The Heart as a Psychoneuroendocrine and Immunoregulatory Organ.

The heart can be viewed not just as muscle pump but also as an important checkpoint for a complex network of nervous, endocrine, and immune signals. The heart is able to process neurological signals independently from the brain and to crosstalk with the endocrine and immune systems. The heart communicates with the psyche through the neuro-endocrine-immune system in a highly integrated way, in order to maintain the homeostasis of the whole body with peculiarities specific to males and females.

Hair cortisol: A new tool for evaluating stress in programs of stress management.

AIMS: Longitudinal and experimental studies have shown that chronic stress contributes to the onset and progression of different diseases. Although it is not possible to eliminate stress completely, people can learn to manage it by participating in different kinds of stress management interventions. This study examined the effectiveness of stress management interventions on neuroendocrine responses in stressed students and health professionals, by measuring hair cortisol in comparison to salivary cortisol. MAIN METHODS: Salivary and hair cortisol measurements were performed in 37 subjects (31women, 6 men; mean age 34.0±10.6) who attended to a Coping Stress and Quality of Care Program at the University of Buenos Aires. Cortisol was measured at the beginning and at the end of the program. The State-Trait Anxiety Inventory STAI was used to evaluate state and trait anxiety. KEY FINDINGS: In subjects who completed the program, no differences were observed in salivary cortisol levels between the first and the last session. However, in these subjects, hair cortisol obtained in the last session was significantly lower than hair cortisol in the first session. SIGNIFICANCE: Hair cortisol appears to be a better biomarker than salivary cortisol for evaluation of the effectiveness of a stress reduction program and it seems to be a better indicator of stress system dysregulation as well.

Which patient requires neuroendocrine assessment following traumatic brain injury, when and how?

Traumatic brain injury (TBI) is an important public health problem, particularly among young adults in industrialized countries. Hypopituitarism is a common occurrence among survivors of TBI and may contribute to the associated morbidity seen in the acute and chronic phases following injury. The available data suggest that survivors of moderate to severe TBI should undergo screening for hypopituitarism particularly in the first year after injury. This requires a close liaison between endocrinologists, neurosurgeons, neuropsychologists, intensive care and rehabilitation physicians. Patients who suffer milder forms of TBI should also be considered for endocrine evaluation if they exhibit any clinical features of pituitary hormone deficiencies.

AMPK and the neuroendocrine regulation of appetite and energy expenditure.

This review highlights recent advances in the hormonal control of hypothalamic AMPK activity and the impact on appetite and energy metabolism. AMPK is an intracellular energy sensor that switches off ATP-consuming pathways and switches on ATP-producing pathways such as glucose uptake and fatty acid oxidation. In this regard, it is well positioned to respond to dynamic changes in metabolic state and nutritional over- or under-supply. Within the hypothalamus, AMPK responds to peripheral hormones that convey metabolic information based on increased plasma concentrations. For example, negative energy balance increases plasma ghrelin concentrations, increases hypothalamic AMPK and drives food intake. Conversely, plasma leptin concentrations are secreted in proportion to adipose levels and leptin suppresses hypothalamic AMPK activity and restricts food intake. This review explains that hypothalamic AMPK mediates neuroendocrine feedback control of energy metabolism. A current working model suggests that endocrine feedback influences hypothalamic AMPK via a number of mechanisms designed to shift an organism from negative to neutral energy balance. These mechanisms include (1) ghrelin stimulation of AMPK in NPY/AgRP in the arcuate nucleus (2) ghrelin stimulation of AMPK in the ventromedial hypothalamic nucleus, (3) a novel ghrelin-stimulated AMPK-dependent presynaptic mechanism that sustains AgRP neuron firing via a local synaptic memory system, (4) adiponectin stimulation of hypothalamic AMPK and (5) hypothalamic AMPK control of energy expenditure by thyroid hormone or leptin. The number of diverse mechanisms ensures hypothalamic AMPK drives the shift from negative to neutral energy balance and underscores the fundamental importance of hypothalamic AMPK to maintain neutral energy balance.

