic-pituitary-adrenal (HPA)-axis, are presented. Interpretation of stress responses are discussed, combining context, neuroendocrine and behavioural indicators. Results from the development and valid...... animals and whether fur-chewing/stereotypic behaviour is associated with hippocampal neurogenesis in mink. Perspectives and suggested future research aiming to improve production and welfare in farmed mink are given....

  11. Neural Correlates of the Cortisol Awakening Response in Humans

    OpenAIRE

    Boehringer, Andreas; Tost, Heike; Haddad, Leila; Lederbogen, Florian; Wüst, Stefan; Schwarz, Emanuel; Meyer-Lindenberg, Andreas

    2015-01-01

    The cortisol rise after awakening (cortisol awakening response, CAR) is a core biomarker of hypothalamic-pituitary-adrenal (HPA) axis regulation related to psychosocial stress and stress-related psychiatric disorders. However, the neural regulation of the CAR has not been examined in humans. Here, we studied neural regulation related to the CAR in a sample of 25 healthy human participants using an established psychosocial stress paradigm together with multimodal functional and structural (vox...

  12. Larger adaptive response of 5-HT1A autoreceptors to chronic fluoxetine in a mouse model of depression than in healthy mice

    Institute of Scientific and Technical Information of China (English)

    N.FROGER; E.PALAZZO; T.RENOIR; M.MELFORT; N.BARDEN; M.HAMON; L.LANFUMEY

    2004-01-01

    Vulnerability to major depressive disorders, in particular depression, is often associated with both hypoactivity of the central serotoninergic (5-HT) system and hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. Extensive studies in normal healthy rodents showed that chronic treatment with SSRI antidepressants produced a marked functional desensitization of somatodendritic 5-HT1A autoreceptors, and this adaptive change has been claimed to play a key role in the therapeutic action of

  13. Update of sleep alterations in depression

    OpenAIRE

    Andrés Barrera Medina; DeboraYoaly Arana Lechuga; Oscar Sánchez Escandón; Javier Velázquez Moctezuma

    2014-01-01

    Sleep disturbances in depression are up to 70%. Patients frequently have difficulty in falling asleep, frequent awakenings during the night and non-restorative sleep. Sleep abnormalities in depression are mainly characterized by increased rapid eye movement (REM) sleep and reduced slow wave sleep. Among the mechanisms of sleep disturbances in depression are hyperactivation of the hypothalamic-pituitary-adrenal axis, CLOCK gene polymorphism and primary sleep disorders. The habenula is a struct...

  14. Association of Cortisol and the Metabolic Syndrome in Korean Men and Women

    OpenAIRE

    Park, Sat Byul; Blumenthal, James A.; Lee, Soon Young; Georgiades, Anastasia

    2011-01-01

    Obesity and the metabolic syndrome are closely related and have become increasingly prevalent in Korea. The cardiovascular disease (CVD) risk factors comprising the metabolic syndrome have previously been associated with increased hypothalamic-pituitary-adrenal axis (HPAA) activity, but the associations have not been extensively examined in non-Caucasian populations. The aim of the present study was to investigate the relationships between cortisol, adiposity and the metabolic syndrome in a K...

  15. Persistent dizziness and recurrent syncope due to HIV-associated Addison’s disease: Case report from a resource-limited setting

    Directory of Open Access Journals (Sweden)

    D Kibirige

    2012-09-01

    Full Text Available Addison’s disease or primary adrenal insufficiency is a well-recognised fatal endocrine condition among HIV-infected patients. HIV infection is associated with adrenal gland destruction and profound disruption of the hypothalamic-pituitary adrenal axis. We describe a case of HIV-associated Addison’s disease in a 58-year-old newly diagnosed HIV-seropositive male patient, highlighting its occurrence in this era of HIV/AIDS pandemic.

  16. Psychobiology of anorexia nervosa.

    Science.gov (United States)

    Ploog, D W; Pirke, K M

    1987-11-01

    The psychobiology of anorexia nervosa is described and explained under four headings; (1) the psychopathology as related to the motivation for fasting; (2) metabolic and somatic consequences of starvation, including brain morphology; (3) endocrine abnormalities in the hypothalamic-pituitary-adrenal and gonadal axis; and (4) the hunger drive and its possible perversions in terms of aspects of neuroethology and the reward system in the brain.

  17. Adrenal insufficiency.

    Science.gov (United States)

    Li-Ng, Melissa; Kennedy, Laurence

    2012-10-01

    Adrenocortical insufficiency may arise through primary failure of the adrenal glands or due to lack of ACTH stimulation as a result of pituitary or hypothalamic dysfunction. Prolonged administration of exogenous steroids will suppress the hypothalamic-pituitary-adrenal axis, and hence cortisol secretion. We review briefly the causes, investigation, and treatment of adrenal insufficiency, and highlight aspects of particular relevance to patients with adrenal tumors.

  18. Effect of fish oil and coconut fat supplementation on depressive-type behavior and corticosterone levels of prenatally stressed male rats

    OpenAIRE

    Borsonelo, Elizabethe Cristina [UNIFESP; Suchecki, Deborah; Galduróz, José Carlos Fernandes [UNIFESP

    2011-01-01

    Prenatal stress (PNS) during critical periods of brain development has been associated with numerous behavioral and/or mood disorders in later life. These outcomes may result from changes in the hypothalamic-pituitary-adrenal (HPA) axis activity, which, in turn, can be modulated by environmental factors, such as nutritional status. in this study, the adult male offspring of dams exposed to restraint stress during the last semester of pregnancy and fed different diets were evaluated for depres...

  19. Potential Association of Posttraumatic Stress Disorder and Decreased Bone Mineral Density in Repatriated Prisoners of War

    Science.gov (United States)

    2011-03-01

    30. Chrousos GP : The role of stress and the hypothalamic-pituitary-adrenal axis in the pathogenesis of the metabolic syndrome: neuro- endocrine ...and target tissue-related causes . Int J Obesity 2000 ; 24 (Suppl 2) : S50 – S55 . 31. Papanicolaou DA , Wilder RL , Manolagas SC...Presentation . International Society for Traumatic Stress Studies , New Orleans, Louisiana , December, 2001 . 40. Moore JL , Larrabee GJ , Ambrose MR

  20. Chronic Heroin Dependence Leading to Adrenal Insufficiency

    Directory of Open Access Journals (Sweden)

    Gautam Das

    2014-01-01

    Full Text Available Opioids have been the mainstay for pain relief and palliation over a long period of time. They are commonly abused by drug addicts and such dependence usually imparts severe physiologic effects on multiple organ systems. The negative impact of opioids on the endocrine system is poorly understood and often underestimated. We describe a patient who developed severe suppression of the hypothalamic-pituitary adrenal (HPA axis leading to secondary adrenal insufficiency due to long standing abuse of opioids.

  1. The Examination of Mindfulness, Stress, and Eating Behaviors in Mothers of Young Children

    OpenAIRE

    Kennedy, Lauren Elaine

    2016-01-01

    With the alarming prevalence of overweight and obesity, it is important to explore new approaches and strategies to improve dietary quality and weight status. Recently, a neuropsychological model of obesity was proposed. This new model illustrates an evidencebased relationship between a chronically activated hypothalamic-pituitary-adrenal (HPA) axis, due to chronic psychological stress and mood disturbance, and the food reward-related mechanisms within the brain. Intensive mind...

  2. Differential regulation of parvocellular neuronal activity in the paraventricular nucleus of the hypothalamus following single versus repeated episodes of water restriction-induced drinking

    OpenAIRE

    2007-01-01

    Acute activation of the hypothalamic-pituitary-adrenal (HPA) axis releases glucocorticoids to maintain homeostasis, whereas prolonged exposure to elevated glucocorticoids has deleterious effects. Due to the potential benefits of limiting stress-induced glucocorticoid secretion, the present study uses drinking in dehydrated rats as a model to delineate mechanisms mobilized to rapidly inhibit HPA activity during stress. Using Fos expression as an indicator of neuronal activation, the effect of ...

  3. Impaired hypothalamic-pituitary-testicular axis activity, spermatogenesis, and sperm function promote infertility in males with lead poisoning.

    Science.gov (United States)

    Gandhi, Jason; Hernandez, Rafael J; Chen, Andrew; Smith, Noel L; Sheynkin, Yefim R; Joshi, Gargi; Khan, Sardar Ali

    2017-02-10

    Lead poisoning is a stealthy threat to human physiological systems as chronic exposure can remain asymptomatic for long periods of time before symptoms manifest. We presently review the biophysical mechanisms of lead poisoning that contribute to male infertility. Environmental and occupational exposure of lead may adversely affect the hypothalamic-pituitary-testicular axis, impairing the induction of spermatogenesis. Dysfunction at the reproductive axis, namely testosterone suppression, is most susceptible and irreversible during pubertal development. Lead poisoning also appears to directly impair the process of spermatogenesis itself as well as sperm function. Spermatogenesis issues may manifest as low sperm count and stem from reproductive axis dysfunction or testicular degeneration. Generation of excessive reactive oxygen species due to lead-associated oxidative stress can potentially affect sperm viability, motility, DNA fragmentation, membrane lipid peroxidation, capacitation, hyperactivation, acrosome reaction, and chemotaxis for sperm-oocyte fusion, all of which can contribute to deter fertilization. Reproductive toxicity has been tested through cross-sectional analysis studies in humans as well as in vivo and in vitro studies in animals.

  4. [Contributions of cortisol suppression tests to understanding of psychiatric disorders: a narrative review of literature].

    Science.gov (United States)

    Tajima-Pozo, Kazuhiro; Montes-Montero, Ana; Güemes, Itziar; González-Vives, Sara; Díaz-Marsá, Marina; Carrasco, José Luis

    2013-01-01

    Activity of the hypothalamic-pituitary-adrenal axis had been studied for the past half century, when some researchers noted that some patients with Cushing's syndrome and severe mood disorders had high baseline cortisol levels, which resulted in an inhibited response in the 1mg dexamethasone suppression test. Altered dexamethasone suppression test results were subsequently found in many psychiatric diseases, including anorexia nervosa, obsessive-compulsive disorder, degenerative dementia, bipolar disorders, and schizophrenia. The relationship between high baseline cortisol levels and stress has also been studied. Some researches on the genesis of borderline personality disorder focused on traumatic childhood backgrounds. Other investigations aimed at elucidating the relationship between traumatic backgrounds and some psychiatric disorders noted that patients with post-traumatic stress disorder and borderline personality disorder showed an enhanced cortisol suppression with low cortisol doses (0.5 mg). Recent studies showed that use of an ultra-low dose of cortisol during the dexamethasone suppression test may be helpful for detecting disorders with hyperactivity of the hypothalamic-pituitary-adrenal axis. Recent advances in neuroimaging support the existence of hyperactivity of the hypothalamic-pituitary-adrenal axis in patients with borderline personality disorder, relating a decreased pituitary gland volume to major traumatic backgrounds and suicidal attempts. The purpose of this paper is to make a narrative review of research using dexamethasone suppression test in psychiatric disorders, in order to ascertain its value as a supplemental diagnostic test or as a prognostic marker. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

  5. Positive Association Between Posterior Subgenual Cingulate and Pituitary Volumes in Psychotic Major Depression

    Directory of Open Access Journals (Sweden)

    Konstantina Vassilopoulou

    2015-03-01

    Full Text Available Posterior subgenual cingulate cortex has been consistently linked with the pathophysiology of major depression in both structural and functional brain imaging studies. Likewise, the hyperactivity of the hypothalamic-pituitary-adrenal axis in major depression is well established, especially in its psychotic subtype. Moreover, posterior subgenual cingulate cortex exerts an inhibitory effect on the hypothalamic-pituitary-adrenal axis. While studies show pituitary volume to be a valid marker of hypothalamic-pituitary-adrenal axis activity, none have investigated the volumetric relationships between posterior subgenual cingulate cortex and pituitary volume in subtypes of major depressive disorder, which was precisely the aim of our study. We hypothesized a differential volumetric relationship in psychotic depression. We assessed posterior subgenual cingulate and pituitary volume using Magnetic Resonance Imaging scanning and investigated their volumetric relationships in 39 patients with major depressive disorder (17 psychotic and 22 melancholic and 18 normal controls. We found strong positive correlations between both left and right posterior subgenual volumes and pituitary volume only in the psychotic depression group (left: rs=0.77, p<0.001, right: rs=0.67, p=0.003. These positive associations were confirmed by regression analyses controlling for patient’s age and type of medications. By contrast, no significant volumetric associations were detected in the groups of melancholic patients and normal controls. Our findings provide support to the hypothesis that posterior subgenual cingulate is differentially involved in the pathophysiology of psychotic symptoms in major depressive disorder.

  6. The Impact of Microbiota-Gut-Brain Axis on Diabetic Cognition Impairment

    Directory of Open Access Journals (Sweden)

    Youhua Xu

    2017-04-01

    Full Text Available Progressive cognitive dysfunction is a central characteristic of diabetic encephalopathy (DE. With an aging population, the incidence of DE is rising and it has become a major threat that seriously affects public health. Studies within this decade have indicated the important role of risk factors such as oxidative stress and inflammation on the development of cognitive impairment. With the recognition of the two-way communication between gut and brain, recent investigation suggests that “microbiota-gut-brain axis” also plays a pivotal role in modulating both cognition function and endocrine stability. This review aims to systemically elucidate the underlying impact of diabetes on cognitive impairment.

  7. Salmonella impairs CD8 T cell response through PD-1: PD-L axis.

    Science.gov (United States)

    López-Medina, Marcela; Carrillo-Martín, Ismael; Leyva-Rangel, Jessica; Alpuche-Aranda, Celia; Ortiz-Navarrete, Vianney

    2015-12-01

    We have shown that Salmonella remains for a long period of time within B cells, plasma cells, and bone marrow B cell precursors, which might allow persistence and dissemination of infection. Nonetheless, how infected cells evade CD8 T cell response has not been characterized. Evidence indicates that some pathogens exploit the PD-1: PD-L (PD-L1 and PD-L2) interaction to inhibit CD8 T cells response to contribute the chronicity of the infection. To determine whether the PD-1: PD-L axis plays a role during Salmonella infection; we evaluated PD-1 expression in antigen-specific CD8 T cells and PD-1 ligands in Salmonella-infected cells. Our results show that infected B cells and macrophages express continuously co-stimulatory (CD40, CD80, and CD86) and inhibitory molecules (PD-L1 and PD-L2) in early and late stages of chronic Salmonella infection, while antigen-specific CD8 T cells express in a sustained manner PD-1 in the late stages of infection. Blocking this axis restores the ability of the CD8 T cells to proliferate and eliminate primary infected APCs. Therefore, a continuous PD-1: PDL interaction might be a mechanism employed by Salmonella to negatively regulate Salmonella-specific CD8 T cell cytotoxic response in order to remain within the host for a long period of time.

  8. Normal Sweat Secretion Despite Impaired Growth Hormone-Insulin-Like Growth Factor-I Axis in Obese Subjects

    Directory of Open Access Journals (Sweden)

    Michael Højby Rasmussen

    2011-01-01

    Full Text Available Adults with GH deficiency are known to exhibit reduced sweating. Whether sweating capacity is impacted in obese subjects with impaired GH secretion have not previously been investigated. The main objective was to investigate sweat secretion rate and the GH-IGF-I axis in obese subjects before and after weight loss. Sixteen severely obese women (BMI, 40.6 ± 1.1 kg/m2 were investigated before and after a diet-induced weight loss. Sixteen age-matched nonobese women served as controls. The obese subjects presented the characteristic decreased GH release, hyperinsulinaemia, increased FFA levels, and impaired insulin sensitivity, which all were normalised after diet-induced weight loss of 30 ± 5 kg. Sweat secretion rates were similar comparing obese and nonobese subjects (78 ± 10 versus 82 ± 9 mg/30 minutes and sweat secretion did not change after a diet-induced weight loss in obese subjects. We conclude that although obese subjects have markedly reduced GH release and impaired IGF-I levels, sweat secretion rate is found to be normal.

  9. A complement-microglial axis drives synapse loss during virus-induced memory impairment.

    Science.gov (United States)

    Vasek, Michael J; Garber, Charise; Dorsey, Denise; Durrant, Douglas M; Bollman, Bryan; Soung, Allison; Yu, Jinsheng; Perez-Torres, Carlos; Frouin, Arnaud; Wilton, Daniel K; Funk, Kristen; DeMasters, Bette K; Jiang, Xiaoping; Bowen, James R; Mennerick, Steven; Robinson, John K; Garbow, Joel R; Tyler, Kenneth L; Suthar, Mehul S; Schmidt, Robert E; Stevens, Beth; Klein, Robyn S

    2016-06-22

    Over 50% of patients who survive neuroinvasive infection with West Nile virus (WNV) exhibit chronic cognitive sequelae. Although thousands of cases of WNV-mediated memory dysfunction accrue annually, the mechanisms responsible for these impairments are unknown. The classical complement cascade, a key component of innate immune pathogen defence, mediates synaptic pruning by microglia during early postnatal development. Here we show that viral infection of adult hippocampal neurons induces complement-mediated elimination of presynaptic terminals in a murine WNV neuroinvasive disease model. Inoculation of WNV-NS5-E218A, a WNV with a mutant NS5(E218A) protein leads to survival rates and cognitive dysfunction that mirror human WNV neuroinvasive disease. WNV-NS5-E218A-recovered mice (recovery defined as survival after acute infection) display impaired spatial learning and persistence of phagocytic microglia without loss of hippocampal neurons or volume. Hippocampi from WNV-NS5-E218A-recovered mice with poor spatial learning show increased expression of genes that drive synaptic remodelling by microglia via complement. C1QA was upregulated and localized to microglia, infected neurons and presynaptic terminals during WNV neuroinvasive disease. Murine and human WNV neuroinvasive disease post-mortem samples exhibit loss of hippocampal CA3 presynaptic terminals, and murine studies revealed microglial engulfment of presynaptic terminals during acute infection and after recovery. Mice with fewer microglia (Il34(-/-) mice with a deficiency in IL-34 production) or deficiency in complement C3 or C3a receptor were protected from WNV-induced synaptic terminal loss. Our study provides a new murine model of WNV-induced spatial memory impairment, and identifies a potential mechanism underlying neurocognitive impairment in patients recovering from WNV neuroinvasive disease.

