Period Of Chronic Stress Research Articles

Beneficial and Adverse Consequences of Increased Brain Plasticity: the Interplay Among Serotonin, Susceptibility to the Environment and Depression

Antidepressants represent the standard treatment for major depression. However, their efficacy is variable and incomplete. A growing number of studies suggest that the environment plays a major role in determining the efficacy of these drugs, specifically of selective serotonin reuptake inhibitors (SSRI). We recently hypothesized that the increase in serotonin levels induced by SSRI may not affect mood per se , but enhance neural plasticity and, consequently, renders the individual more susceptible to the environment. Thus, SSRI administration in a favorable environment would lead to a reduction of symptoms, while in a stressful environment might lead to a worse prognosis. To test this hypothesis, we treated C57BL/6 adult male mice with chronic fluoxetine while exposing them to either (i) an enriched environment, after exposure to a chronic stress period aimed at inducing a depression-like phenotype, or (ii) a stressful environment. A wide number of molecular, cellular and behavioral endpoints considered endophenotypes of depression were investigated. These include long-term potentiation, BDNF levels, hypothalamic-pituitary-axis activity, neurogenesis, anhedonia and optimistic attitude (cognitive bias). Mice treated with fluoxetine in an enriched condition improved their depression-like phenotype compared to controls, displaying an overall reduction of all endophenotypes of depression investigated. By contrast, when chronic fluoxetine administration occurred in a stressful condition, mice showed a more distinct worsening of the depression-like profile. Our findings suggest that the effect of SSRI on depression-like phenotypes in mice is not determined by the drug per se but is induced by the drug and driven by the environment. These findings may be helpful to explain variable effects of SSRI found in clinical practice and to device strategies aimed at enhancing their efficacy by means of controlling environmental conditions.

Antidepressant treatment outcome depends on the quality of the living environment: a pre-clinical investigation in mice.

Antidepressants represent the standard treatment for major depression. However, their efficacy is variable and incomplete. A growing number of studies suggest that the environment plays a major role in determining the efficacy of these drugs, specifically of selective serotonin reuptake inhibitors (SSRI). A recent hypothesis posits that the increase in serotonin levels induced by SSRI may not affect mood per se, but enhances neural plasticity and, consequently, renders the individual more susceptible to the influence of the environment. Thus, SSRI administration in a favorable environment would lead to a reduction of symptoms, while in a stressful environment might lead to a worse prognosis. To test this hypothesis, we treated C57BL/6 adult male mice with chronic fluoxetine while exposing them to either (i) an enriched environment, after exposure to a chronic stress period aimed at inducing a depression-like phenotype, or (ii) a stressful environment. Anhedonia, brain BDNF and circulating corticosterone levels, considered endophenotypes of depression, were investigated. Mice treated with fluoxetine in an enriched condition improved their depression-like phenotype compared to controls, displaying higher saccharin preference, higher brain BDNF levels and reduced corticosterone levels. By contrast, when chronic fluoxetine administration occurred in a stressful condition, mice showed a more distinct worsening of the depression-like profile, displaying a faster decrease of saccharin preference, lower brain BDNF levels and increased corticosterone levels. Our findings suggest that the effect of SSRI on depression-like phenotypes in mice is not determined by the drug per se but is induced by the drug and driven by the environment. These findings may be helpful to explain variable effects of SSRI found in clinical practice and to device strategies aimed at enhancing their efficacy by means of controlling environmental conditions.

Allopregnanolone regulates neurogenesis and depressive/anxiety-like behaviour in a social isolation rodent model of chronic stress

Chronic stress has been implicated as a causal factor in depression and anxiety, and is associated with neuroendocrine dysfunction and impaired hippocampal neurogenesis. The neurosteroid allopregnanolone (3α,5α-THP; ALLO) has been shown to be reduced in depressed patients. ALLO is “stress responsive” and plays a major role in regulating hypothalamic-pituitary-adrenal (HPA) axis function. We propose that reduced ALLO levels following chronic stress leads to HPA hyperactivity due to diminished ALLO regulation. This will result in increased glucocorticoid levels and reduced BDNF expression, leading to impaired hippocampal neurogenesis and the precipitation of depression/anxiety. To investigate this, chronic stress was induced using the social isolation model and depressive/anxiety-like behaviour assessed using the novelty-suppressed feeding test and forced-swim test. The social isolation model was associated with a significant reduction in endogenous ALLO levels and a depressive/anxiety-like behavioural profile. When exogenous ALLO was administered from the onset of isolation it prevented the development of depressive/anxiety-like behaviours and impairment of hippocampal neurogenesis. When treatment was initiated following six weeks of social isolation, behavioural profile was restored and deficits in BDNF and neurogenesis were not observed. Supporting our hypothesis we observed that socially isolated animals exhibited reduced HPA responsiveness, which was either prevented or normalised with ALLO treatment. Combined, these results indicate that administration of exogenous ALLO either during or following a period of chronic stress can prevent or normalise HPA dysfunction and impairment of hippocampal neurogenesis respectively, precluding the establishment of depressive/anxiety-like behaviours. ALLO may therefore provide a novel therapeutic target for the treatment of depression/anxiety.