Neuroendocrine assessment of serotonergic, dopaminergic, and noradrenergic functions in alcohol-dependent individuals.

BACKGROUND: Alcohol dependence has been associated with reduced function of serotonin, dopamine as well as noradrenaline activities in several neuroendocrine studies. To our knowledge, there is, however, no study investigating all these 3 systems with the use of neuroendocrine methods in one and the same alcohol-dependent individual. METHODS: Alcohol-dependent individuals (n = 42) and controls (n = 28) participated in the neuroendocrine test series. Central serotonergic neurotransmission was assessed by the prolactin (PRL) response to citalopram (CIT). The postsynaptic DRD2 function was measured by the growth hormone (GH) response to apomorphine (APO) and the postsynaptic α2-adrenoceptor function by GH response to clonidine (CLON). RESULTS: In the alcohol-dependent individuals, the PRL concentrations were significantly lower at the time points 240 minutes and 300 minutes after CIT administration and mean delta PRL value was significantly reduced by 45% in comparison with controls. There were no significant differences in APO-GH and CLON-GH concentrations at any time points or in mean delta GH values between the groups. An impaired monoaminergic profile, including all 3 systems, was significantly more frequent in alcohol-dependent individuals than controls (43% vs. 6% respectively). CONCLUSIONS: The monoaminergic dysfunction was restricted to an impairment of the serotonergic system, suggesting that this system is especially vulnerable to long-term and excessive alcohol consumption. Moreover, impaired monoaminergic profiles, including low responses in 2 or 3 systems, were more frequently observed in alcohol-dependent individuals than in controls. Such impaired profiles may be of clinical importance, but further studies are needed.

State, not trait, neuroendocrine function predicts costly reactive aggression in men after social exclusion and inclusion.

Social exclusion increases aggressive behaviour, and the possible neuroendocrine underpinnings of the effect are largely unknown. Here, we examined the extent to which testosterone and cortisol responses to social exclusion would predict subsequent reactive aggression. Men were randomly assigned to a social exclusion (SE) or inclusion (SI) condition of 'Cyberball', a computer ball-toss game. Aggression was then measured using the Point Subtraction Aggression Paradigm (PSAP). Saliva was collected at three points for the measurement of testosterone and cortisol. Regression analyses indicated that testosterone concentrations 10-min into the PSAP (controlling for pre- and post-Cyberball testosterone) were positively correlated with aggressive behaviour, irrespective of SI/SE. Post hoc analyses for the conditions separately, however, suggested the relationship was stronger for SI men (R(2)(change)=13.3%, F(1,)(29)=5.28, p=0.03) than for SE men (R(2)(change)=1.8%, F(1,)(26)=0.49, p=0.49). Aggressive behaviour was also positively correlated with cortisol concentrations 10-min into the PSAP (controlling for pre- and post-Cyberball cortisol) irrespective of SE/SI. When both hormones were included in the regression model, the interaction of baseline 'Cortisol'×'Testosterone'×'Experimental Group' approached significance (R(2)(change)=5.4%, F(1,)(55)=3.53, p=0.07), but no significant effects were observed in either group alone. The findings add to evidence that individual differences in state neuroendocrine function map onto variability in human social behaviour.

Neuroendocrine and psychological assessment in a guinness 10 days scuba dive.

This study was designed to evaluate physiological and psychological stress parameters in 2 professional trained scuba divers, using a unique physiopathologic model, offered by the guinness 240 hours scuba dive. Two scuba dive masters have spent 240 hours at 6 - 8 meters depth (26.4 ft) in Ponza Island water (Italy). Blood samples were collected daily in the underwater bell; samples were carried out of water in waterproof bags. Breath samples were collected, measuring ethylene release. Psychological assessment was performed using the State and Trait Anxiety Inventory and the Zung self-rating depression scale. In the studied subjects, cortisol and prolactin showed physiological pulsatile secretion. Breath ethylene didn't exceed normal values. At the start of the study, no subjects showed high levels of state anxiety, trait anxiety and current depression. Psychometric scales scores remained steady during the diving period and no subjects showed anxiety and/or depression and/or panic symptoms during the time of observation. The present study shows that, although the long-time diving, well trained professional divers did not develop anxiety and/or depression. No subject discontinued the diving due to occurred psychological disorders or systemic events. The present report shows that the long-term diving permanence is possible, at least in well trained scuba divers.