  10. Social facilitation of wound healing.

    Science.gov (United States)

    Detillion, Courtney E; Craft, Tara K S; Glasper, Erica R; Prendergast, Brian J; DeVries, A Courtney

    2004-09-01

    It is well documented that psychological stress impairs wound healing in humans and rodents. However, most research effort into influences on wound healing has focused on factors that compromise, rather than promote, healing. In the present study, we determined if positive social interaction, which influences hypothalamic-pituitary-adrenal (HPA) axis activity in social rodents, promotes wound healing. Siberian hamsters received a cutaneous wound and then were exposed to immobilization stress. Stress increased cortisol concentrations and impaired wound healing in isolated, but not socially housed, hamsters. Removal of endogenous cortisol via adrenalectomy eliminated the effects of stress on wound healing in isolated hamsters. Treatment of isolated hamsters with oxytocin (OT), a hormone released during social contact and associated with social bonding, also blocked stress-induced increases in cortisol concentrations and facilitated wound healing. In contrast, treating socially housed hamsters with an OT antagonist delayed wound healing. Taken together, these data suggest that social interactions buffer against stress and promote wound healing through a mechanism that involves OT-induced suppression of the HPA axis. The data imply that social isolation impairs wound healing, whereas OT treatment may ameliorate some effects of social isolation on health.

  11. The effects of social isolation on wound healing mechanisms in female mice.

    Science.gov (United States)

    Pyter, Leah M; Yang, Linglan; da Rocha, José M; Engeland, Christopher G

    2014-03-29

    Various stressors impair wound healing in humans and rodents. For example, social isolation delays wound closure in rodents, but the healing mechanisms that underlie this delay have yet to be identified. Here, the effects of three weeks of social isolation on hypothalamic-pituitary-adrenal axis responses and healing factors involved in the inflammatory and proliferative phases of wound healing were assessed in adult female hairless mice. Social isolation reduced basal circulating corticosterone concentrations and increased body and thymus weights compared with group-housed controls. Isolation impaired dermal wound closure by up to 30% and reduced initial total wound bacterial load relative to controls. Inflammatory gene expression in the wounds was not affected by the observed differences in wound bacterial load. However, isolation reduced wound gene expression of keratinocyte growth factor and vascular endothelial growth factor, which are involved in keratinocyte proliferation/migration and angiogenesis during the proliferative phase of healing. These data indicate that social isolation induces healing impairments that may be attributed to reductions in growth factors necessary for proper skin cell proliferation and blood vessel growth during healing. This healing impairment occurred in the absence of both high wound bacterial load and elevated circulating glucocorticoids, which have previously been hypothesized to be required for stress-impaired healing in mice.

  12. Fetal Alcohol Spectrum Disorders and their Transmission through Genetic and Epigenetic Mechanisms

    Directory of Open Access Journals (Sweden)

    Edward A Mead

    2014-06-01

    Full Text Available Fetal alcohol spectrum disorders (FASD are a group of related conditions that arise from prenatal exposure to maternal consumption of the teratogen, ethanol. It has been estimated that roughly 1% of children in the US suffer from FASD (Sampson et al., 1997, though in some world populations, such as inhabitants of some poorer regions of South Africa, the rate can climb to as high as 20% (May et al., 2013. FASD are the largest cause of mental retardation in U.S. neonates, and ironically, are entirely preventable. FASD has been linked to major changes in the hypothalamic-pituitary-adrenal (HPA axis, resulting in lifelong impairments through mental disorders, retardation, sensitivity to stress, and an impaired immune system with the related outcomes of elevated risk of cancer and other diseases. FASD arises from a complex interplay of genetic and epigenetic factors. Here, we review current literature on the topic to tease apart what is known in these areas particularly emphasizing the HPA axis dysfunction and how they tie into new studies of transgenerational inheritance in FASD.

  13. Switching adolescent high-fat diet to adult control diet restores neurocognitive alterations

    Directory of Open Access Journals (Sweden)

    Chloe Boitard

    2016-11-01

    Full Text Available In addition to metabolic and cardiovascular disorders, obesity is associated with adverse cognitive and emotional outcomes. Its growing prevalence in adolescents is particularly alarming since this is a period of ongoing maturation for brain structures (including the hippocampus and amygdala and for the hypothalamic-pituitary-adrenal (HPA stress axis, which is required for cognitive and emotional processing. We recently demonstrated that adolescent, but not adult, high-fat diet (HF exposure leads to impaired hippocampal function and enhanced amygdala function through HPA axis alteration (Boitard et al., 2014; Boitard et al., 2012; Boitard et al., 2015. Here, we assessed whether the effects of adolescent HF consumption on brain function are permanent or reversible. After adolescent exposure to HF, switching to a standard chow diet restored levels of hippocampal neurogenesis and normalized enhanced HPA axis reactivity, amygdala activity and avoidance memory. Therefore, while the adolescent period is highly vulnerable to the deleterious effects of diet-induced obesity, adult exposure to a standard diet appears sufficient to reverse alterations of brain function.

  14. Effects of hyperlipidaemia on glucocorticoid metabolism: results of a randomized controlled trial in healthy young women.

    Science.gov (United States)

    Mai, K; Reinecke, F; Andres, J; Bobbert, T; Kraatz, J; Wudy, S A; Hartmann, M F; Maser-Gluth, C; Pfeiffer, A F H; Spranger, J

    2011-05-01

    It is well established that the hypothalamic-pituitary-adrenal (HPA) axis is altered in obese individuals. Hyperlipidaemia with elevated levels of free fatty acids (FFAs) is also frequently seen in obesity and in the metabolic syndrome. We hypothesized, therefore, that hyperlipidaemia may alter the activity of the HPA axis. The effects of hyperlipidaemia, including increased circulating FFAs, on ACTH secretion and cortisol metabolism were analysed in 13 healthy young women during the early follicular phase of two subsequent cycles. We administered a 20% lipid/heparin (LHI) or a saline/heparin infusion (SHI) using a crossover design in random order for 330 min. A detailed characterization of glucocorticoid metabolism was performed by measurement of plasma ACTH, cortisol and urinary excretion rates of adrenal glucocorticoids and the glucocorticoid metabolites. We observed that LHI-induced hyperlipidaemia elevated serum cortisol levels compared to SHI. No changes in plasma ACTH levels, daily urinary excretion rates of adrenal glucocorticoids, glucocorticoid precursors/metabolites and the calculated activities of the 5α-reductase, 3β-hydroxysteroid dehydrogenase (HSD), 11-, 17-, 21-hydroxylase and 11β-HSD 1 or 2 were found. Our randomized controlled trial suggests that the adrenal sensitivity to ACTH may be enhanced by LHI-induced hyperlipidaemia in normal-weight healthy young women. This effect might contribute to the disturbances of the HPA axis described in women with abdominal obesity and impaired lipid metabolism. © 2011 Blackwell Publishing Ltd.

  15. Role of the brain-gut axis in the pathophysiology of Crohn's disease.

    Science.gov (United States)

    Stasi, Cristina; Orlandelli, Ermes

    2008-01-01

    Studies on the interaction between the central nervous system and the gastrointestinal system have shed light on the neurobiological response to stress via the hypothalamic-pituitary-adrenal and the hypothalamic-autonomic nervous system axes. These findings support a role of psychological and environmental factors in the course of gastrointestinal disorders and their influence on the neuroendocrine regulation of the immune system. Crohn's disease (CD) is a chronic inflammatory condition of the gastrointestinal tract, whose etiology involves genetic, psychological, immune and inflammatory factors. A higher prevalence of psychiatric diagnosis has been observed in CD patients. Both longitudinal and cross-sectional studies have explored the relationship between psychological stress and severity and/or clinical course of CD, with different, even conflicting, results. In several chronic diseases and stress-related psychological disorders, an alteration has been observed of the HPA response that through glucocorticoids modulate the immune/inflammatory reaction. In animal models of colitis, psychological or environmental stress may increase gastrointestinal permeability, allowing abnormal antigen presentation to the immune system and leading to the exacerbation and perpetuation of intestinal inflammation. The increased intestinal permeability under stress is mediated by corticotropin-releasing hormone stimulation through nicotinic, adrenergic and cholinergic receptors, suggesting a complex interplay between sympathetic and parasympathetic nervous systems. This review will examine and discuss the relationship between psychological stress and CD, investigating the role played by the hypothalamic-pituitary-adrenal and the hypothalamic-autonomic nervous system axes in stress-related psychological disorders, and the possible influence of chronic stress on the intestinal inflammation, in particular in CD.

  16. Prenatal Stress, Prematurity, and Asthma.

    Science.gov (United States)

    Medsker, Brock; Forno, Erick; Simhan, Hyagriv; Celedón, Juan C

    2015-12-01

    Asthma is the most common chronic disease of childhood, affecting millions of children in the United States and worldwide. Prematurity is a risk factor for asthma, and certain ethnic or racial minorities such as Puerto Ricans and non-Hispanic blacks are disproportionately affected by both prematurity and asthma. In this review, we examine current evidence to support maternal psychosocial stress as a putative link between prematurity and asthma, while also focusing on disruption of the hypothalamic-pituitary-adrenal (HPA) axis and immune responses as potential underlying mechanisms for stress-induced "premature asthma." Prenatal stress may cause not only abnormalities in the HPA axis but also epigenetic changes in the fetal glucocorticoid receptor gene (NR3C1), leading to impaired glucocorticoid metabolism. Moreover, maternal stress can alter fetal cytokine balance, favoring TH2 (allergic) immune responses characteristic of atopic asthma: interleukin 6 (IL-6), which has been associated with premature labor, can promote TH2 responses by stimulating production of IL-4 and IL-13. Given a link among stress, prematurity, and asthma, future research should include birth cohorts aimed at confirming and better characterizing "premature asthma." If confirmed, clinical trials of prenatal maternal stress reduction would be warranted to reduce the burden of these common comorbidities. While awaiting the results of such studies, sound policies to prevent domestic and community violence (eg, from firearms) are justified, not only by public safety but also by growing evidence of detrimental effects of violence-induced stress on psychiatric and somatic health.

  17. Sex-dependent role of glucocorticoids and androgens in the pathophysiology of human obesity.

    Science.gov (United States)

    Pasquali, R; Vicennati, V; Gambineri, A; Pagotto, U

    2008-12-01

    Obesity, particularly its abdominal phenotype, a harbinger of the metabolic syndrome, cardiovascular diseases (CVDs) and type 2 diabetes mellitus (T2D), is becoming one of the most significant public health problems worldwide. Among many other potential factors, derangement of multiple hormone systems have increasingly been considered for their potential importance in the pathophysiology of obesity and the metabolic syndrome, with particular reference to glucocorticoids and sex hormones. These systems have a fundamental and coordinating role in the physiology of intermediate metabolism and cardiovascular function, and in the response to acute and chronic stress challenge. Abdominal obesity is associated with a hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and impaired androgen balance, although these alterations differ according to sex. As there is also increasing evidence that there are many differences between the sexes in the susceptibility and development of obesity, T2D and CVDs, we support the hypothesis that alterations of the HPA axis and androgen balance may have an important function in this context. This is further supported by the fact that there are important differences between males and females in their ability to adapt to both internal and particularly to environmental (external) stressors. In addition, there is also evidence that, in both physiological and pathological conditions, a close cross talk exists between sex hormones and glucocorticoids at both neuroendocrine and peripheral level, again with different specificities according to sex.

  18. Changes in stress-stimulated allopregnanolone levels induced by neonatal estradiol treatment are associated with enhanced dopamine release in adult female rats: reversal by progesterone administration.

    Science.gov (United States)

    Porcu, Patrizia; Lallai, Valeria; Locci, Andrea; Catzeddu, Sandro; Serra, Valeria; Pisu, Maria Giuseppina; Serra, Mariangela; Dazzi, Laura; Concas, Alessandra

    2017-03-01

    Allopregnanolone plays a role in the stress response and homeostasis. Alterations in the estrogen milieu during the perinatal period influence brain development in a manner that persists into adulthood. Accordingly, we showed that a single administration of estradiol benzoate (EB) on the day of birth decreases brain allopregnanolone concentrations in adult female rats. We examined whether the persistent decrease in allopregnanolone concentrations, induced by neonatal EB treatment, might affect sensitivity to stress during adulthood. Female rats were treated with 10 μg of EB or vehicle on the day of birth. During adulthood, the response to acute foot shock stress was assessed by measuring changes in brain allopregnanolone and corticosterone levels, as well as extracellular dopamine output in the medial prefrontal cortex (mPFC). Neonatal EB treatment enhanced stress-stimulated allopregnanolone levels in the hypothalamus, as well as extracellular dopamine output in the mPFC; this latest effect is reverted by subchronic progesterone treatment. By contrast, neonatal EB treatment did not alter stress-induced corticosterone levels, sensitivity to hypothalamic-pituitary-adrenal (HPA) axis negative feedback, or abundance of glucocorticoid and mineralocorticoid receptors. The persistent decrease in brain allopregnanolone concentrations, induced by neonatal EB treatment, enhances stress-stimulated allopregnanolone levels and extracellular dopamine output during adulthood. These effects are not associated to an impairment in HPA axis activity. Heightened sensitivity to stress is a risk factor for several neuropsychiatric disorders; these results suggest that exposure to estrogen during development may predispose individuals to such disorders.

  19. Diabetes type II: a risk factor for depression-Parkinson-Alzheimer?

    Science.gov (United States)

    Riederer, Peter; Bartl, Jasmin; Laux, Gerd; Grünblatt, Edna

    2011-02-01

    There is ample evidence that impairments in the hypothalamic-pituitary-adrenal (HPA) axis are of etiopathobiochemical importance in a subgroup of patients with "depression", causing hypercortisolaemia as major metabolic effect. Chronic hypercortisolaemia causes insulin resistance. Therefore, it is not surprising that epidemiological studies demonstrate an association of "depression" with diabetes type II and vice versa. Chronic stress and hypercortisolaemia are conditions, which have been suggested to be causal for Alzheimer's disease (AD) as brain insulin resistance is associated with β-Amyloid-accumulation and hyperphosphorylation of tau-protein. Depression is one of the significant symptomatology preceding AD. It is however, not known whether "depression" associated with hypercortisolaemia is the subgroup at risk for AD. In contrast to a subgroup of "depression" and to AD, in Parkinson's disease (PD) there is only weak evidence for an association with diabetes type II and insulin resistance. As "depression" is preceding PD in up to half of such patients, it remains to be elucidated whether this is a subgroup of depressed patients, which is not associated with disturbances of the HPA axis and hypercortisolaemia. Improved clinical and biochemical/molecular knowledge about "depression" associated with AD and PD in comparison to "pure" depression might lead to improved therapeutic strategies and even drug development focusing subtypes of "depression".

  20. Adult hippocampal neurogenesis buffers stress responses and depressive behaviour.

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    Snyder, Jason S; Soumier, Amélie; Brewer, Michelle; Pickel, James; Cameron, Heather A

    2011-08-03

    Glucocorticoids are released in response to stressful experiences and serve many beneficial homeostatic functions. However, dysregulation of glucocorticoids is associated with cognitive impairments and depressive illness. In the hippocampus, a brain region densely populated with receptors for stress hormones, stress and glucocorticoids strongly inhibit adult neurogenesis. Decreased neurogenesis has been implicated in the pathogenesis of anxiety and depression, but direct evidence for this role is lacking. Here we show that adult-born hippocampal neurons are required for normal expression of the endocrine and behavioural components of the stress response. Using either transgenic or radiation methods to inhibit adult neurogenesis specifically, we find that glucocorticoid levels are slower to recover after moderate stress and are less suppressed by dexamethasone in neurogenesis-deficient mice than intact mice, consistent with a role for the hippocampus in regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Relative to controls, neurogenesis-deficient mice also showed increased food avoidance in a novel environment after acute stress, increased behavioural despair in the forced swim test, and decreased sucrose preference, a measure of anhedonia. These findings identify a small subset of neurons within the dentate gyrus that are critical for hippocampal negative control of the HPA axis and support a direct role for adult neurogenesis in depressive illness.

  1. Peripheral lipopolysaccharide administration transiently affects expression of brain-derived neurotrophic factor, corticotropin and proopiomelanocortin in mouse brain.

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    Schnydrig, Sabine; Korner, Lukas; Landweer, Svenja; Ernst, Beat; Walker, Gaby; Otten, Uwe; Kunz, Dieter

    2007-12-11

    Peripheral inflammation induced by intraperitoneal (i.p.) injection of Lipopolysaccharide (LPS) is known to cause functional impairments in the brain affecting memory and learning. One of mechanisms may be the interference with neurotrophin (NT) expression and function. In the current study we administered a single, high dose of LPS (3mg/kg, i.p.) into mice and investigated changes in brain-derived neurotrophic factor (BDNF) gene expression within 1-6 days after LPS injection. Crude synaptosomes were isolated from brain tissue and subjected to Western-blot analyses. We found transient reductions in synaptosomal proBDNF- and BDNF protein expression, with a maximal decrease at day 3 as compared to saline injected controls. The time course of reduction of BDNF mRNA in whole brain extracts parallels the decrease in protein levels in synaptosomes. LPS effects in the central nervous system (CNS) are known to crucially involve the activation of the hypothalamic-pituitary-adrenal (HPA) axis. We analysed the time course of corticotropin releasing hormone (CRH)- and proopiomelanocortin (POMC) mRNA expression. As observed for BDNF-, CRH- and POMC mRNA levels are also significantly reduced on day 3 indicating a comparable time course. These results suggest that peripheral inflammation causes a reduction of trophic supply in the brain, including BDNF at synaptic sites. The mechanisms involved could be a negative feedback of the activated HPA axis.

  2. The cost of caregiving: endocrine and immune implications in elderly and non elderly caregivers.

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    Lovell, Brian; Wetherell, Mark A

    2011-05-01

    This review will provide an overview of literature that has linked caregiver stress with development and progression of disease, via interactions between the hypothalamic-pituitary-adrenal (HPA) axis and immune systems. The link between caregiver stress and dysregulation of key physiologic mediators has, in the main, focussed on elderly caregivers of spouses with degenerative illness, i.e., dementia. In these populations, aberrations of both endocrinological and immunologic mediators have been demonstrated. However, as a function of their advancing age, elderly populations experience natural dysregulation of the HPA axis and decline of immunologic efficacy. More recently, research has begun to assess whether caregiver stress exacts a similar physiologic toll on non elderly caregivers, i.e., parents of medically fragile children. Dysregulation of endocrinological and immunologic mediators have been observed in both populations, however, more consistently so in the elderly. The authors suggest that, by considering specific characteristics of the care recipient, i.e., type of impairment, and concomitant changes in the caregiving experience, i.e., caregiving intensity, as well as the role of dyadic support, researchers might be better poised to explain discrepant physiologic findings between elderly and non elderly caregivers and reconcile similar physiologic inconsistencies between different, non elderly populations.

  3. Modulation of Sleep Homeostasis by Corticotropin Releasing Hormone in REM Sleep-Deprived Rats

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    Ricardo Borges Machado

    2010-01-01

    Full Text Available Studies have shown that sleep recovery following different protocols of forced waking varies according to the level of stress inherent to each method. Sleep deprivation activates the hypothalamic-pituitary-adrenal axis and increased corticotropin-releasing hormone (CRH impairs sleep. The purpose of the present study was to evaluate how manipulations of the CRH system during the sleep deprivation period interferes with subsequent sleep rebound. Throughout 96 hours of sleep deprivation, separate groups of rats were treated i.c.v. with vehicle, CRH or with alphahelical CRH9−41, a CRH receptor blocker, twice/day, at 07:00 h and 19:00 h. Both treatments impaired sleep homeostasis, especially in regards to length of rapid eye movement sleep (REM and theta/delta ratio and induced a later decrease in NREM and REM sleep and increased waking bouts. These changes suggest that activation of the CRH system impact negatively on the homeostatic sleep response to prolonged forced waking. These results indicate that indeed, activation of the HPA axis—at least at the hypothalamic level—is capable to reduce the sleep rebound induced by sleep deprivation.

  4. Blockade of glucocorticoid receptors improves cutaneous wound healing in stressed mice.

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    de Almeida, Taís Fontoura; de Castro Pires, Taiza; Monte-Alto-Costa, Andréa

    2016-02-01

    Stress is an important condition of modern life. The successful wound healing requires the execution of three major overlapping phases: inflammation, proliferation, and remodeling, and stress can disturb this process. Chronic stress impairs wound healing through the activation of the hypothalamic-pituitary-adrenal axis, and the glucocorticoids (GCs) hormones have been shown to delay wound closure. Therefore, the aim of this study was to investigate the effects of a GC receptor antagonist (RU486) treatment on cutaneous healing in chronically stressed mice. Male mice were submitted to rotational stress, whereas control animals were not subjected to stress. Stressed and control animals were treated with RU486. A full-thickness excisional lesion was generated, and seven days later, lesions were recovered. The RU486 treatment improves wound healing since contraction takes place earlier in RU486-treated in comparison to non-treated mice, and the RU486 treatment also improves the angiogenesis in Stress+RU486 mice when compared to stressed animals. The Stress+RU486 group showed a decrease in inflammatory cell infiltration and in hypoxia-inducible factor-1α and inducible nitric oxide synthase expression; meanwhile, there was an increase in myofibroblasts quantity. In conclusion, blockade of GC receptors with RU486 partially ameliorates stress-impaired wound healing, suggesting that stress inhibits healing through more than one functional pathway. © 2016 by the Society for Experimental Biology and Medicine.

  5. Defensive coping and renovascular disease risk - Adrenal fatigue in a cohort of Africans and Caucasians: The SABPA study.

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    de Kock, Andrea; Malan, Leoné; Hamer, Mark; Cockeran, Marike; Malan, Nico T

    2015-08-01

    Defensive coping is an established cardiovascular risk factor in Africans. Additionally, chronic, excessive or inadequate hypothalamic-pituitary-adrenal axis (HPAA) stress responses could either increase or decrease cortisol responses, which may relate to renal impairment. We scrutinised the relationship between urinary cortisol levels and renovascular disease risk in Africans and Caucasians utilising defensive coping. Africans (n=168) and Caucasians (n=207) from the SABPA (Sympathetic activity and Ambulatory Blood Pressure in Africans) study were included in our analyses, excluding HIV positive, diabetic, renal impairment, and cortisone users. The Coping Strategy Indicator questionnaire assessed preferred coping responses. Ambulatory blood pressure was recorded together with 8h fasting blood and urine sampling. Renovascular disease risk markers included the albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR). The main findings revealed that Caucasians with high cortisol showed augmented renovascular disease risk. Conversely, Africans revealed low cortisol levels whilst 21.84% reported experience of severe stress, possibly depicting HPAA hypoactivity. Additionally, these Africans with low cortisol revealed increased ACR and decreased eGFR, which was further enhanced by defensive coping. Defensive coping enhanced renovascular risk in Africans, especially in those with lower cortisol, which may be due to HPAA dysfunction and/or adrenal fatigue. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Effect of Paroxetine on HPA Axis in Type 2 Diabetes Mellitus Patients with Depression%帕罗西汀对2型糖尿病并发抑郁患者HPA轴的影响

    Institute of Scientific and Technical Information of China (English)

    李杰

    2013-01-01

    [Objective]To explore the effect of paroxetine on hypothalamic-pituitary-adrenal(HPA) axis function in type 2 diabetic patients with depression.[Results] Totally 70 type 2 diabetic patients with depression were randomly divided into the observation group and the control group with 35 cases in each.The control group was given conventional therapy of diabetes mellitus,while the observation group was given paroxetine treatment on the basis of the treatment of control group.After 8 weeks of treatment,blood glucose control and depressive symptoms in two groups before and after treatment were observed.HPA axis of corticotropin releasing hormone(CRH),adrenocorticotropic hormone(ACTH) and cortisol(Cor) levels were detected.[Results]Compared before the treatment,fasting plasma glucose(FPG),2h postprandial glucose (2hPG) and Hamilton depression scale(HAMD) score in two groups obviously decreased(P <0.05 or P <0.01).The observation group was better than the control group(P <0.05).Compared with before the treatment,plasma levels of CRH,ACTH and Cor in observation group obviously decreased(P <0.05),but there was no significant difference between the observation group and control group(P <0.05).[Conclusion]Paroxetine can effectively improve blood sugar levels in type 2 diabetic patients with depression and relieve depression.Its mechanism of action may be related to the regulation of HPA axis.%[目的]探讨帕罗西汀对2型糖尿病(T2DM)并发抑郁患者下丘脑-垂体-肾上腺(HPA)轴功能的影响.[方法]将70例T2DM抑郁症患者随机分为观察组和对照组各35例.对照组给予糖尿病常规治疗,观察组在对照组基础上联用帕罗西汀治疗;用药8周后观察两组患者治疗前后血糖控制及抑郁症状改善情况,并检测HPA轴中促肾上腺皮质激素释放激素(CRH)、肾上腺皮质激素(ACTH)及皮质醇(Cor)水平变化.[结果]两组患者空腹血糖(FPG)、餐后2h血糖(2hPG)水平及汉密尔顿抑郁量

  7. A cholinergic hypothesis of the unconscious in affective disorders.

    Directory of Open Access Journals (Sweden)

    Costa eVakalopoulos

    2013-11-01

    Full Text Available The interactions between distinct pharmacological systems are proposed as a key dynamic in the formation of unconscious memories underlying rumination and mood disorder, but also reflect the plastic capacity of neural networks that can aid recovery. An inverse and reciprocal relationship is postulated between cholinergic and monoaminergic receptor subtypes. M1-type muscarinic receptor transduction facilitates encoding of unconscious, prepotent behavioural repertoires at the core of affective disorders and ADHD. Behavioural adaptation to new contingencies is mediated by the classic prototype receptor: 5-HT1A (Gi/o and its modulation of m1-plasticity. Reversal of learning is dependent on increased phasic activation of midbrain monoaminergic nuclei and is a function of hippocampal theta. Acquired hippocampal dysfunction due to abnormal activation of the hypothalamic-pituitary-adrenal (HPA axis predicts deficits in hippocampal-dependent memory and executive function and further impairments to cognitive inhibition. Encoding of explicit memories is mediated by Gq/11 and Gs signalling of monoamines only. A role is proposed for the phasic activation of the basal forebrain cholinergic nucleus by cortical projections from the complex consisting of the insula and claustrum. Although controversial. recent studies suggest a common ontogenetic origin of the two structures and a functional coupling. Lesions of the region result in loss of motivational behaviour and familiarity based judgements. A major hypothesis of the paper is that these lost faculties result indirectly, from reduced cholinergic tone.

  8. Transfer of maternal psychosocial stress to the fetus.

    Science.gov (United States)

    Rakers, Florian; Rupprecht, Sven; Dreiling, Michelle; Bergmeier, Christoph; Witte, Otto W; Schwab, Matthias

    2017-02-22

    Psychosocial maternal stress experienced during different vulnerable periods throughout gestation is thought to increase the individual's risk to develop neuropsychiatric, cardiovascular and metabolic disease in later life. Cortisol has generally been identified as the major mediator of maternal stress transfer to the fetus. Its lipophilic nature allows a trans-placental passage and thus excessive maternal cortisol could persistently impair the development of the fetal hypothalamic-pituitary-adrenal axis (HPAA). However, cortisol alone cannot fully explain all effects of maternal stress especially during early to mid pregnancy before maturation of the fetal HPAA has even begun and expression of fetal glucocorticoid receptors is limited. This review focuses on mediators of maternal fetal stress transfer that in addition to cortisol have been proposed as transmitters of maternal stress: catecholamines, cytokines, serotonin/tryptophan, reactive-oxygen-species and the maternal microbiota. We propose that the effects of psychosocial maternal stress on fetal development and health and disease in later life are not a consequence of a single pathway but are mediated by multiple stress-transfer mechanisms acting together in a synergistic manner.

  9. Stress control and human nutrition.

    Science.gov (United States)

    Takeda, Eiji; Terao, Junji; Nakaya, Yutaka; Miyamoto, Ken-ichi; Baba, Yoshinobu; Chuman, Hiroshi; Kaji, Ryuji; Ohmori, Tetsuro; Rokutan, Kazuhito

    2004-08-01

    Stress is a pervasive factor in everyday life that critically affects development and functioning. Severe and prolonged stress exposure impairs homeostatic mechanisms, particularly associated with the onset of depressive illness. Brain food is aimed at preventing as well as treating a growing number of stress-related mental disorders. Some topics on the association of stress and nutrition is reviewed. (1) An increased activity of serotonergic neurons in the brain is an established consequence of stress. An increase in brain tryptophan levels on the order of that produced by eating a carbohydrate-rich/protein-poor meal causes parallel increases in the amounts of serotonin released into synapses. (2) Eating is thought to be suppressed during stress, due to anorectic effects of corticotrophin releasing hormone, and increased during recovery from stress, due to appetite stimulating effects of residual cortisol. (3) A strong inverse association between coffee intake and risk of suicide. (4) Night eating syndrome has been found to occur during periods of stress and is associated with poor results at attempts to lose weight and disturbances in the hypothalamic-pituitary-adrenal axis. (5) Dietary antioxidants present in fruits and vegetables may improve cognitive function. Therefore, it is concluded that the establishment of functional foods that correctly regulate stress response must be firmly based upon scientific knowledge and legal regulation.

  10. Acute Inflammatory Bowel Disease Complicating Chronic Alcoholism and Mimicking Carcinoid Syndrome

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    Piercarlo Ballo

    2012-08-01

    Full Text Available We report the case of a woman with a history of chronic alcohol abuse who was hospitalized with diarrhea, severe hypokalemia refractory to potassium infusion, nausea, vomiting, abdominal pain, alternations of high blood pressure with phases of hypotension, irritability and increased urinary 5-hydroxyindoleacetic acid and cortisol. Although carcinoid syndrome was hypothesized, abdominal computed tomography and colonoscopy showed non-specific inflammatory bowel disease with severe colic wall thickening, and multiple colic biopsies confirmed non-specific inflammation with no evidence of carcinoid cells. During the following days diarrhea slowly decreased and the patient’s condition progressively improved. One year after stopping alcohol consumption, the patient was asymptomatic and serum potassium was normal. Chronic alcohol exposure is known to have several deleterious effects on the intestinal mucosa and can favor and sustain local inflammation. Chronic alcohol intake may also be associated with high blood pressure, behavior disorders, abnormalities in blood pressure regulation with episodes of hypotension during hospitalization due to impaired baroreflex sensitivity in the context of an alcohol withdrawal syndrome, increased urinary 5-hydroxyindoleacetic acid as a result of malabsorption syndrome, and increased urinary cortisol as a result of hypothalamic-pituitary-adrenal axis dysregulation. These considerations, together with the regression of symptoms and normalization of potassium levels after stopping alcohol consumption, suggest the intriguing possibility of a alcohol-related acute inflammatory bowel disease mimicking carcinoid syndrome.

  11. Acute inflammatory bowel disease complicating chronic alcoholism and mimicking carcinoid syndrome.

    Science.gov (United States)

    Ballo, Piercarlo; Dattolo, Pietro; Mangialavori, Giuseppe; Ferro, Giuseppe; Fusco, Francesca; Consalvo, Matteo; Chiodi, Leandro; Pizzarelli, Francesco; Zuppiroli, Alfredo

    2012-05-01

    We report the case of a woman with a history of chronic alcohol abuse who was hospitalized with diarrhea, severe hypokalemia refractory to potassium infusion, nausea, vomiting, abdominal pain, alternations of high blood pressure with phases of hypotension, irritability and increased urinary 5-hydroxyindoleacetic acid and cortisol. Although carcinoid syndrome was hypothesized, abdominal computed tomography and colonoscopy showed non-specific inflammatory bowel disease with severe colic wall thickening, and multiple colic biopsies confirmed non-specific inflammation with no evidence of carcinoid cells. During the following days diarrhea slowly decreased and the patient's condition progressively improved. One year after stopping alcohol consumption, the patient was asymptomatic and serum potassium was normal. Chronic alcohol exposure is known to have several deleterious effects on the intestinal mucosa and can favor and sustain local inflammation. Chronic alcohol intake may also be associated with high blood pressure, behavior disorders, abnormalities in blood pressure regulation with episodes of hypotension during hospitalization due to impaired baroreflex sensitivity in the context of an alcohol withdrawal syndrome, increased urinary 5-hydroxyindoleacetic acid as a result of malabsorption syndrome, and increased urinary cortisol as a result of hypothalamic-pituitary-adrenal axis dysregulation. These considerations, together with the regression of symptoms and normalization of potassium levels after stopping alcohol consumption, suggest the intriguing possibility of a alcohol-related acute inflammatory bowel disease mimicking carcinoid syndrome.

  12. Chronic Stress Induces Structural Alterations in Splenic Lymphoid Tissue That Are Associated with Changes in Corticosterone Levels in Wistar-Kyoto Rats

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    María Eugenia Hernandez

    2013-01-01

    Full Text Available Major depressive disorder patients present chronic stress and decreased immunity. The Wistar-Kyoto rat (WKY is a strain in which the hypothalamic-pituitary-adrenal axis is overactivated. To determine whether chronic stress induces changes in corticosterone levels and splenic lymphoid tissue, 9-week-old male rats were subject to restraint stress (3 h daily, chemical stress (hydrocortisone treatment, 50 mg/Kg weight, mixed stress (restraint plus hydrocortisone, or control treatment (without stress for 1, 4, and 7 weeks. The serum corticosterone levels by RIA and spleens morphology were analyzed. Corticosterone levels as did the structure, size of the follicles and morphology of the parenchyma (increase in red pulp in the spleen, varied depending on time and type of stressor. These changes indicate that chronic stress alters the immune response in the spleen in WKY rats by inducing morphological changes, explaining in part the impaired immunity that develops in organisms that are exposed to chronic stress.

  13. Persistent Comorbidities in Cushing’s Syndrome after Endocrine Cure

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    Eugenia Resmini

    2014-01-01

    Full Text Available It was assumed that resolution of hypercortisolism in Cushing syndrome (CS was followed by normalization of morbidity; however, in the last decade evidence is accumulating that patients with cured CS still have increased morbidity and mortality after the biochemical control of hypercortisolism. Patients with CS have an increased cardiovascular and metabolic risk and persistent accumulation of central fat, with an unfavorable adipokine profile, not only during the active phase of the disease but also long after biochemical remission. Clinical management should be particularly careful in identifying global cardiovascular risk, as a primary goal during the followup of these patients, aimed at improving global vascular morbidity. Moreover bone mass is reduced not only due to the endogenous hypercortisolism but also due to duration and dose of exogenous glucocorticoid (GC replacement therapy after surgery. Thus, therapy in operated patients with inhibition of the hypothalamic-pituitary-adrenal axis should be reduced to the lowest dose and duration possible. Specific treatments should be considered in patients with decreased bone mass, aimed at reducing the increased fracture incidence. Finally, cognitive and health related quality of life impairments, described in active disease, are still abnormal after endocrine cure. Thus, residual morbidity persists in cured CS, suggesting irreversibility of GC-induced phenomena, typical of chronic hypercortisolism.

  14. Anxiety disorders.

    Science.gov (United States)

    Craske, Michelle G; Stein, Murray B; Eley, Thalia C; Milad, Mohammed R; Holmes, Andrew; Rapee, Ronald M; Wittchen, Hans-Ulrich

    2017-05-04

    Anxiety disorders constitute the largest group of mental disorders in most western societies and are a leading cause of disability. The essential features of anxiety disorders are excessive and enduring fear, anxiety or avoidance of perceived threats, and can also include panic attacks. Although the neurobiology of individual anxiety disorders is largely unknown, some generalizations have been identified for most disorders, such as alterations in the limbic system, dysfunction of the hypothalamic-pituitary-adrenal axis and genetic factors. In addition, general risk factors for anxiety disorders include female sex and a family history of anxiety, although disorder-specific risk factors have also been identified. The diagnostic criteria for anxiety disorders varies for the individual disorders, but are generally similar across the two most common classification systems: the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and the International Classification of Diseases, Tenth Edition (ICD-10). Despite their public health significance, the vast majority of anxiety disorders remain undetected and untreated by health care systems, even in economically advanced countries. If untreated, these disorders are usually chronic with waxing and waning symptoms. Impairments associated with anxiety disorders range from limitations in role functioning to severe disabilities, such as the patient being unable to leave their home.

  15. Cortisol response to social stress in parentally bereaved youth.

    Science.gov (United States)

    Dietz, Laura J; Stoyak, Samuel; Melhem, Nadine; Porta, Giovanna; Matthews, Karen A; Walker Payne, Monica; Brent, David A

    2013-02-15

    Parental bereavement is associated with increased risk for psychiatric illness and functional impairment in youth. Dysregulated hypothalamic-pituitary-adrenal (HPA) axis functioning may be one pathway through which bereaved children experience increased risk for poor outcomes. However, few studies have prospectively examined the association between parental bereavement and cortisol response while accounting for psychiatric disorders in both youth and their caregivers. One-hundred and eighty-one bereaved and nonbereaved offspring and their caregivers were assessed at multiple time points over a 5-year period after parental death. Offspring participated in an adaptation of the Trier Social Stress Task (TSST), and salivary cortisol samples were collected before and after exposure to social stressors. Mixed models for repeated measures were used to analyze the effects of bereavement status, psychiatric disorder in both offspring and caregiver, and demographic indices on trajectories of cortisol response. After controlling for demographic variables and offspring depression, bereaved offspring demonstrated significantly different trajectories of cortisol response compared with nonbereaved offspring, characterized by higher total cortisol output and an absence of cortisol reactivity to acute social stress. Within the bereaved group, offspring of parents who died by sudden natural death demonstrated significant cortisol reactivity to social stress compared with offspring whose parents died by suicide, who demonstrated more blunted trajectory of cortisol response. Parentally bereaved youth demonstrate higher cortisol output than nonbereaved youth but are less able to mount an acute response in the face of social stressors. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  16. A pilot study employing Dehydroepiandrosterone (DHEA) in the treatment of chronic fatigue syndrome.