Immunohistochemical and quantitative mRNA assessment of ghrelin expression in gastric and oesophageal adenocarcinoma.

BACKGROUND: Ghrelin is an orexigenic gut peptide produced predominantly by the stomach. Gastric mucosal ghrelin production could be compromised by an infiltrating adenocarcinoma. AIMS: To assess the expression of ghrelin mRNA and peptide in oesophagogastric adenocarcinomas and adjacent non-neoplastic mucosa. METHODS: 10 gastric and 22 oesophageal adenocarcinoma archival samples were randomly selected from a database. The presence of ghrelin-positive cells was assessed in cancer and corresponding non-neoplastic mucosa by immunohistochemistry. Quantitative reverse transcriptase polymerase chain reaction (PCR) for ghrelin mRNA was also performed on 24 gastric and 8 oesophageal adenocarcinoma specimens and adjacent non-neoplastic mucosa. RESULTS: Immunohistochemistry and reverse transcriptase PCR confirm a negligible expression of ghrelin in adenocarcinoma specimens. By contrast, non-neoplastic gastric mucosa was rich in ghrelin-positive cells and ghrelin mRNA. The number (median and range) of ghrelin-positive cells per 2 mm section of non-neoplastic mucosa was 73 (45-215) in the corpus; this was significantly higher than in cardia mucosa (9 (0-64), p<0.001) and antral mucosa (5 (0-14), p<0.001). CONCLUSIONS: Gastric and oesophageal adenocarcinomas have no ghrelin-producing cells. The highest level of ghrelin expression was noted in the non-neoplastic mucosa of the gastric corpus. Disruption of the gastric ghrelin-producing mechanism may occur during oesophagogastric malignancy.

Monte Carlo simulation of release of vesicular content in neuroendocrine cells.

The release of transmitter from the vesicle, its diffusion through the fusion pore, and the cleft and its interaction with the carbon electrode were simulated using the Monte Carlo method. According to the simulation the transmitter release is largely determined by geometric factors--the ratio of the fusion pore cross-sectional and vesicular areas, if the diffusion constant is as in the aqueous solution--but the speed of transmitter dissociation from the gel matrix plays an important role during the rise phase of release. Transmitter is not depleted near the entrance to the fusion pore and there is no cleft-to-vesicle feedback, but the depletion becomes evident if the diffusion constant is reduced, especially if the pore is wide. In general, the time course of amperometric currents closely resembles the time course of the simulated transmitter concentration in the cleft and the time course of release. Surprisingly, even a tenfold change of the electrode efficiency has only a marginal effect on the amplitude or the time course of amperometric currents. Greater electrode efficiency however lowers the cleft concentration, but only if the cleft is narrow. As the cleft widens the current amplitudes diminish and rise times lengthen, but the decay times are less affected. Moreover, the amplitude dependence of the rise and decay times becomes steeper as the cleft widens and/or as the release kinetics slows. Finally, lower diffusion constant of transmitter in the narrow cleft does not further prolong the amperometric currents, whose slow time course reflects slow release kinetics.

Not wisely but too well: aging as a cost of neuroendocrine activity.