    Science.gov (United States)

    Himmel, P B; Seligman, T M

    1999-04-01

    Patients with chronic fatigue syndrome (CFS) frequently associate the disease onset with a period of high physical and/or emotional stress. Alterations in hypothalamic-pituitary adrenal axis (HPA) function have been demonstrated. Although Cortisol production in patients with CFS has proven to be low, Dehydroepiandrosterone (DHEA) production has not been measured. DHEA output may be altered in this population. The purpose of this uncontrolled, prospective, 6 month study of 23 white women, ages 35-55 was to identify CFS patients with suboptimal serum levels of DHEA-sulphate (DHEA-S), defined as DHEA-S DHEA. DHEA-S levels were re-measured after 4-6 weeks of oral DHEA therapy (25 mg). If DHEA-S remained DHEA was given. Physical and psychological impairment and disability status were measured by the MHAQII before DHEA intervention and at 3-month intervals. Of initially screened patients with CFS, 76% (116 of 153) were ages 35-55, and 89% (103 of 116) had suboptimal (DHEA-S.Supplementation with DHEA to CFS patients lead to a significant reduction in the symptoms of CFS: pain (improved by 18%, p = 0.035), fatigue (decreased by 21%, p = 0.009)), activities of daily living (improved by 8.5%, p = 0.058), helplessness (decreased by 11%, p = 0.015), anxiety (decreased by 35%, p memory (improved by 17%, p DHEA to this population in a controlled setting.

  17. Two diagnoses become one? Rare case report of anorexia nervosa and Cushing’s syndrome

    Directory of Open Access Journals (Sweden)

    Sawicka N

    2013-03-01

    Full Text Available Nadia Sawicka,* Maria Gryczyńska,* Jerzy Sowiński, Monika Tamborska-Zedlewska, Marek Ruchała Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland*These authors contributed equally to this workAbstract: Hypothalamic-pituitary-adrenal axis impairment in anorexia nervosa is marked by hypercortisolemia, and psychiatric disorders occur in the majority of patients with Cushing’s syndrome. Here we report a patient diagnosed with anorexia nervosa who also developed Cushing’s syndrome. A 26-year-old female had been treated for anorexia nervosa since she was 17 years old, and also developed depression and paranoid schizophrenia. She was admitted to the Department of Endocrinology, Metabolism, and Internal Medicine with a preliminary diagnosis of Cushing’s syndrome. Computed tomography revealed a 27 mm left adrenal tumor, and she underwent laparoscopic adrenalectomy. She was admitted to hospital 6 months after this procedure, at which time she did not report any eating or mood disorder. This is a rare case report of a patient with anorexia nervosa in whom Cushing’s syndrome was subsequently diagnosed. Diagnostic difficulties were caused by the signs and symptoms presenting in the course of both disorders, ie, hypercortisolemia, osteoporosis, secondary amenorrhea, striae, hypokalemia, muscle weakness, and depression.Keywords: anorexia nervosa, Cushing’s syndrome, adrenalectomy, osteoporosis

  18. Aggression and anxiety: social context and neurobiological links

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    Inga D Neumann

    2010-03-01

    Full Text Available Psychopathologies such as anxiety- and depression-related disorders are often characterized by impaired social behaviours including excessive aggression and violence. Excessive aggression and violence likely develop as a consequence of generally disturbed emotional regulation, such as abnormally high or low levels of anxiety. This suggests an overlap between brain circuitries and neurochemical systems regulating aggression and anxiety. In this review, we will discuss different forms of male aggression, rodent models of excessive aggression, and neurobiological mechanisms underlying male aggression in the context of anxiety. We will summarize our attempts to establish an animal model of high and abnormal aggression using rats selected for high (HAB versus low (LAB anxiety-related behaviour. Briefly, male LAB rats and, to a lesser extent, male HAB rats show high and abnormal forms of aggression compared with non-selected (NAB rats, making them a suitable animal model for studying excessive aggression in the context of extremes in innate anxiety. In addition, we will discuss differences in the activity of the hypothalamic-pituitary-adrenal axis, brain arginine vasopressin, and the serotonin systems, among others, which contribute to the distinct behavioural phenotypes related to aggression and anxiety. Further investigation of the neurobiological systems in animals with distinct anxiety phenotypes might provide valuable information about the link between excessive aggression and disturbed emotional regulation, which is essential for understanding the social and emotional deficits that are characteristic of many human psychiatric disorders.

  19. Anxiety mediates the effect of acute stress on working memory performance when cortisol levels are high: a moderated mediation analysis.

    Science.gov (United States)

    Hood, Anna; Pulvers, Kim; Spady, Thomas J; Kliebenstein, Alexa; Bachand, Jennifer

    2015-01-01

    Anxiety is an aversive emotional state characterized by perceived uncontrollability and hypervigilance to threat that can frequently cause disruptions in higher-order cognitive processes like working memory. The attentional control theory (ACT) predicts that anxiety negatively affects the working memory system. This study tested the association between anxiety and working memory after the addition of stress and measured the glucocorticoid, cortisol. To better understand this relationship, we utilized a moderated mediation model. Undergraduate students from a public university (N = 103) self-reported their anxiety levels. Participants first completed a short-term memory test. During and after a forehead cold pressor task (stress vs. control procedure) participants completed a working memory test. Salivary cortisol was taken at baseline and after the last working memory test. Overall, acute stress had no effect on working memory. However, we found that anxiety levels mediated the influence of condition (stressed vs. control) on working memory, but only among those individuals who had high cortisol levels after exposure to acute stress, supporting a moderated mediation model. These results imply that activation of the hypothalamic-pituitary-adrenal axis was necessary for working memory impairment in anxious individuals. These results provide support for the ACT.

  20. Emotional Regulation and Depression: A Potential Mediator between Heart and Mind

    Directory of Open Access Journals (Sweden)

    Angelo Compare

    2014-01-01

    Full Text Available A narrative review of the major evidence concerning the relationship between emotional regulation and depression was conducted. The literature demonstrates a mediating role of emotional regulation in the development of depression and physical illness. Literature suggests in fact that the employment of adaptive emotional regulation strategies (e.g., reappraisal causes a reduction of stress-elicited emotions leading to physical disorders. Conversely, dysfunctional emotional regulation strategies and, in particular, rumination and emotion suppression appear to be influential in the pathogenesis of depression and physiological disease. More specifically, the evidence suggests that depression and rumination affect both cognitive (e.g., impaired ability to process negative information and neurobiological mechanisms (e.g., hypothalamic pituitary adrenal axis overactivation and higher rates of cortisol production. Understanding the factors that govern the variety of health outcomes that different people experience following exposure to stress has important implications for the development of effective emotion-regulation interventional approaches (e.g., mindfulness-based therapy, emotion-focused therapy, and emotion regulation therapy.

  1. Chronic Stress Induces Structural Alterations in Splenic Lymphoid Tissue That Are Associated with Changes in Corticosterone Levels in Wistar-Kyoto Rats

    Science.gov (United States)

    Hernandez, María Eugenia; Martinez-Mota, Lucia; Salinas, Citlaltepetl; Marquez-Velasco, Ricardo; Hernandez-Chan, Nancy G.; Morales-Montor, Jorge; Pérez-Tapia, Mayra; Streber, María L.; Granados-Camacho, Ivonne; Becerril, Enrique; Javier, Baquera-Heredia; Pavón, Lenin

    2013-01-01

    Major depressive disorder patients present chronic stress and decreased immunity. The Wistar-Kyoto rat (WKY) is a strain in which the hypothalamic-pituitary-adrenal axis is overactivated. To determine whether chronic stress induces changes in corticosterone levels and splenic lymphoid tissue, 9-week-old male rats were subject to restraint stress (3 h daily), chemical stress (hydrocortisone treatment, 50 mg/Kg weight), mixed stress (restraint plus hydrocortisone), or control treatment (without stress) for 1, 4, and 7 weeks. The serum corticosterone levels by RIA and spleens morphology were analyzed. Corticosterone levels as did the structure, size of the follicles and morphology of the parenchyma (increase in red pulp) in the spleen, varied depending on time and type of stressor. These changes indicate that chronic stress alters the immune response in the spleen in WKY rats by inducing morphological changes, explaining in part the impaired immunity that develops in organisms that are exposed to chronic stress. PMID:23533999

  2. A current status of adaptogens: natural remedy to stress

    Directory of Open Access Journals (Sweden)

    Pawar Vinod S

    2012-05-01

    Full Text Available Stress is a normal part of everyday life but it is important to be able to use tools for its management otherwise chronic stress, if left untreated, can lead to a variety of stress related illnesses including hypertension, heart disease, anxiety, depression, memory impairment and chronic fatigue syndrome. The aim of this literature review is to summarize and critically analyze research conducted on the adaptogenic herbs. The aim of this review article is to assess the level of scientific evidence presented by the adaptogens from natural origin by different screening methods and to provide a rationale at the molecular level. Strong scientific evidence is available in relation with the molecular mechanisms associated with their stress- protective activity against acute and chronic paradigms. The beneficial stress- protective effect of adaptogens is in relation with regulation of homeostasis via several mechanisms of action associated with the hypothalamic- pituitary-adrenal axis and the control of key stress mediators and biochemical markers such as nitric oxide (NO, cortisol, cholesterol, triglycerides, glucose etc. Good scientific evidence has been documented with active secondary metabolites present in adaptogens.

  3. Gonadal and Adrenal Abnormalities in Drug Users: Cause or Consequence of Drug Use Behavior and Poor Health Outcomes

    Directory of Open Access Journals (Sweden)

    Todd T. Brown

    2006-01-01

    Full Text Available Opiates and cocaine both have effects on adrenal and gonadal function. Opiates suppress the hypothalamic-pituitary adrenal (HPA axis, whereas cocaine leads to HPA activation. Opiates also cause gonadal dysfunction in both men and women. During withdrawal from opiates and cocaine, the HPA axis is activated which may reinforce relapse behavior. This review describes these hormonal effects and explores the potential consequences, including the effects on mood cognition and cardiovascular risk. Modification of the drug-induced hormonal dysfunction may represent a treatment strategy for drug rehabilitation.

  4. GENETIC DEFECTS IN THE GROWTH HORMONE-IGF-I AXIS CAUSING GROWTH HORMONE INSENSITIVITY AND IMPAIRED LINEAR GROWTH

    Directory of Open Access Journals (Sweden)

    Martin O. Savage

    2011-12-01

    Full Text Available Human genetic defects in the growth hormone (GH –IGF-I axis affecting the IGF system present with growth failure as their principal clinical feature. This is usually associated with GH insensitivity (GHI presenting in childhood as severe or mild short stature. Dysmorphic features and metabolic abnormalities may also be present. The field of GHI due to mutations affecting GH action has evolved radidly since the first description of the extreme phenotype related to homozygous GH receptor (GHR mutations in 1966. A continuum of genetic, phenotypic, and biochemical abnormalities can be defined associated with clinically relevant defects in linear growth. The mechanisms of the GH–IGF-I axis in the regulation of normal human growth is discussed followed by descriptions of mutations in GHR, STAT5B, IGF-I, IGFALS, IGF1R and GH1 defects causing bioinactive GH or anti-GH antibodies. These GH-IGF-I axis defects are associated with a range of clinical, and hormonal characteristics. An up-dated approach to the clinical assessment of the patient with GHI focussing on investigation of the GH–IGF-I axis and relevant molecular studies contributing to the identification of causative genetic defects is also discussed.

  5. Stress, genetics and epigenetic effects on the neurobiology of suicidal behavior and depression

    Science.gov (United States)

    Mann, J. J.; Currier, D. M.

    2010-01-01

    Alterations in a number of neurobiological systems have been associated with suicidal behavior including the serotonergic and noradrenergic systems and the hypothalamic-pituitary-adrenal axis. Altered functioning of these systems may stem from both genetic and developmental causes. Adversity in early-life has developmental consequences on these systems that persist into adulthood. Genetic differences may also contribute to alterations in functioning of neurobiological systems. Moreover, the interaction of early- life experiences of adversity and genetic vulnerability is increasing thought to play a role, including via epigenetic mechanisms. PMID:20451357

  6. Sensitization of restraint-induced corticosterone secretion after chronic restraint in rats: Involvement of 5-HT7 receptors

    OpenAIRE

    García-Iglesias, Brenda B.; Mendoza-Garrido, María E; Gutiérrez-Ospina, Gabriel; Rangel-Barajas, Claudia; Noyola-Díaz, Martha; Terrón, José A.

    2013-01-01

    Serotonin (5-HT) modulates the hypothalamic-pituitary-adrenal (HPA) axis response to stress. We examined the effect of chronic restraint stress (CRS; 20 min/day) as compared to control (CTRL) conditions for 14 days, on: 1) restraint-induced ACTH and corticosterone (CORT) secretion in rats pretreated with vehicle or SB-656104 (a 5-HT7 receptor antagonist); 2) 5-HT7 receptor-like immunoreactivity (5-HT7-LI) and protein in the hypothalamic paraventricular nucleus (PVN) and adrenal glands (AG); 3...

  7. Expression of hippocampal corticosteroid receptors, as well as corticotrophin-releasing hormone and vasopressin in the hypothalamic paraventricular nucleus, in fornix transected rats

    Institute of Scientific and Technical Information of China (English)

    Fang Han; Hong Liu; Yanhui Zhang; Yuxiu Shi

    2009-01-01

    BACKGROUND: The hippocampus regulates the hypothalamic-pituitary-adrenal axis through negative feedback. The hypothalamic paraventdcular nucleus receives neuronal input from the hippocampus via the fornix.OBJECTIVE: To explore whether the negative feedback effect of the hippocampus on the hypothalamic-pituitary-adrenal axis is contributed to the inhibitory effect of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) in the hippocampus on the paraventricular nucleus via the fomix.DESIGN, TIME AND SETTING: Randomized, controlled, animal experiment. The study was performed at the Department of Histology and Embryology, China Medical University between September 2006 and September 2008.MATERIALS: Rabbit anti-rat anti-MR and rabbit anti-rat anti-GR antibodies were purchased from Santa Cruz Biotechnology, USA. Rabbit anti-rat anti-corticotrophin releasing hormone (CRH) and rabbit anti-rat anti-arginine vasopressin antibodies were purchased from Wuhan Boster.METHODS: A total of 90 male, Wistar rats were randomly divided into model and sham-surgery groups (n=45). Fornix transection was performed in the model group, while the sham-surgery group underwent surgery, but no fornix transection.MAIN OUTCOME MEASURES: Immunohistochemistry was used to examine MR and GR expression in the hippocampus, as well as CRH and anti-arginine vasopressin in the paraventricular nucleus. Western blot was used to measure alterations in MR, GR, and CRH protein expression following fomix transection.RESULTS: Compared with the sham-surgery group, there were no obvious changes in MR and GR expression in the hippocampus, or CRH and anti-arginine vasopressin expression in the paraventricular nucleus within 4 days of fornix transection. However, after 7-10 days, significantly decreased MR and GR expression in the hippocampus, and increased CRH and anti-arginine vasopressin expression in the paraventricular nucleus were observed (P < 0.05-0.01).CONCLUSION: Negative feedback from the

  8. Does intensity or youth affect the neurobiological effect of exercise on major depressive disorder?

    Science.gov (United States)

    Budde, Henning; Velasques, Bruna; Ribeiro, Pedro; Machado, Sergio; Emeljanovas, Arunas; Kamandulis, Sigitas; Skurvydas, Albertas; Wegner, Mirko

    2016-09-28

    The purpose of this commentary is to discuss the different neurobiological effects of exercise on major depressive disorder (MDD) in children and adolescents and to provide additional explanations to this well written systematic review. This commentary highlights the effects of exercise on the hypothalamic-pituitary-adrenal (HPA) axis, which plays a crucial role in MDD. We address the questions of whether age and different exercise intensities may provide additional information on the neurobiological effects of acute or chronic exercise on MDD. Previous findings clearly suggest that the etiology of MDD is complex and multifaceted, involving numerous neurobiological systems, which are additionally influenced by these two factors.

  9. Atrial natriuretic peptide and feeding activity patterns in rats

    Directory of Open Access Journals (Sweden)

    Oliveira M.H.A.

    1997-01-01

    Full Text Available This review presents historical data about atrial natriuretic peptide (ANP from its discovery as an atrial natriuretic factor (ANF to its role as an atrial natriuretic hormone (ANH. As a hormone, ANP can interact with the hypothalamic-pituitary-adrenal axis (HPA-A and is related to feeding activity patterns in the rat. Food restriction proved to be an interesting model to investigate this relationship. The role of ANP must be understood within a context of peripheral and central interactions involving different peptides and pathways

  10. [Psychosocial aspects of preeclampsia].

    Science.gov (United States)

    Szita, Bernadett; Baji, Ildikó; Rigó, János

    2015-12-13

    Distress conditions during pregnancy may contribute to the development of preeclampsia by altering functions of the neuroendocrine and immune systems, e.g. activation of the hypothalamic-pituitary-adrenal axis and increase in plasma proinflammatory cytokines. Preeclampsia may also precipitate mental health problems due to long-term hospitalization or unpredictable and uncontrollable events such as preterm labor and newborn complications. Besides, preeclampsia may induce persistent neurocognitive complaints with a negative impact on patients' quality of life. As growing evidence indicates that poor maternal mental health has an adverse effect on pregnancy outcome and fetal development, psychosocial interventions may be beneficial for women with preeclampsia.

  11. The neurodevelopmental origins of suicidal behavior.

    Science.gov (United States)

    Turecki, Gustavo; Ernst, Carl; Jollant, Fabrice; Labonté, Benoit; Mechawar, Naguib

    2012-01-01

    Suicide and related behaviors are complex phenomena associated with different risk factors. Although most individuals who display suicidal behavior do not have a history of early-life adversity, a significant minority does. Recent animal and human data have suggested that early-life adversity leads to epigenetic regulation of genes involved in stress-response systems. Here, we review this evidence and suggest that early-life adversity increases risk of suicide in susceptible individuals by influencing the development of stable emotional, behavioral and cognitive phenotypes that are likely to result from the epigenetic regulation of the hypothalamic-pituitary-adrenal axis and other systems involved in responses to stress.

  12. Stress og hjerte-kar-sygdom

    DEFF Research Database (Denmark)

    Ebstrup, Jeanette Frost; Jørgensen, Torben

    2012-01-01

    Risk factors of cardiovascular disease (CVD) have been studied intensely since the 1950s. Results on stress as a risk factor for CVD have been inconsistent, but mainly positive. The risk is mediated through lifestyle, but more direct physiological mechanisms (e.g. autonomous nervous system...... and hypothalamic-pituitary-adrenal axis) are also found. Personality and general coping resources influence stress-appraisal, stress-coping and stress-response. Future studies should integrate stress as a cause (stressor), as a subjective reaction (perception), and as a physiological reaction in the same...

  13. The aphrodisiac and adaptogenic properties of ginseng.

    Science.gov (United States)

    Nocerino, E; Amato, M; Izzo, A A

    2000-08-01

    Ginseng is the root of the perennial herbs of Panax quinquefolium and Panax ginseng which contain a series of tetracyclic triterpenoid saponins (ginsenosides) as active ingredients. It is considered a tonic or adaptogenic that enhances physical performance (including sexual), promotes vitality and increases resistance to stress and ageing. The adaptogenic properties of ginseng are believed to be due to its effects on hypothalamic-pituitary-adrenal axis, resulting in elevated plasma corticotropin and corticosteroids levels. When used appropriately, ginseng appears to be safe. Nevertheless, documented side effects include hypertension, diarrhoea, restlessness, mastalgia and vaginal bleeding.

  14. Getting under the skin: Report from the International Psoriasis Council workshop on the role of stress in psoriasis

    Directory of Open Access Journals (Sweden)

    Julia eSchwartz

    2016-02-01

    Full Text Available Psoriasis is a chronic inflammatory skin condition with significant physical and psychosocial comorbidity. A workshop of leading experts in dermatology and psychology with the purpose of better understanding the current role of psychological comorbidities in psoriasis was held by the International Psoriasis Council in November 2013. The role of stress reactivity with a focus on the hypothalamic-pituitary-adrenal axis was emphasized. While cognitive behavioral therapy remains the most extensively studied and successful treatment strategy in patients with psoriasis and various psychological comorbidities, new and innovative interventions such as online-based therapies have recently emerged. Strategies and recommendations towards approaching psychological comorbidities are discussed.

  15. Carbohydrate-based drugs in the treatment of epilepsy, depression and other affective disorders.

    Science.gov (United States)

    Talisman, Ian Jamie; Marzabadi, Cecilia H

    2008-01-01

    Mental illness affects a quarter of the US population. Recently, it has been shown that new, carbohydrate-based drugs hold promise in the treatment of central nervous system (CNS) disorders. A variety of ways in which drugs of this sort may reduce the symptoms of epilepsy, depression and other affective disorders have been proposed, including: targeting the immune system, disrupting glycolysis, acting at different sites in the hypothalamic-pituitary-adrenal (HPA) axis, and targeting specific biochemical pathways such as the inositol pathway. In the present review, the structure-activity relationships (SARs) of a wide variety of CNS-active carbohydrates are presented.

  16. Stress og hjerte-kar-sygdom

    DEFF Research Database (Denmark)

    Ebstrup, Jeanette Frost; Jørgensen, Torben

    2012-01-01

    Risk factors of cardiovascular disease (CVD) have been studied intensely since the 1950s. Results on stress as a risk factor for CVD have been inconsistent, but mainly positive. The risk is mediated through lifestyle, but more direct physiological mechanisms (e.g. autonomous nervous system...... and hypothalamic-pituitary-adrenal axis) are also found. Personality and general coping resources influence stress-appraisal, stress-coping and stress-response. Future studies should integrate stress as a cause (stressor), as a subjective reaction (perception), and as a physiological reaction in the same...

  17. Sex and gender in psychoneuroimmunology research: past, present and future.

    Science.gov (United States)

    Darnall, Beth D; Suarez, Edward C

    2009-07-01

    To date, research suggests that sex and gender impact pathways central to the foci of psychoneuroimmunology (PNI). This review provides a historical perspective on the evolution of sex and gender in psychoneuroimmunology research. Gender and sexually dimorphic pathways may have synergistic effects on health differences in men and women. We provide an overview of the literature of sex and gender differences in brain structure and function, sex steroids, gender role identification, hypothalamic-pituitary-adrenal axis function, genetics, immunology and cytokine response. Specific examples shed light on the importance of attending to sex and gender methodology in PNI research and recommendations are provided.

  18. Posttraumatic stress and immune dissonance

    Institute of Scientific and Technical Information of China (English)

    JIANG Jian-xin

    2008-01-01

    @@ Stress or neuroendocrine response usually occurs soon after trauma, which is central to the maintenance of posttraumatic homeostasis. Immune inflammatory response has been recognized to be a key element both in the pathogenesis of post-traumatic complications and in tissue repair. Despite the existence of multiple and intricate interconnected neuroendocrine pathways, the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system have been considered to be the most important in trauma. Although the short-term and appropriate activation of these

  19. Impaired genome maintenance suppresses the growth hormone--insulin-like growth factor 1 axis in mice with Cockayne syndrome.

    Directory of Open Access Journals (Sweden)

    Ingrid van der Pluijm

    2007-01-01

    Full Text Available Cockayne syndrome (CS is a photosensitive, DNA repair disorder associated with progeria that is caused by a defect in the transcription-coupled repair subpathway of nucleotide excision repair (NER. Here, complete inactivation of NER in Csb(m/m/Xpa(-/- mutants causes a phenotype that reliably mimics the human progeroid CS syndrome. Newborn Csb(m/m/Xpa(-/- mice display attenuated growth, progressive neurological dysfunction, retinal degeneration, cachexia, kyphosis, and die before weaning. Mouse liver transcriptome analysis and several physiological endpoints revealed systemic suppression of the growth hormone/insulin-like growth factor 1 (GH/IGF1 somatotroph axis and oxidative metabolism, increased antioxidant responses, and hypoglycemia together with hepatic glycogen and fat accumulation. Broad genome-wide parallels between Csb(m/m/Xpa(-/- and naturally aged mouse liver transcriptomes suggested that these changes are intrinsic to natural ageing and the DNA repair-deficient mice. Importantly, wild-type mice exposed to a low dose of chronic genotoxic stress recapitulated this response, thereby pointing to a novel link between genome instability and the age-related decline of the somatotroph axis.

  20. Normal sweat secretion despite impaired growth hormone-insulin-like growth factor-I axis in obese subjects

    DEFF Research Database (Denmark)

    Rasmussen, Michael Højby; Juul, Anders; Main, Katharina M

    2011-01-01

    and after weight loss. Sixteen severely obese women (BMI, 40.6 ± 1.1 kg/m(2)) were investigated before and after a diet-induced weight loss. Sixteen age-matched nonobese women served as controls. The obese subjects presented the characteristic decreased GH release, hyperinsulinaemia, increased FFA levels......, and impaired insulin sensitivity, which all were normalised after diet-induced weight loss of 30 ± 5 kg. Sweat secretion rates were similar comparing obese and nonobese subjects (78 ± 10 versus 82 ± 9 mg/30 minutes) and sweat secretion did not change after a diet-induced weight loss in obese subjects. We...... conclude that although obese subjects have markedly reduced GH release and impaired IGF-I levels, sweat secretion rate is found to be normal....

  1. HPA axis and vagus nervous function are involved in impaired insulin secretion of MSG-obese rats.

    Science.gov (United States)

    Miranda, Rosiane A; Torrezan, Rosana; de Oliveira, Júlio C; Barella, Luiz F; da Silva Franco, Claudinéia C; Lisboa, Patrícia C; Moura, Egberto G; Mathias, Paulo C F

    2016-07-01

    Neuroendocrine dysfunctions such as the hyperactivity of the vagus nerve and hypothalamus-pituitary-adrenal (HPA) axis greatly contribute to obesity and hyperinsulinemia; however, little is known about these dysfunctions in the pancreatic β-cells of obese individuals. We used a hypothalamic-obesity model obtained by neonatal treatment with monosodium l-glutamate (MSG) to induce obesity. To assess the role of the HPA axis and vagal tonus in the genesis of hypercorticosteronemia and hyperinsulinemia in an adult MSG-obese rat model, bilateral adrenalectomy (ADX) and subdiaphragmatic vagotomy (VAG) alone or combined surgeries (ADX-VAG) were performed. To study glucose-induced insulin secretion (GIIS) and the cholinergic insulinotropic process, pancreatic islets were incubated with different glucose concentrations with or without oxotremorine-M, a selective agonist of the M3 muscarinic acetylcholine receptor (M3AChR) subtype. Protein expression of M3AChR in pancreatic islets, corticosteronemia, and vagus nerve activity was also evaluated. Surgeries reduced 80% of the body weight gain. Fasting glucose and insulin were reduced both by ADX and ADX-VAG, whereas VAG was only associated with hyperglycemia. The serum insulin post-glucose stimulation was lower in all animals that underwent an operation. Vagal activity was decreased by 50% in ADX rats. In the highest glucose concentration, both surgeries reduced GIIS by 50%, whereas ADX-VAG decreased by 70%. Additionally, M3AChR activity was recovered by the individual surgeries. M3AChR protein expression was reduced by ADX. Both the adrenal gland and vagus nerve contribute to the hyperinsulinemia in the MSG model, although adrenal is more crucial as it appears to modulate parasympathetic activity and M3AChR expression in obesity.

  2. Chronic Psychological Stress Accelerates Vascular Senescence and Impairs Ischemia-Induced Neovascularization: The Role of Dipeptidyl Peptidase-4/Glucagon-Like Peptide-1-Adiponectin Axis.

    Science.gov (United States)

    Piao, Limei; Zhao, Guangxian; Zhu, Enbo; Inoue, Aiko; Shibata, Rei; Lei, Yanna; Hu, Lina; Yu, Chenglin; Yang, Guang; Wu, Hongxian; Xu, Wenhu; Okumura, Kenji; Ouchi, Noriyuki; Murohara, Toyoaki; Kuzuya, Masafumi; Cheng, Xian Wu

    2017-09-28

    Exposure to psychosocial stress is a risk factor for cardiovascular disease, including vascular aging and regeneration. Given that dipeptidyl peptidase-4 (DPP4) regulates several intracellular signaling pathways associated with the glucagon-like peptide-1 (GLP-1) metabolism, we investigated the role of DPP4/GLP-1 axis in vascular senescence and ischemia-induced neovascularization in mice under chronic stress, with a special focus on adiponectin -mediated peroxisome proliferator activated receptor-γ/its co-activator 1α (PGC-1α) activation. Seven-week-old mice subjected to restraint stress for 4 weeks underwent ischemic surgery and were kept under immobilization stress conditions. Mice that underwent ischemic surgery alone served as controls. We demonstrated that stress impaired the recovery of the ischemic/normal blood-flow ratio throughout the follow-up period and capillary formation. On postoperative day 4, stressed mice showed the following: increased levels of plasma and ischemic muscle DPP4 and decreased levels of GLP-1 and adiponectin in plasma and phospho-AMP-activated protein kinase α (p-AMPKα), vascular endothelial growth factor, peroxisome proliferator activated receptor-γ, PGC-1α, and Sirt1 proteins and insulin receptor 1 and glucose transporter 4 genes in the ischemic tissues, vessels, and/or adipose tissues and numbers of circulating endothelial CD31(+)/c-Kit(+) progenitor cells. Chronic stress accelerated aortic senescence and impaired aortic endothelial sprouting. DPP4 inhibition and GLP-1 receptor activation improved these changes; these benefits were abrogated by adiponectin blocking and genetic depletion. These results indicate that the DPP4/GLP-1-adiponectin axis is a novel therapeutic target for the treatment of vascular aging and cardiovascular disease under chronic stress conditions. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  3. AC1MMYR2 impairs high dose paclitaxel-induced tumor metastasis by targeting miR-21/CDK5 axis.

    Science.gov (United States)

    Ren, Yu; Zhou, Xuan; Yang, Juan-Juan; Liu, Xia; Zhao, Xiao-hui; Wang, Qi-xue; Han, Lei; Song, Xin; Zhu, Zhi-yan; Tian, Wei-ping; Zhang, Lun; Mei, Mei; Kang, Chun-sheng

    2015-07-01

    Paclitaxel (taxol) is a widely used chemo-drug for many solid tumors, while continual taxol treatment is revealed to stimulate tumor dissemination. We previously found that a small molecule inhibitor of miR-21, termed AC1MMYR2, had the potential to impair tumorigenesis and metastasis. The aim of this study was to investigate whether combining AC1MMYR2 with taxol could be explored as a means to limit tumor metastasis. Here we showed that abnormal activation of miR-21/CDK5 axis was associated with breast cancer lymph node metastasis, which was also contribute to high dose taxol-induced invasion and epithelial mesenchymal transition (EMT) in both breast cancer cell line MDA-MB-231 and glioblastoma cell line U87VIII. AC1MMYR2 attenuated CDK5 activity by functional targeting CDK5RAP1, CDK5 activator p39 and target p-FAK(ser732). A series of in vitro assays indicated that treatment of AC1MMYR2 combined with taxol suppressed tumor migration and invasion ability in both MDA-MB-231 and U87VIII cell. More importantly, combination therapy impaired high-dose taxol induced invadopodia, and EMT markers including β-catenin, E-cadherin and vimentin. Strikingly, a significant reduction of lung metastasis in mice was observed in the AC1MMYR2 plus taxol treatment. Taken together, our work demonstrated that AC1MMYR2 appeared to be a promising strategy in combating taxol induced cancer metastasis by targeting miR-21/CDK5 axis, which highlighted the potential for development of therapeutic modalities for better clinic taxol application.

  4. Treatment with an SSRI antidepressant restores hippocampo-hypothalamic corticosteroid feedback and reverses insulin resistance in low-birth-weight rats.

    Science.gov (United States)

    Buhl, Esben S; Jensen, Thomas Korgaard; Jessen, Niels; Elfving, Betina; Buhl, Christian S; Kristiansen, Steen B; Pold, Rasmus; Solskov, Lasse; Schmitz, Ole; Wegener, Gregers; Lund, Sten; Petersen, Kitt Falck

    2010-05-01

    Low birth weight (LBW) is associated with type 2 diabetes and depression, which may be related to prenatal stress and insulin resistance as a result of chronic hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. We examined whether treatment with a selective serotonin reuptake inhibitor [escitalopram (ESC)] could downregulate HPA axis activity and restore insulin sensitivity in LBW rats. After 4-5 wk of treatment, ESC-exposed LBW (SSRI-LBW) and saline-treated control and LBW rats (Cx and LBW) underwent an oral glucose tolerance test or a hyperinsulinemic euglycemic clamp to assess whole body insulin sensitivity. Hepatic phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression and red skeletal muscle PKB Ser(473) phosphorylation were used to assess tissue-specific insulin sensitivity. mRNA expression of the hypothalamic mineralocorticoid receptor was fivefold upregulated in LBW (P < 0.05 vs. Cx), accompanied by increased corticosterone release during restraint stress and total 24-h urinary excretion (P < 0.05 vs. Cx), whole body insulin resistance (P < 0.001 vs. Cx), and impaired insulin suppression of hepatic PEPCK mRNA expression (P < 0.05 vs. Cx). Additionally, there was a tendency for reduced red muscle PKB Ser(473) phosphorylation. The ESC treatment normalized corticosterone secretion (P < 0.05 vs. LBW), whole body insulin sensitivity (P < 0.01) as well as postprandial suppression of hepatic mRNA PEPCK expression (P < 0.05), and red muscle PKB Ser(473) phosphorylation (P < 0.01 vs. LBW). We conclude that these data suggest that the insulin resistance and chronic HPA axis hyperactivity in LBW rats can be reversed by treatment with an ESC, which downregulates HPA axis activity, lowers glucocorticoid exposure, and restores insulin sensitivity in LBW rats.

  5. Cannabinoids and traumatic stress modulation of contextual fear extinction and GR expression in the amygdala-hippocampal-prefrontal circuit.

    Science.gov (United States)

    Ganon-Elazar, Eti; Akirav, Irit

    2013-09-01

    Considerable evidence suggests that cannabinoids modulate the behavioral and physiological response to stressful events. We have recently shown that activating the cannabinoid system using the CB1/CB2 receptor agonist WIN55,212-2 (WIN) in proximity to exposure to single-prolonged stress (SPS), a rat model of emotional trauma, prevented the stress-induced enhancement of acoustic startle response, the impairment in avoidance extinction and the enhanced negative feedback on the hypothalamic-pituitary-adrenal (HPA) axis (Ganon-Elazar and Akirav, 2012). Some of the effects were found to be mediated by CB1 receptors in the basolateral amygdala (BLA). Here we examined whether cannabinoid receptor activation in a putative brain circuit that includes the BLA, hippocampus and prefrontal cortex (PFC), could prevent the effects of traumatic stress on contextual fear extinction and alterations in glucocorticoid receptor (GR) protein levels. We found that: (i) SPS impaired contextual fear extinction tested one week after trauma exposure and that WIN prevented the stress-induced impairment of extinction when microinjected immediately after trauma exposure into the BLA or hippocampus (5 μg), but not when microinjected into the PFC, (ii) the ameliorating effects of WIN on contextual extinction were prevented by blocking GRs in the BLA and hippocampus, and (iii) SPS up regulated GRs in the BLA, PFC and hippocampus and systemic WIN administration (0.5 mg/kg) after trauma exposure normalized GR levels in the BLA and hippocampus, but not in the PFC. Cannabinoid receptor activation in the aftermath of trauma exposure may regulate the emotional response to the trauma and prevent stress-induced impairment of extinction and GR up regulation through the mediation of CB1 receptors in the BLA and hippocampus. Taken together, the findings suggest that the interaction between the cannabinoid and glucocorticoid systems is crucial in the modulation of emotional trauma.

  6. Diabetes and Insulin Injection Modalities: Effects on Hepatic and Hippocampal Expression of 11β-Hydroxysteroid Dehydrogenase Type 1 in Juvenile Diabetic Male Rats.