Progressive decline of some neuroendocrine signaling systems has long been assumed to cause age-related physiological impairments and limit life span. However, hypophysectomy--removal of the pituitary gland--can delay many aspects of the aging process, and recent genetic studies have confirmed that reducing the secretion of pituitary hormones can increase the life span of laboratory organisms. Most strikingly, reducing activity of the insulin/insulin-like growth factor-1 signaling system substantially increases life span. Conversely, activity of the reproductive system or activation of stress responses can curtail life span. Because caloric restriction also reduces the activity of several neuroendocrine systems while increasing life span, it now appears that the aging process is driven, at least in part, by neuroendocrine activity rather than by its decline with age.

Immunohistochemical assessment of the neurosecretory cells of the chicken thymus using a novel monoclonal antibody against avian chromogranin A.

An immunocytochemical approach to the identification of neuroendocrine cells in the thymus of the chicken was taken based on a novel monoclonal antibody against turkey chromogranin A (CgA), a classic marker protein for neuroendocrine cells. CgA-immunoreactive cells were readily observed in the thymus, and were typically confined to the medullary side of the corticomedullary junction of the thymic lobules. Reversed transcription PCR confirmed local production of CgA in the thymus. The majority of CgA+ cells were small and round or oval in shape but some cells were larger and had conspicuous extensions. Immunofluorescent double staining experiments with antibodies against Neuron-specific enolase and with a neural crest marker (HNK-1) indicated no demonstrable overlap between the CgA-positive cells and either of the above cell populations, demonstrating the existence of three distinct neuronal/neuroendocrine cell populations in the avian thymus.

Assessment of the hypothalamic-pituitary-adrenal axis over a 24-hour diurnal period and in response to neuroendocrine challenges in women with and without childhood sexual abuse and posttraumatic stress disorder.

BACKGROUND: Preclinical studies showed that early stress results in long-term alterations in the hypothalamic-pituitary-adrenal (HPA) axis. We performed a comprehensive assessment of the HPA axis in women with and without a history of early childhood sexual abuse and posttraumatic stress disorder (PTSD). METHODS: Fifty-two women with and without a history of early childhood sexual abuse and PTSD underwent a comprehensive assessment of the HPA axis, including measurement of cortisol in plasma every 15 min over a 24-hour period and cortisol and corticotropin (ACTH) following corticotropin-releasing factor (CRF) and ACTH challenge. RESULTS: Abused women with PTSD had lower levels of cortisol during the afternoon hours (12:00-8:00 PM) of a 24-hour period compared with non-PTSD women. Their ACTH response to a CRF challenge was blunted compared with nonabused non-PTSD (but not abused non-PTSD) women. There were no differences in cortisol response to CRF and ACTH challenges between the groups. Increased PTSD symptom levels were associated with low afternoon cortisol levels. CONCLUSIONS: These findings suggest that early abuse is associated with increased CRF drive as evidenced by decreased pituitary sensitivity to CRF, whereas in abuse with PTSD there is a specific hypocortisolemia that is most pronounced in the afternoon hours.

An overview of computer algorithms for deconvolution-based assessment of in vivo neuroendocrine secretory events.

The availability of increasingly efficient computational systems has made feasible the otherwise burdensome analysis of complex neurobiological data, such as in vivo neuroendocrine glandular secretory activity. Neuroendocrine data sets are typically sparse, noisy and generated by combined processes (such as secretion and metabolic clearance) operating simultaneously over both short and long time spans. The concept of a convolution integral to describe the impact of two or more processes acting jointly has offered an informative mathematical construct with which to dissect (deconvolve) specific quantitative features of in vivo neuroendocrine phenomena. Appropriate computer-based deconvolution algorithms are capable of solving families of 100-300 simultaneous integral equations for a large number of secretion and/or clearance parameters of interest. For example, one application of computer technology allows investigators to deconvolve the number, amplitude and duration of statistically significant underlying secretory episodes of algebraically specifiable waveform and simultaneously estimate subject- and condition-specific neurohormone metabolic clearance rates using all observed data and their experimental variances considered simultaneously. Here, we will provide a definition of selected deconvolution techniques, review their conceptual basis, illustrate their applicability to biological data and discuss new perspectives in the arena of computer-based deconvolution methodologies for evaluating complex biological events.