    Science.gov (United States)

    Rougeon, Véronica; Moisan, Marie-Pierre; Barthe, Nicole; Beauvieux, Marie-Christine; Helbling, Jean-Christophe; Pallet, Véronique; Marissal-Arvy, Nathalie; Barat, Pascal

    2017-01-01

    Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is often encountered in diabetes, leading to several clinical complications. Our recent results showing an elevated tetrahydrocortisol/tetrahydrocorticosterone ratio in morning urine of diabetic children compared to that of controls suggest an increased nocturnal activity of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in the former. We hypothesized that these observations could be explained by a reduced inhibition of hepatic 11β-HSD1 activity by exogenous insulin owing to its subcutaneous (SC) administration and absence of first hepatic passage. Additionally, we hypothesized that hippocampal 11β-HSD1 activity might also be impaired by diabetes. We therefore measured HPA axis activity and 11β-HSD1 expression and activity in liver and hippocampus in streptozotocin-induced diabetic juvenile rats treated with SC or intraperitoneal (IP) insulin. Plasma corticosterone levels were elevated in untreated diabetic rats during the resting phase and restored by both types of insulin treatment. The mRNA expression and activity of 11β-HSD1 were increased in the untreated diabetic group in liver. Although diabetes was controlled equally whatever the route of insulin administration, liver 11β-HSD1 gene expression and activity was decreased only in the IP group, suggesting that a first hepatic pass is needed for 11β-HSD1 hepatic inhibition. In hippocampus, 11β-HSD1 activity was elevated in the untreated diabetic group but restored by both types of insulin treatment. Thus, these data extend our findings in diabetic children by showing impairment of hippocampal 11β-HSD1 in diabetes and by demonstrating that IP is preferable to SC insulin administration to restore 11β-HSD1 activity in liver.

  7. Effects of cortisol on cognition in major depressive disorder, posttraumatic stress disorder and borderline personality disorder - 2014 Curt Richter Award Winner.

    Science.gov (United States)

    Wingenfeld, Katja; Wolf, Oliver T

    2015-01-01

    Stress hormones influence a wide range of cognitive functions, including memory performance and executive function. It is well established that glucocorticoids enhance memory consolidation but impair memory retrieval. While most of the effects have been attributed to glucocorticoid receptors (GR), the importance of mineralocorticoid receptors (MR) has been also emphasized. Dysfunctions in hypothalamic-pituitary-adrenal (HPA) axis have been reported for several mental disorders. While major depressive disorder (MDD) as well as borderline personality disorder (BPD) seem to be characterized by enhanced cortisol release in concert with a reduced feedback sensitivity of the HPA axis, in posttraumatic stress disorder (PTSD) a contrary picture has been reported. Despite the fact that altered GR function has been discussed for these disorders only very few studies have investigated the effects of glucocorticoids on cognitive performance in these patients so far. In a series of studies, we investigated the effects of glucocorticoids on cognition (i.e. declarative memory, working memory and response inhibition) in different mental disorders such as MDD, PTSD and BPD. While in patients with MDD cortisol administration failed to effect memory retrieval, patients with PTSD and BPD showed enhanced rather than impaired memory retrieval after cortisol administration. These results indicate an altered sensitivity to cortisol in these disorders. Results from one of our recent studies in the field of social cognition underline the importance of the MR. We found that emotional empathy was enhanced through stimulation of the MR via fludrocortisone in healthy participants and women with BPD. This review aims to integrate these findings and discuss potential mechanisms and implications.

  8. Maternal postpartum corticosterone and fluoxetine differentially affect adult male and female offspring on anxiety-like behavior, stress reactivity, and hippocampal neurogenesis.

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    Gobinath, Aarthi R; Workman, Joanna L; Chow, Carmen; Lieblich, Stephanie E; Galea, Liisa A M

    2016-02-01

    Postpartum depression (PPD) affects approximately 15% of mothers, disrupts maternal care, and can represent a form of early life adversity for the developing offspring. Intriguingly, male and female offspring are differentially vulnerable to the effects of PPD. Antidepressants, such as fluoxetine, are commonly prescribed for treating PPD. However, fluoxetine can reach offspring via breast milk, raising serious concerns regarding the long-term consequences of infant exposure to fluoxetine. The goal of this study was to examine the long-term effects of maternal postpartum corticosterone (CORT, a model of postpartum stress/depression) and concurrent maternal postpartum fluoxetine on behavioral, endocrine, and neural measures in adult male and female offspring. Female Sprague-Dawley dams were treated daily with either CORT or oil and fluoxetine or saline from postnatal days 2-23, and offspring were weaned and left undisturbed until adulthood. Here we show that maternal postpartum fluoxetine increased anxiety-like behavior and impaired hypothalamic-pituitary-adrenal (HPA) axis negative feedback in adult male, but not female, offspring. Furthermore, maternal postpartum fluoxetine increased the density of immature neurons (doublecortin-expressing) in the hippocampus of adult male offspring but decreased the density of immature neurons in adult female offspring. Maternal postpartum CORT blunted HPA axis negative feedback in males and tended to increase density of immature neurons in males but decreased it in females. These results indicate that maternal postpartum CORT and fluoxetine can have long-lasting effects on anxiety-like behavior, HPA axis negative feedback, and adult hippocampal neurogenesis and that adult male and female offspring are differentially affected by these maternal manipulations.

  9. Cannabinoids Prevent the Development of Behavioral and Endocrine Alterations in a Rat Model of Intense Stress

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    Ganon-Elazar, Eti; Akirav, Irit

    2012-01-01

    Cannabinoids have recently emerged as a possible treatment of stress- and anxiety-related disorders such as post-traumatic stress disorder (PTSD). Here, we examined whether cannabinoid receptor activation could prevent the effects of traumatic stress on the development of behavioral and neuroendocrine measures in a rat model of PTSD, the single-prolonged stress (SPS) model. Rats were injected with the CB1/CB2 receptor agonist WIN55,212-2 (WIN) systemically or into the basolateral amygdala (BLA) at different time points following SPS exposure and were tested 1 week later for inhibitory avoidance (IA) conditioning and extinction, acoustic startle response (ASR), hypothalamic-pituitary-adrenal (HPA) axis function, and anxiety levels. Exposure to SPS enhanced conditioned avoidance and impaired extinction while enhancing ASR, negative feedback on the HPA axis, and anxiety. WIN (0.5 mg/kg) administered intraperitoneally 2 or 24 h (but not 48 h) after SPS prevented the trauma-induced alterations in IA conditioning and extinction, ASR potentiation, and HPA axis inhibition. WIN microinjected into the BLA (5 μg/side) prevented SPS-induced alterations in IA and ASR. These effects were blocked by intra-BLA co-administration of the CB1 receptor antagonist AM251 (0.3 ng/side), suggesting the involvement of CB1 receptors. These findings suggest that (i) there may be an optimal time window for intervention treatment with cannabinoids after exposure to a highly stressful event, (ii) some of the preventive effects induced by WIN are mediated by an activation of CB1 receptors in the BLA, and (iii) cannabinoids could serve as a pharmacological treatment of stress- and trauma-related disorders. PMID:21918506

  10. The interaction of disrupted type II neuregulin 1 and chronic adolescent stress on adult anxiety- and fear-related behaviors.

    Science.gov (United States)

    Taylor, S B; Taylor, A R; Koenig, J I

    2013-09-26

    The incidence of anxiety, mood, substance abuse disorders and schizophrenia increases during adolescence. Epidemiological evidence confirms that exposure to stress during sensitive periods of development can create vulnerabilities that put genetically predisposed individuals at increased risk for psychiatric disorders. Neuregulin 1 (NRG1) is a frequently identified schizophrenia susceptibility gene that has also been associated with the psychotic features of bipolar disorder. Previously, we established that Type II NRG1 is expressed in the hypothalamic-pituitary-adrenal (HPA) axis neurocircuitry. We also found, using a line of Nrg1 hypomorphic rats (Nrg1(Tn)), that genetic disruption of Type II NRG1 results in altered HPA axis function and environmental reactivity. The present studies used the Nrg1(Tn) rats to test whether Type II NRG1 gene disruption and chronic stress exposure during adolescence interact to alter adult anxiety- and fear-related behaviors. Male and female Nrg1(Tn) and wild-type rats were exposed to chronic variable stress (CVS) during mid-adolescence and then tested for anxiety-like behavior, cued fear conditioning and basal corticosterone secretion in adulthood. The disruption of Type II NRG1 alone significantly impacts rat anxiety-related behavior by reversing normal sex-related differences and impairs the ability to acquire cued fear conditioning. Sex-specific interactions between genotype and adolescent stress also were identified such that CVS-treated wild-type females exhibited a slight reduction in anxiety-like behavior and basal corticosterone, while CVS-treated Nrg1(Tn) females exhibited a significant increase in cued fear extinction. These studies confirm the importance of Type II NRG1 in anxiety and fear behaviors and point to adolescence as a time when stressful experiences can shape adult behavior and HPA axis function.

  11. Bases biológicas do transtorno de estresse pós-traumático Biological basis of posttraumatic stress disorder

    Directory of Open Access Journals (Sweden)

    Frederico G Graeff

    2003-06-01

    Full Text Available A pesquisa neuroendocrinológica dos sistemas fisiológicos envolvidos no estresse evidencia hiper função do eixo simpato-adrenal em conjunto com uma redução da atividade do eixo hipotálamo-hipófise-adrenal (HHA em pacientes com estresse pós-traumático (TEPT. Uma resposta prejudicada do cortisol aos estressores parece estar associada com um aumento da vulnerabilidade ao desenvolvimento do TEPT. O excesso de catecolaminas, sem o pareamento do aumento dos corticóides promoveria uma consolidação excessiva das memórias traumáticas e a indevida generalização para outras situações estressantes. Sintomas como o entorpecimento e flashbacks têm sido relacionados com o aumento de opióides endógenos. Estudos de neuroimagem evidenciam uma redução do volume hipocampal no TEPT, que tem sido relacionada a alterações cognitivas e anormalidades do eixo HHA encontrados no TEPT.Neuroendocrinological research on the physiological systems involved in stress evidenced hyper functioning of the sympatho-adrenal axis together with reduced activity of the hypothalamic-pituitary-adrenal axis in patients with posttraumatic stress disorder (PTSD. An impaired corticoid response to stressors seems to be associated with enhanced vulnerability to PTSD. Excess catecholamines, unchecked by corticoids would promote over consolidation of traumatic memories and undue generalization to other stressful situations. Symptoms such as numbing and flashbacks have been related to endogenous opioids. Neuroimaging studies evidenced a reduction of hippocampal volume in PTSD patients, which has been related to both cognitive changes and abnormalities of the HPA axis that are found in PTSD.

  12. Chronic Unpredictable Mild Stress Induces Loss of GABA Inhibition in Corticotrophin-Releasing Hormone-Expressing Neurons through NKCC1 Upregulation.

    Science.gov (United States)

    Gao, Yonggang; Zhou, Jing-Jing; Zhu, Yun; Kosten, Therese; Li, De-Pei

    2017-01-01

    Prolonged and repeated stresses cause hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. The corticotrophin-releasing hormone (CRH)-expressing neurons in the hypothalamic paraventricular nucleus (PVN) are an essential component of the HPA axis. Chronic unpredictable mild stress (CUMS) was induced in Sprague-Dawley rats. GABA reversal potentials (EGABA) were determined by using gramicidin-perforated recordings in identified PVN-CRH neurons through expressing enhanced green fluorescent protein driven by the CRH promoter. Plasma corticosterone (CORT) levels were measured in rats implanted with a cannula targeting the lateral ventricles and PVN. Blocking the GABAA receptor in the PVN with gabazine significantly increased plasma CORT levels in unstressed rats but did not change CORT levels in CUMS rats. CUMS caused a depolarizing shift in EGABA in PVN-CRH neurons compared with EGABA in PVN-CRH neurons in unstressed rats. Furthermore, CUMS induced a long-lasting increase in expression levels of the cation chloride cotransporter Na+-K+-Cl--Cl- (NKCC1) in the PVN but a transient decrease in expression levels of K+-Cl--Cl- in the PVN, which returned to the basal level 5 days after CUMS treatment. The NKCC1 inhibitor bumetanide decreased the basal firing activity of PVN-CRH neurons and normalized EGABA and the gabazine-induced excitatory effect on PVN-CRH neurons in CUMS rats. In addition, central administration of bumetanide decreased basal circulating CORT levels in CUMS rats. These data suggest that chronic stress impairs GABAergic inhibition, resulting in HPA axis hyperactivity through upregulation of NKCC1. © 2016 S. Karger AG, Basel.

  13. Effects of childhood trauma exposure and cortisol levels on cognitive functioning among breast cancer survivors.

    Science.gov (United States)

    Kamen, Charles; Scheiber, Caroline; Janelsins, Michelle; Jo, Booil; Shen, Hanyang; Palesh, Oxana

    2017-08-14

    Cognitive functioning difficultiesin breast cancer patients receiving chemotherapy are common, but not all women experience these impairments. Exposure to childhood trauma may impair cognitive functioning following chemotherapy, and these impairments may be mediated by dysregulation of hypothalamic-pituitary-adrenal (HPA) axis function and cortisol slope. This study evaluated the association between childhood trauma exposure, cortisol, and cognition in a sample of breast cancer survivors. 56 women completed measures of trauma exposure (the Traumatic Events Survey), salivary cortisol, and self-reported cognitive functioning (the Functional Assessment of Cancer Therapy - Cognitive). We examined correlations between childhood trauma exposure and cognitive functioning, then used linear regression to control for factors associated with cognition (age, education, time since chemotherapy, depression, anxiety, and insomnia), and the MacArthur approach to test whether cortisol levels mediated the relationship between trauma and cognitive functioning. 57.1% of the sample had experienced at least one traumatic event in childhood, with 19.6% of the sample witnessing a serious injury, 17.9% experiencing physical abuse, and 14.3% experiencing sexual abuse. Childhood trauma exposure and cognitive functioning were moderately associated (r=-0.29). This association remained even when controlling for other factors associated with cognition; the final model explained 47% of the variance in cognitive functioning. The association between childhood trauma and cognitive functioning was mediated by steeper cortisol slope (partial r=0.35, p=0.02). Childhood trauma exposure is associated with self-reported cognitive functioning among breast cancer survivors and is mediated by cortisol dysregulation. Trauma should be considered, among other factors, in programs aiming to address cognition in this population. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Diurnal cortisol rhythms among Latino immigrants in Oregon, USA

    Directory of Open Access Journals (Sweden)

    Squires Erica C

    2012-06-01

    Full Text Available Abstract One of the most commonly used stress biomarkers is cortisol, a glucocorticoid hormone released by the adrenal glands that is central to the physiological stress response. Free cortisol can be measured in saliva and has been the biomarker of choice in stress studies measuring the function of the hypothalamic-pituitary-adrenal axis. Chronic psychosocial stress can lead to dysregulation of hypothalamic-pituitary-adrenal axis function and results in an abnormal diurnal cortisol profile. Little is known about objectively measured stress and health in Latino populations in the United States, yet this is likely an important factor in understanding health disparities that exist between Latinos and whites. The present study was designed to measure cortisol profiles among Latino immigrant farmworkers in Oregon (USA, and to compare quantitative and qualitative measures of stress in this population. Our results indicate that there were no sex differences in average cortisol AUCg (area under the curve with respect to the ground over two days (AvgAUCg; males = 1.38, females = 1.60; P = 0.415. AUCg1 (Day 1 AUCg and AvgAUCg were significantly negatively associated with age in men (PPPP

  15. Moxibustion upregulates hippocampal progranulin expression

    Directory of Open Access Journals (Sweden)

    Tao Yi

    2016-01-01

    Full Text Available In China, moxibustion is reported to be useful and has few side effects for chronic fatigue syndrome, but its mechanisms are largely unknown. More recently, the focus has been on the wealth of information supporting stress as a factor in chronic fatigue syndrome, and largely concerns dysregulation in the stress-related hypothalamic-pituitary-adrenal axis. In the present study, we aimed to determine the effect of moxibustion on behavioral symptoms in chronic fatigue syndrome rats and examine possible mechanisms. Rats were subjected to a combination of chronic restraint stress and forced swimming to induce chronic fatigue syndrome. The acupoints Guanyuan (CV4 and Zusanli (ST36, bilateral were simultaneously administered moxibustion. Untreated chronic fatigue syndrome rats and normal rats were used as controls. Results from the forced swimming test, open field test, tail suspension test, real-time PCR, enzyme-linked immunosorbent assay, and western blot assay showed that moxibustion treatment decreased mRNA expression of corticotropin-releasing hormone in the hypothalamus, and adrenocorticotropic hormone and corticosterone levels in plasma, and markedly increased progranulin mRNA and protein expression in the hippocampus. These findings suggest that moxibustion may relieve the behavioral symptoms of chronic fatigue syndrome, at least in part, by modulating the hypothalamic-pituitary-adrenal axis and upregulating hippocampal progranulin.

  16. The symphonic structure of childhood stress reactivity: patterns of sympathetic, parasympathetic, and adrenocortical responses to psychological challenge.

    Science.gov (United States)

    Quas, Jodi A; Yim, Ilona S; Oberlander, Tim F; Nordstokke, David; Essex, Marilyn J; Armstrong, Jeffrey M; Bush, Nicole; Obradović, Jelena; Boyce, W Thomas

    2014-11-01

    Despite widespread recognition that the physiological systems underlying stress reactivity are well coordinated at a neurobiological level, surprisingly little empirical attention has been given to delineating precisely how the systems actually interact with one another when confronted with stress. We examined cross-system response proclivities in anticipation of and following standardized laboratory challenges in 664 4- to 14-year-olds from four independent studies. In each study, measures of stress reactivity within both the locus coeruleus-norepinephrine system (i.e., the sympathetic and parasympathetic branches of the autonomic nervous system) and the corticotrophin releasing hormone system (i.e., the hypothalamic-pituitary-adrenal axis) were collected. Latent profile analyses revealed six distinctive patterns that recurred across the samples: moderate reactivity (average cross-system activation; 52%-80% of children across samples), parasympathetic-specific reactivity (2%-36%), anticipatory arousal (4%-9%), multisystem reactivity (7%-14%), hypothalamic-pituitary-adrenal axis specific reactivity (6%-7%), and underarousal (0%-2%). Groups meaningfully differed in socioeconomic status, family adversity, and age. Results highlight the sample-level reliability of children's neuroendocrine responses to stress and suggest important cross-system regularities that are linked to development and prior experiences and may have implications for subsequent physical and mental morbidity.

  17. The psychobiology of comfort eating: implications for neuropharmacological interventions.

    Science.gov (United States)

    Gibson, E Leigh

    2012-09-01

    Comfort eating, that is eating induced by negative affect, has been a core theme of explanations for overeating and obesity. Psychobiological explanations and processes underlying comfort eating are examined, as well as its prevalence in clinical and nonclinical populations, to consider who may be susceptible, whether certain foods are comforting, and what the implications for treatment may be. Comfort eating may occur in a substantial minority, particularly in women and the obese. Human and animal theories and models of emotional or stress-induced eating show some convergence, and may incorporate genetic predispositions such as impulsivity and reward sensitivity, associated with dopamine dysregulation underlying incentive salience. Comfort eaters show vulnerability to depression, emotional dysregulation and a need to escape negative affect and rumination. During negative affect, they preferentially consume sweet, fatty, energy-dense food, which may confer protection against stress, evidenced by suppression of the hypothalamic-pituitary-adrenal axis response, although activation of the hypothalamic-pituitary-adrenal axis may itself drive appetite for these palatable foods, and the risk of weight gain is increased. Benefits to mood may be transient, but perhaps sufficient to encourage repeated attempts to prolong mood improvement or distract from negative rumination. Cognitive behavioural treatments may be useful, but reliable drug therapy awaits further pharmacogenomic developments.

  18. Moxibustion upregulates hippocampal progranulin expression

    Institute of Scientific and Technical Information of China (English)

    Tao Yi; Li Qi; Ji Li; Jing-jing Le; Lei Shao; Xin Du; Jing-cheng Dong

    2016-01-01

    In China, moxibustion is reported to be useful and has few side effects for chronic fatigue syndrome, but its mechanisms are largely un-known. More recently, the focus has been on the wealth of information supporting stress as a factor in chronic fatigue syndrome, and largely concerns dysregulation in the stress-related hypothalamic-pituitary-adrenal axis. In the present study, we aimed to determine the effect of moxibustion on behavioral symptoms in chronic fatigue syndrome rats and examine possible mechanisms. Rats were subjected to a combination of chronic restraint stress and forced swimming to induce chronic fatigue syndrome. The acupointsGuanyuan (CV4) and Zusanli (ST36, bilateral) were simultaneously administered moxibustion. Untreated chronic fatigue syndrome rats and normal rats were used as controls. Results from the forced swimming test, open ifeld test, tail suspension test, real-time PCR, enzyme-linked immunosor-bent assay, and western blot assay showed that moxibustion treatment decreased mRNA expression of corticotropin-releasing hormone in the hypothalamus, and adrenocorticotropic hormone and corticosterone levels in plasma, and markedly increased progranulin mRNA and protein expression in the hippocampus. These ifndings suggest that moxibustion may relieve the behavioral symptoms of chronic fatigue syndrome, at least in part, by modulating the hypothalamic-pituitary-adrenal axis and upregulating hippocampal progranulin.

  19. Differential expression of hypothalamic fear- and stress-related genes in broiler chickens showing short or long tonic immobility.

    Science.gov (United States)

    Wang, S; Ni, Y; Guo, F; Sun, Z; Ahmed, A; Zhao, R

    2014-04-01

    The serotonin system and the hypothalamic-pituitary-adrenal axis play important roles in modulating fear and stress-coping characteristics. Tonic immobility (TI) is a fear-related phenotype, and previously we have shown that broiler chickens showing short TI (STI) duration experience better growth performance and higher adaptability to stress. Here, we sought to further elucidate the central mechanisms underlying the phenotypic differences between chickens showing STI and long TI duration, by comparing the hypothalamic expression of genes in the serotonergic system and the hypothalamic-pituitary-adrenal axis under basal and corticosterone-exposed situations. The STI broilers had significantly lower (P chickens at the level of both mRNA (P chickens, but the protein content was approximately 2 times higher (P chickens. The uncoupled expression of GR mRNA and protein was associated with significantly lower (P chickens. Corticosterone administration reduced the mRNA expression of postsynaptic serotonin receptors, 5-hydroxytryptamine receptor 1B (P = 0.059) and 5-hydroxytryptamine receptor 7 (P stress-related genes.

  20. Effect of Acute Noise Exposure on Salivary Cortisol: A Randomized Controlled Trial.

    Science.gov (United States)

    Pouryaghoub, Gholamreza; Mehrdad, Ramin; Valipouri, Alireza

    2016-10-01

    Cardiovascular adverse effects are interesting aspects of occupational noise exposure. One possible mechanism of these effects is an alternation in hypothalamic-pituitary-adrenal axis. Our aim was to measure salivary cortisol response to relatively high-intensity noise exposure in a controlled randomized trial study. We exposed 50 male volunteers to 90 dBA noise for 20 minutes and compared their level of salivary cortisol with 50 non-exposed controls. Salivary samples obtained before and after exposure. Before intervention means (SD) salivary cortisol level were 3.24 (0.47)ng/ml and 3.25 (0.41)ng/ml for exposed and non-exposed groups respectively. Mean salivary cortisol level increased to 4.17 ng/mlafter intervention in exposure group. This increment was statistically significant (P=0.00). Mean salivary cortisol level of the non-exposed group had statistically non-significant decrement after this period (0.2 ng/ml). The difference between salivary cortisol level of non-exposed and exposed groups after the intervention was statistically significant. Noise exposure may affect the hypothalamic-pituitary-adrenal axis activity, and this may be one of the mechanisms of noise exposure cardiovascular effects.

  1. Chronic early life stress induced by limited bedding and nesting (LBN) material in rodents: critical considerations of methodology, outcomes and translational potential.

    Science.gov (United States)

    Walker, Claire-Dominique; Bath, Kevin G; Joels, Marian; Korosi, Aniko; Larauche, Muriel; Lucassen, Paul J; Morris, Margaret J; Raineki, Charlis; Roth, Tania L; Sullivan, Regina M; Taché, Yvette; Baram, Tallie Z

    2017-07-12

    The immediate and long-term effects of exposure to early life stress (ELS) have been documented in humans and animal models. Even relatively brief periods of stress during the first 10 days of life in rodents can impact later behavioral regulation and the vulnerability to develop adult pathologies, in particular an impairment of cognitive functions and neurogenesis, but also modified social, emotional, and conditioned fear responses. The development of preclinical models of ELS exposure allows the examination of mechanisms and testing of therapeutic approaches that are not possible in humans. Here, we describe limited bedding and nesting (LBN) procedures, with models that produce altered maternal behavior ranging from fragmentation of care to maltreatment of infants. The purpose of this paper is to discuss important issues related to the implementation of this chronic ELS procedure and to describe some of the most prominent endpoints and consequences, focusing on areas of convergence between laboratories. Effects on the hypothalamic-pituitary adrenal (HPA) axis, gut axis and metabolism are presented in addition to changes in cognitive and emotional functions. Interestingly, recent data have suggested a strong sex difference in some of the reported consequences of the LBN paradigm, with females being more resilient in general than males. As both the chronic and intermittent variants of the LBN procedure have profound consequences on the offspring with minimal external intervention from the investigator, this model is advantageous ecologically and has a large translational potential. In addition to the direct effect of ELS on neurodevelopmental outcomes, exposure to adverse early environments can also have intergenerational impacts on mental health and function in subsequent generation offspring. Thus, advancing our understanding of the effect of ELS on brain and behavioral development is of critical concern for the health and wellbeing of both the current

  2. Neurobiological Interactions Between Stress and the Endocannabinoid System.

    Science.gov (United States)

    Morena, Maria; Patel, Sachin; Bains, Jaideep S; Hill, Matthew N

    2016-01-01

    Stress affects a constellation of physiological systems in the body and evokes a rapid shift in many neurobehavioral processes. A growing body of work indicates that the endocannabinoid (eCB) system is an integral regulator of the stress response. In the current review, we discuss the evidence to date that demonstrates stress-induced regulation of eCB signaling and the consequential role changes in eCB signaling have with respect to many of the effects of stress. Across a wide array of stress paradigms, studies have generally shown that stress evokes bidirectional changes in the two eCB molecules, anandamide (AEA) and 2-arachidonoyl glycerol (2-AG), with stress exposure reducing AEA levels and increasing 2-AG levels. Additionally, in almost every brain region examined, exposure to chronic stress reliably causes a downregulation or loss of cannabinoid type 1 (CB1) receptors. With respect to the functional role of changes in eCB signaling during stress, studies have demonstrated that the decline in AEA appears to contribute to the manifestation of the stress response, including activation of the hypothalamic-pituitary-adrenal (HPA) axis and increases in anxiety behavior, while the increased 2-AG signaling contributes to termination and adaptation of the HPA axis, as well as potentially contributing to changes in pain perception, memory and synaptic plasticity. More so, translational studies have shown that eCB signaling in humans regulates many of the same domains and appears to be a critical component of stress regulation, and impairments in this system may be involved in the vulnerability to stress-related psychiatric conditions, such as depression and posttraumatic stress disorder. Collectively, these data create a compelling argument that eCB signaling is an important regulatory system in the brain that largely functions to buffer against many of the effects of stress and that dynamic changes in this system contribute to different aspects of the stress response.

  3. The neuroenergetics of stress hormones in the hippocampus and implications for memory.

    Science.gov (United States)

    Osborne, Danielle M; Pearson-Leary, Jiah; McNay, Ewan C

    2015-01-01

    Acute stress causes rapid release of norepinephrine (NE) and glucocorticoids (GCs), both of which bind to hippocampal receptors. This release continues, at varying concentrations, for several hours following the stressful event, and has powerful effects on hippocampally-dependent memory that generally promote acquisition and consolidation while impairing retrieval. Several studies have characterized the brain's energy usage both at baseline and during memory processing, but there are few data on energy requirements of memory processes under stressful conditions. Because memory is enhanced by emotional arousal such as during stress, it is likely that molecular memory processes under these conditions differ from those under non-stressful conditions that do not activate the hypothalamic-pituitary-adrenal (HPA) axis. Mobilization of peripheral and central energy stores during stress may increase hippocampal glucose metabolism that enhances salience and detail to facilitate memory enhancement. Several pathways activated by the HPA axis affect neural energy supply and metabolism, and may also prevent detrimental damage associated with chronic stress. We hypothesize that alterations in hippocampal metabolism during stress are key to understanding the effects of stress hormones on hippocampally-dependent memory formation. Second, we suggest that the effects of stress on hippocampal metabolism are bi-directional: within minutes, NE promotes glucose metabolism, while hours into the stress response GCs act to suppress metabolism. These bi-directional effects of NE and GCs on glucose metabolism may occur at least in part through direct modulation of glucose transporter-4. In contrast, chronic stress and prolonged elevation of hippocampal GCs cause chronically suppressed glucose metabolism, excitotoxicity and subsequent memory deficits.

  4. The Neuroenergetics of Stress Hormones in the Hippocampus and Implications for Memory

    Directory of Open Access Journals (Sweden)

    Danielle eOsborne

    2015-05-01

    Full Text Available Acute stress causes rapid release of norepinephrine (NE and glucocorticoids (GCs, both of which bind to hippocampal receptors. This release continues, at varying concentrations, for several hours following the stressful event, and has powerful effects on hippocampally-dependent memory that generally promote acquisition and consolidation while impairing retrieval. Several studies have characterized the brain's energy usage both at baseline and during memory processing, but there are few data on energy requirements of memory processes under stressful conditions. Because memory is enhanced by emotional arousal such as during stress, it is likely that molecular memory processes under these conditions differ from those under non-stressful conditions that do not activate the hypothalamic-pituitary-adrenal (HPA axis. Mobilization of peripheral and central energy stores during stress may increase hippocampal glucose metabolism that enhances salience and detail to facilitate memory enhancement. Several pathways activated by the HPA axis affect neural energy supply and metabolism, and may also prevent detrimental damage associated with chronic stress. We hypothesize that alterations in hippocampal metabolism during stress are key to understanding the effects of stress hormones on hippocampally-dependent memory formation. Second, we suggest that the effects of stress on hippocampal metabolism are bi-directional: within minutes, NE promotes glucose metabolism, while hours into the stress response GCs act to suppress metabolism. These bi-directional effects of NE and GCs on glucose metabolism may occur at least in part through direct modulation of glucose transporter-4. In contrast, chronic stress and prolonged elevation of hippocampal GCs cause chronically suppressed glucose metabolism, excitotoxicity and subsequent memory deficits.

  5. High cortisol levels are associated with low quality food choice in type 2 diabetes.

    Science.gov (United States)

    Duong, Michelle; Cohen, Jessica I; Convit, Antonio

    2012-02-01

    Hypothalamic-pituitary-adrenal (HPA) axis control may be impaired in type 2 diabetes (T2DM). Glucocorticoids increase consumption of low quality foods high in calories, sugar, and fat. We explored the relationship between cortisol levels, poor blood glucose control, and food quality choice in T2DM. Twenty-seven healthy controls were age-, gender- and education-matched to 27 T2DM participants. Standard clinical blood tests and cortisol values were measured from fasting blood samples. Participants recorded all consumed food and drink items in a consecutive 3-day food diary. Diaries were analyzed for "high quality" and "low quality" foods using a standardized method with high reliability (0.97 and 0.86, respectively). Controlling for education, body mass index (BMI) and hemoglobin A1C (HbA1C), log-transformed cortisol (LogC) predicted the percent of low quality foods (R (2) = 0.092, β = 0.360, P foods chosen. Controlling for education, BMI, and LogC, HbA1C significantly predicted both the percent of low quality foods (ΔR (2) = 0.079, β = 0.348, P = 0.024) and high quality foods chosen (ΔR (2) = 0.085, β = -0.362, P = 0.022). The relationship between HbA1C and low quality food choice may be mediated by cortisol, controlling for BMI and education (P food choice (P food choice may be partially mediated by cortisol. Poor blood glucose control may cause HPA axis disruption, increased consumption of low quality foods.

  6. The neuroenergetics of stress hormones in the hippocampus and implications for memory

    Science.gov (United States)

    Osborne, Danielle M.; Pearson-Leary, Jiah; McNay, Ewan C.

    2015-01-01

    Acute stress causes rapid release of norepinephrine (NE) and glucocorticoids (GCs), both of which bind to hippocampal receptors. This release continues, at varying concentrations, for several hours following the stressful event, and has powerful effects on hippocampally-dependent memory that generally promote acquisition and consolidation while impairing retrieval. Several studies have characterized the brain's energy usage both at baseline and during memory processing, but there are few data on energy requirements of memory processes under stressful conditions. Because memory is enhanced by emotional arousal such as during stress, it is likely that molecular memory processes under these conditions differ from those under non-stressful conditions that do not activate the hypothalamic-pituitary-adrenal (HPA) axis. Mobilization of peripheral and central energy stores during stress may increase hippocampal glucose metabolism that enhances salience and detail to facilitate memory enhancement. Several pathways activated by the HPA axis affect neural energy supply and metabolism, and may also prevent detrimental damage associated with chronic stress. We hypothesize that alterations in hippocampal metabolism during stress are key to understanding the effects of stress hormones on hippocampally-dependent memory formation. Second, we suggest that the effects of stress on hippocampal metabolism are bi-directional: within minutes, NE promotes glucose metabolism, while hours into the stress response GCs act to suppress metabolism. These bi-directional effects of NE and GCs on glucose metabolism may occur at least in part through direct modulation of glucose transporter-4. In contrast, chronic stress and prolonged elevation of hippocampal GCs cause chronically suppressed glucose metabolism, excitotoxicity and subsequent memory deficits. PMID:25999811

  7. The Role of the Endocannabinoid System in the Brain-Gut Axis.

    Science.gov (United States)

    Sharkey, Keith A; Wiley, John W

    2016-08-01

    The actions of cannabis are mediated by receptors that are part of an endogenous cannabinoid system. The endocannabinoid system (ECS) consists of the naturally occurring ligands N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol (2-AG), their biosynthetic and degradative enzymes, and the cannabinoid (CB) receptors CB1 and CB2. The ECS is a widely distributed transmitter system that controls gut functions peripherally and centrally. It is an important physiologic regulator of gastrointestinal motility. Polymorphisms in the gene encoding CB1 (CNR1) have been associated with some forms of irritable bowel syndrome. The ECS is involved in the control of nausea and vomiting and visceral sensation. The homeostatic role of the ECS also extends to the control of intestinal inflammation. We review the mechanisms by which the ECS links stress and visceral pain. CB1 in sensory ganglia controls visceral sensation, and transcription of CNR1 is modified through epigenetic processes under conditions of chronic stress. These processes might link stress with abdominal pain. The ECS is also involved centrally in the manifestation of stress, and endocannabinoid signaling reduces the activity of hypothalamic-pituitary-adrenal pathways via actions in specific brain regions, notably the prefrontal cortex, amygdala, and hypothalamus. Agents that modulate the ECS are in early stages of development for treatment of gastrointestinal diseases. Increasing our understanding of the ECS will greatly advance our knowledge of interactions between the brain and gut and could lead to new treatments for gastrointestinal disorders.

  8. Safety and tolerability of treatments for allergic rhinitis in children.

    Science.gov (United States)

    Baena-Cagnani, Carlos E

    2004-01-01

    Allergic rhinitis is a common condition in adults and children and can have a large impact on patients' health and quality of life. The aim of current allergic rhinitis therapies is to treat the subjective symptoms and to improve objective measures of the disease. Of the available treatment options for paediatric allergic rhinitis, the newer oral antihistamines and intranasal corticosteroids are first-line treatments.First-generation antihistamines are associated with unwanted adverse effects such as cardiotoxicity, sedation and impairment of psychomotor function. Despite results from studies using first-generation antihistamines demonstrating impairment of cognitive and academic function in children, many of these agents are still commonly given to patients. The newer antihistamines, developed with the aim of being more specific for the histamine H(1) receptor and of overcoming these adverse effects, are the medication of choice in patients with mild intermittent allergic rhinitis. For children lipophilicity, volume of distribution, and half-life. A number of studies - utilising hypothalamic-pituitary-adrenal axis function tests such as plasma cortisol levels, 24-hour urinary-free cortisol tests; stimulation tests with corticotropin (adrenocorticotropic hormone), lypressin, and corticotropin-releasing hormone; and growth assessment studies using knemometry and stadiometry - have indicated that these intranasal corticosteroids are well-tolerated in paediatric patients and do not significantly affect growth. The wealth of clinical data and the recommendations from evidence-based guidelines suggest that both antihistamines and intranasal corticosteroids have good safety profiles in children. Nevertheless, growth should be regularly monitored in children receiving intranasal corticosteroids. Other treatments such as immunotherapy, local chromones and decongestants can also be beneficial in managing paediatric allergic rhinitis, and therapies should be considered on an

  9. Effects of interpersonal violence-related post-traumatic stress disorder (PTSD) on mother and child diurnal cortisol rhythm and cortisol reactivity to a laboratory stressor involving separation.

    Science.gov (United States)

    Cordero, Maria I; Moser, Dominik A; Manini, Aurelia; Suardi, Francesca; Sancho-Rossignol, Ana; Torrisi, Raffaella; Rossier, Michel F; Ansermet, François; Dayer, Alexandre G; Rusconi-Serpa, Sandra; Schechter, Daniel S

    2017-04-01

    Women who have experienced interpersonal violence (IPV) are at a higher risk to develop posttraumatic stress disorder (PTSD), with dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and impaired social behavior. Previously, we had reported impaired maternal sensitivity and increased difficulty in identifying emotions (i.e. alexithymia) among IPV-PTSD mothers. One of the aims of the present study was to examine maternal IPV-PTSD salivary cortisol levels diurnally and reactive to their child's distress in relation to maternal alexithymia. Given that mother-child interaction during infancy and early childhood has important long-term consequences on the stress response system, toddlers' cortisol levels were assessed during the day and in response to a laboratory stressor. Mothers collected their own and their 12-48month-old toddlers' salivary samples at home three times: 30min after waking up, between 2-3pm and at bedtime. Moreover, mother-child dyads participated in a 120-min laboratory session, consisting of 3 phases: baseline, stress situation (involving mother-child separation and exposure to novelty) and a 60-min regulation phase. Compared to non-PTSD controls, IPV-PTSD mothers - but not their toddlers, had lower morning cortisol and higher bedtime cortisol levels. As expected, IPV-PTSD mothers and their children showed blunted cortisol reactivity to the laboratory stressor. Maternal cortisol levels were negatively correlated to difficulty in identifying emotions. Our data highlights PTSD-IPV-related alterations in the HPA system and its relevance to maternal behavior. Toddlers of IPV-PTSD mothers also showed an altered pattern of cortisol reactivity to stress that potentially may predispose them to later psychological disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Activation of cannabinoid CB1 receptors in the ventral hippocampus improved stress-induced amnesia in rat.

    Science.gov (United States)

    Mohammadmirzaei, Negin; Rezayof, Ameneh; Ghasemzadeh, Zahra

    2016-09-01

    The ventral hippocampus (VH) has a high distribution of cannabinoid CB1 receptors which are important in modulating stress responses. Stress exposure activates the hypothalamic-pituitary-adrenal axis (HPA) which can impact hippocampal formation to change hippocampus-based memories. The purpose of the present study was to determine the possible role of the VH cannabinoid CB1 receptors in stress-induced amnesia using a step-through passive avoidance procedure in male Wistar rats. In order to induce acute stress, the animals were placed on an elevated platform for different time periods (10, 20 and 30min). Our results indicated that post-training 20 and 30min exposure to stress, but not 10min, induced amnesia. Post-training microinjection of a cannabinoid CB1 receptor agonist, arachydonilcyclopropylamide (ACPA; 2.5-7.5ng/rat) into the VH (intra-VH) induced amnesia. Interestingly, post-training intra-VH microinjection of the same doses of ACPA improved stress-induced amnesia. On the other hand, post-training intra-VH microinjection of a selective CB1 receptor antagonist, AM-251 (20-50ng/rat) with exposure to an ineffective stress (10min) potentiated the effect of stress on memory consolidation and induced amnesia. It should be noted that post-training intra-VH microinjection of the same doses of AM-251 alone had no effect on memory consolidation. Our results revealed that post-training intra-VH microinjection of AM-251, prior to ACPA microinjection, inhibited the reversal effect of ACPA on acute elevated platform stress. Taken together, it can be concluded that exposure to post-training inescapable stress impaired memory consolidation. The impairing effects of stress on memory retrieval may be mediated by the VH cannabinoid CB1 receptors.

  11. Effect of neonatal handling on adult rat spatial learning and memory following acute stress.

    Science.gov (United States)

    Stamatakis, A; Pondiki, S; Kitraki, E; Diamantopoulou, A; Panagiotaropoulos, T; Raftogianni, A; Stylianopoulou, F

    2008-03-01

    Brief neonatal handling permanently alters hypothalamic-pituitary-adrenal axis function resulting in increased ability to cope with stress. Since stress is known to affect cognitive abilities, in the present study we investigated the effect of brief (15 min) handling on learning and memory in the Morris water maze, following exposure to an acute restraint stress either before training or recall. Exposure of non-handled rats to the acute stress prior to training resulted in quicker learning of the task, than in the absence of the stressor. When acute stress preceded acquisition, male handled rats showed an overall better learning performance, and both sexes of handled animals were less impaired in the subsequent memory trial, compared to the respective non-handled. In addition, the number of neurons immunoreactive for GR was higher in all areas of Ammon's horn of the handled rats during the recall. In contrast, the number of neurons immunoreactive for MR was higher in the CA1 and CA2 areas of the non-handled males. When the acute restraint stress was applied prior to the memory test, neonatal handling was not effective in preventing mnemonic impairment, as all animal groups showed a similar deficit in recall. In this case, no difference between handled and non-handled rats was observed in the number of GR positive neurons in the CA2 and CA3 hippocampal areas during the memory test. These results indicate that early experience interacts with sex and acute stress exposure in adulthood to affect performance in the water maze. Hippocampal corticosterone receptors may play a role in determining the final outcome.

  12. Milk-based phospholipids increase morning cortisol availability and improve memory in chronically stressed men.

    Science.gov (United States)

    Schubert, Melanie; Contreras, Carina; Franz, Nadin; Hellhammer, Juliane

    2011-06-01

    Phospholipids (PLs) have been shown to dampen the activity and reactivity of the hypothalamic-pituitary-adrenal axis (HPAA). To further investigate stress protective effects of PL, 75 chronically stressed men aged 30 to 51 years were enrolled in a randomized and placebo-controlled trial. The subjects received a bovine milk drink with either 0.5% PL, 1% PL, or a placebo for 42 days to test the hypothesis that supplementation with specific phospholipids would normalize the cortisol response of the HPAA. For determining HPAA activity, the cortisol awakening response was studied before and after treatment. In addition, participants were exposed to an acute stressor, the Trier Social Stress Test, to assess treatment effects on stress reactivity and stress-related memory impairment. After receiving PL-enriched milk, both PL groups showed a delayed decline from peak levels in morning salivary cortisol, suggesting a prolonged availability of free cortisol. Treatment with 0.5% PL additionally resulted in a stronger increase of cortisol after awakening, whereas no such differences could be observed in the 1% PL group and the placebo group, respectively. The acute stress response did not significantly differ among placebo and PL groups. An exploratory data analysis further revealed that elderly participants receiving the higher PL dosage had a significant better memory performance after the Trier Social Stress Test as compared with elderly participants from the placebo and low-PL dosage group; no such difference was observed at baseline. Our results suggest that PL may increase the availability of cortisol in chronically stressed men and may attenuate stress-induced memory impairments. Results of the present study are discussed within the context of previous research and current state of knowledge. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. The immune response to surgery and trauma: Implications for treatment.

    Science.gov (United States)

    Marik, Paul E; Flemmer, Mark

    2012-10-01

    Infection after surgery and trauma is a major cause of increased morbidity, mortality, and cost. Alterations of the hosts immune system following these insults is believed to be responsible for the increased risk of infection. The hosts' immune response to tissue injury is widely believed to follow a bimodal response, with the systemic inflammatory response syndrome (SIRS) followed by the compensated anti-inflammatory response syndrome (CARS). Recent data, however, suggests that his paradigm may not be correct. We reviewed the literature to describe the immunological changes following surgery and trauma and possible therapeutic interventions to limit this process. Physical injury related to trauma and surgery increase the expression of T-helper 2 (Th2) lymphocytes which cause impaired cell mediated immunity (CMI). Activation of the hypothalamic-pituitary-adrenal (HPA) axis and sympathoadrenal system (SAS) with the release of cortisol and catecholamines appear to be responsible for altering the Th1/Th2 balance. Decreased expression and signalling of interleukin-12 (IL-12) and increased expression of T regulatory cells (Tregs) appear to play a central role in mediating this immune depression. Furthermore, Th2 cytokines increase the expression of arginase-1 (ARG1) in myeloid-derived suppressor cells (MDSC's) causing an arginine deficient state, which further impairs lymphocyte function. Immunomodulating diets (IMDs) containing supplemental arginine and omega-3 fatty acids have been demonstrated to restore the Th1/Th2 balance after surgical trauma and to reduce the risk of infectious complications. β-adrenergic receptor blockage reverses the Th-1 to Th2 shift and preliminary data suggests that such therapy may be beneficial. Tissue injury following surgery and trauma results in depressed CMI leading to an increased risk of infections. The peri-operative use of IMDs appear to reverse this immunosuppression and decrease the risk of postoperative complications. While

  14. Stress and obesity/metabolic syndrome in childhood and adolescence.

    Science.gov (United States)

    Pervanidou, Panagiota; Chrousos, George P

    2011-09-01

    Chronic distress contributes to the development of obesity and comorbid states. Stress is the disturbance of the complex dynamic equilibrium that all organisms must maintain, and is associated with activation of the Stress system comprising of the hypothalamic-pituitary-adrenal axis and the arousal/sympathetic nervous systems. The stress system functions in a baseline circadian fashion and interacts with other systems of the organism to regulate a variety of behavioral, endocrine, metabolic, immune and cardiovascular functions. The experience of perceived or real uncontrollable intense and/or chronic stress (distress) may lead to several psychopathologic conditions, including anxiety, depressive and psychosomatic disorders, substance abuse, obesity and the metabolic syndrome, and osteoporosis, as well as impaired reproductive and immune functions. Developing children and adolescents are particularly vulnerable to the effects of chronic stress. Both behavioral and biological pathways are involved in the connection between chronic stress and obesity in adults and children. Emotional "comfort" eating, lack of sleep, impulsive behaviours and selection of specific foods often characterize stressed individuals. In addition to specific behaviours, dysregulation of the stress system through increased secretion of cortisol and catecholamines, especially in the evening hours, and in concert with concurrently elevated insulin concentrations, leads to development of central obesity, insulin resistance and the metabolic syndrome. In children, chronic alterations in cortisol secretion may have additional effects on cognitive and emotional development, timing of puberty and final stature. Obese children and adolescents are frequently entangled in a vicious cycle between distress, impairing self-image and distorted self-image, maintaining and worsening distress.

  15. Impaired CBS-H2S signaling axis contributes to MPTP-induced neurodegeneration in a mouse model of Parkinson's disease.

    Science.gov (United States)

    Yuan, Yu-Qing; Wang, Ya-Li; Yuan, Bao-Shi; Yuan, Xin; Hou, Xiao-Ou; Bian, Jin-Song; Liu, Chun-Feng; Hu, Li-Fang

    2017-08-01

    that impaired CBS-H2S axis may contribute to the pathogenesis of PD, and that modulation of this axis may become a novel therapeutic approach for PD. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Psiconeuroendocrinologia do transtorno de estresse pós-traumático Psychoneuroendocrinology of posttraumatic stress disorder

    Directory of Open Access Journals (Sweden)

    Juliana Elena Ruiz

    2007-05-01

    Full Text Available OBJETIVO: Os autores realizaram uma revisão tradicional da literatura sobre os achados neurobiológicos das disfunções do eixo hipotálamo-pituitária-adrenal associados ao transtorno de estresse pós-traumático. MÉTODO: Os achados científicos relevantes foram descritos de acordo com a ordem cronológica de publicação e as características dos estudos, se eram pré-clínicos, relacio-nados à violência precoce como fator de risco e, finalmente, achados clínicos em pacientes portadores de transtorno de estresse pós-traumático. RESULTADOS: Foi encontrada uma literatura rica de achados a respeito de disfunções do eixo hipotálamo-pituitária-adrenal e transtorno de estresse pós-traumático. Os achados mostraram que o transtorno de estresse pós-traumático está associado a disfunções deste eixo e de estruturas cerebrais como o córtex pré-frontal, hipocampo e amídala. Os pacientes com transtorno de estresse pós-traumático apresentam um aumento da responsividade dos receptores de glicocorticóides, sugerindo que a inibição do feedback negativo tem um papel importante na fisiopatologia do quadro. Estudos pré-clínicos com modelos animais de deprivação maternal evidenciaram que, dependendo de quando o trauma ocorre, a disfunção do eixo será diferente. Os estudos clínicos mostram que o estresse precoce está relacionado ao desenvolvimento de psicopatologia durante a vida adulta. CONCLUSÕES: As disfunções do eixo hipotálamo-pituitária-adrenal relacionadas ao transtorno de estresse pós-traumático são evidências robustas e os mecanismos subjacentes a ele são cada vez mais compreendidos.OBJECTIVE: To review the literature on neurobiological findings related to hypothalamic-pituitary-adrenal axis dysfunctions associated with posttraumatic stress disorder. METHOD: The relevant scientific findings were described according to the date of publication and the characteristics of the studies: preclinical studies, studies on

  17. A systematic review of randomised control trials on the effects of yoga on stress measures and mood.

    Science.gov (United States)

    Pascoe, Michaela C; Bauer, Isabelle E

    2015-09-01

    Stress related disorders such as depression and anxiety are leading sources of disability worldwide, and current treatment methods such as conventional antidepressant medications are not beneficial for all individuals. There is evidence that yoga has mood-enhancing properties possibly related to its inhibitory effects on physiological stress and inflammation, which are frequently associated with affective disorders. However the biological mechanisms via which yoga exerts its therapeutic mood-modulating effects are largely unknown. This systematic review investigates the effects of yoga on sympathetic nervous system and hypothalamic pituitary adrenal axis regulation measures. It focuses on studies collecting physiological parameters such as blood pressure, heart rate, cortisol, peripheral cytokine expression and/or structural and functional brain measures in regions involved in stress and mood regulation. Overall the 25 randomised control studies discussed provide preliminary evidence to suggest that yoga practice leads to better regulation of the sympathetic nervous system and hypothalamic-pituitary-adrenal system, as well as a decrease in depressive and anxious symptoms in a range of populations. Further research is warranted to confirm these preliminary findings and facilitate implementation in clinical settings.

  18. Probiotics treatment improves diabetes-induced impairment of synaptic activity and cognitive function: behavioral and electrophysiological proofs for microbiome-gut-brain axis.

    Science.gov (United States)

    Davari, S; Talaei, S A; Alaei, H; Salami, M

    2013-06-14

    Diabetes mellitus-induced metabolic disturbances underlie the action of many systems including some higher functions of the brain such as learning and memory. Plenty of evidence supports the effects of probiotics on the function of many systems including the nervous system. Here we report the effect of probiotics treatment on the behavioral and electrophysiological aspects of learning and memory disorders. Diabetic rats were made through intraperitoneal injection of streptozocin. The control and diabetic rats were fed with either normal regimen (control rats recieving normal regimen (CO) and diabetics rats receiving normal regimen (DC), respectively) or normal regimen plus probiotic supplementation for 2months (control rats receiving probiotic supplementation (CP) and diabetics rats recieving probiotic supplementation (DP), respectively). The animals were first introduced to spatial learning task in the Morris water maze. Then, in electrophysiological experiments, stimulating the Schaffer collaterals the basic and potentiated excitatory postsynaptic potential (EPSPs) were recorded in the CA1 area of the hippocampus. Finally, the serum levels of glucose, insulin, superoxide dismutase and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured. We found that probiotics administration considerably improved the impaired spatial memory in the diabetic animals. The probiotics supplementation in the diabetic rats recovered the declined basic synaptic transmission and further restored the hippocampal long-term potentiation (LTP). While the probiotics administration enhanced the activation of superoxide dismutase and increased the insulin level of serum it decreased both the glucose level of serum and the 8-OHdG factor. From the present results we concluded that probiotics efficiently reverse deteriorated brain functions in the levels of cognitive performances and their proposed synaptic mechanisms in diabetes mellitus. These considerations imply on the necessity of an optimal

  19. Fear extinction and BDNF: translating animal models of PTSD to the clinic.

    Science.gov (United States)

    Andero, R; Ressler, K J

    2012-07-01

    Brain-derived neurotrophic factor (BDNF) is the most studied neurotrophin involved in synaptic plasticity processes that are required for long-term learning and memory. Specifically, BDNF gene expression and activation of its high-affinity tropomyosin-related kinase B (TrkB) receptor are necessary in the amygdala, hippocampus and prefrontal cortex for the formation of emotional memories, including fear memories. Among the psychiatric disorders with altered fear processing, there is post-traumatic stress disorder (PTSD) which is characterized by an inability to extinguish fear memories. Since BDNF appears to enhance extinction of fear, targeting impaired extinction in anxiety disorders such as PTSD via BDNF signalling may be an important and novel way to enhance treatment efficacy. The aim of this review is to provide a translational point of view that stems from findings in the BDNF regulation of synaptic plasticity and fear extinction. In addition, there are different systems that seem to alter fear extinction through BDNF modulation like the endocannabinoid system and the hypothalamic-pituitary adrenal axis. Recent work also finds that the pituitary adenylate cyclase-activating polypeptide and PAC1 receptor, which are upstream of BDNF activation, may be implicated in PTSD. Especially interesting are data that exogenous fear extinction enhancers such as antidepressants, histone deacetylases inhibitors and D-cycloserine, a partial N-methyl d-aspartate agonist, may act through or in concert with the BDNF-TrkB system. Finally, we review studies where recombinant BDNF and a putative TrkB agonist, 7,8-dihydroxyflavone, may enhance extinction of fear. These approaches may lead to novel agents that improve extinction in animal models and eventually humans.

  20. Sex differences in stress-related receptors: ″micro″ differences with ″macro″ implications for mood and anxiety disorders

    Directory of Open Access Journals (Sweden)

    Bangasser Debra A

    2013-01-01

    Full Text Available Abstract Stress-related psychiatric disorders, such as unipolar depression and post-traumatic stress disorder (PTSD, occur more frequently in women than in men. Emerging research suggests that sex differences in receptors for the stress hormones, corticotropin releasing factor (CRF and glucocorticoids, contribute to this disparity. For example, sex differences in CRF receptor binding in the amygdala of rats may predispose females to greater anxiety following stressful events. Additionally, sex differences in CRF receptor signaling and trafficking in the locus coeruleus arousal center combine to make females more sensitive to low levels of CRF, and less adaptable to high levels. These receptor differences in females could lead to hyperarousal, a dysregulated state associated with symptoms of depression and PTSD. Similar to the sex differences observed in CRF receptors, sex differences in glucocorticoid receptor (GR function also appear to make females more susceptible to dysregulation after a stressful event. Following hypothalamic pituitary adrenal axis activation, GRs are critical to the negative feedback process that inhibits additional glucocorticoid release. Compared to males, female rats have fewer GRs and impaired GR translocation following chronic adolescent stress, effects linked to slower glucocorticoid negative feedback. Thus, under conditions of chronic stress, attenuated negative feedback in females would result in hypercortisolemia, an endocrine state thought to cause depression. Together, these studies suggest that sex differences in stress-related receptors shift females more easily into a dysregulated state of stress reactivity, linked to the development of mood and anxiety disorders. The implications of these receptor sex differences for the development of novel pharmacotherapies are also discussed.