Aldosterone Acts in the Nucleus of the Solitary Tract to Alter Stress Responsiveness

Aldosterone (aldo) acts at brain mineralocorticoid receptors (MR) to increase arterial pressure. We hypothesized that activation of MR selectively within the Nucleus Tractus Solitarius (NTS), a key circulatory control center, would enhance the cardiovascular response restraint stress. Mean arterial pressure (MAP) was measured by radiotelemetry in adult male Sprague–Dawley rats. Chronic elevations in aldo levels within the NTS were achieved by implanting pellets of 1% aldo over the NTS (n=4). Sham pellets were made of silastic (n=4). All rats were subjected to 60 min of restraint stress daily for 11 days. On day 12 they were exposed to a novel stress by placing them in 1 cm of room temp water for 15 min. Aldo did not alter baseline MAP. Aldo attenuated the integrated MAP response to restraint stress on the first day (990±50 mmHg/60 min vs 1510± 82 mmHg/60 min, aldo vs sham, P=0.002). The MAP response to the final restraint stress was not significantly affected by aldo. With water stress, the integrated MAP response was enhanced in the aldo‐ vs. the sham‐treated rats (416±14 mmHg/15 min vs. 332±32 mmHg/15 min, P=0.054). Compared with the sham rats, the aldo‐treated rats gained less weight during the period of chronic stress (2±5 gm, n=4 vs. 24±7 gm, n=3, P=0.04). We conclude that aldosterone acts in the NTS to influence stress responsiveness. Support: NIH#HL 076807, AHA#GRNT 4460047.

Gratitude when it is needed most: Social functions of gratitude in women with metastatic breast cancer.

Theory and evidence suggest that everyday positive emotions may be potent factors in resilience during periods of chronic stress, yet the body of evidence is scant. Even less research focuses on the adaptive functions of specific positive emotions in this critical context. In the current research, 54 women with metastatic breast cancer provided information about their emotional responses to benefits received to test hypotheses regarding the social functions of gratitude. One set of analyses provide support for the hypothesized role of ego-transcendence in feeling gratitude upon receipt of a benefit from another person. As predicted, in a second set of analyses, grateful responding to received benefits predicted an increase in perceived social support over three months only for women low in ambivalence over emotional expression. These findings add to evidence regarding the social causes and consequences of gratitude, supporting a view of gratitude as an other-focused positive emotion that functions to promote high-quality relationships. Discussion focuses on the chronically stressful context as an important testing ground for theory on gratitude and other positive emotions.

Opposing effects of chronic stress and weight restriction on cardiovascular, neuroendocrine and metabolic function

Chronic stress is associated with dysregulation of energy homeostasis, but the link between the two is largely unknown. For most rodents, periods of chronic stress reduce weight gain. We hypothesized that these reductions in weight are an additional homeostatic challenge, contributing to the chronic stress syndrome. Experiment #1 examined cardiovascular responsivity following exposure to prolonged intermittent stress. We used radio-telemetry to monitor mean arterial pressure and heart rate in freely moving, conscious rats. Three groups of animals were tested: chronic variable stress (CVS), weight-matched (WM), and controls. Using this design, we can distinguish between effects due to stress and effects due to the changing body weight. WM, but not CVS, markedly reduced basal heart rate. Although an acute stress challenge elicited similar peak heart rate, WM expedited the recovery to baseline heart rate. The data suggest that CVS prevents the weight-induced attenuation of cardiovascular stress reactivity. Experiment #2 investigated hypothalamic-pituitary-adrenal axis and metabolic hormone reactivity to novel psychogenic stress. WM increased corticosterone area under the curve. CVS blunted plasma glucose, leptin, and insulin levels in response to restraint. Experiment #3 tested the effects of WM and CVS on PVN oxytocin and corticotrophin-releasing hormone mRNA expression. CVS increased, while WM reduced PVN CRH mRNA expression, whereas both CVS and WM reduced dorsal parvocellular PVN oxytocin mRNA. Overall, the data suggest that weight loss is unlikely to account for the deleterious effects of chronic stress on the organism, but in fact produces beneficial effects that are effectively absent or indeed, reversed in the face of chronic stress exposure.

Multivitamin–Mineral and Vitamins (E + C) Supplementation Modulate Chronic Unpredictable Stress-Induced Oxidative Damage in Brain and Heart of Mice

Brain is a target of stress along with the immune, metabolic, and cardiovascular systems of the body. In the present work, the preventive roles of a multivitamin-mineral supplement and vitamins (E + C) in chronic unpredictable stress (CUS)-induced oxidative damage were studied in the brain and heart of Swiss albino mice. Thirty-two mice were randomized to one of the following groups: control + vehicle, CUS + vehicle, CUS + multivitamin-mineral, and CUS + vitamins (E + C). CUS was applied for 4weeks, and multivitamin-mineral and vitamins (E + C) were administered orally for the same period. CUS led to a negative impact on all the biochemical parameters analyzed. Elevation in malondialdehyde and reduction in glutathione levels were found. The activities of superoxide dismutase, catalase, glutathione S-transferase, and glutathione reductase were decreased. Treatment with multivitamin-mineral and vitamins (E + C) brought these parameters to near normal levels. Multivitamin-mineral was found more restitutive than combined vitamins (E + C) doses. The present study hypothesizes that supplementation with a multivitamin-mineral may prove more effective than vitamin treatment alone in the alleviation of oxidative damage in brain and heart during periods of chronic stress.

This Issue: Brain–Body Interactions: How Mental Processes and Psychiatric Illness Affect Medical Outcomes

Mental processes and psychiatric illness have significant, measurable effects on the course and outcome of medical conditions. The cause of this phenomenon is that the brain continuously integrates internal and external information and adjusts the body’s physiological processes to meet expected challenges. Although the adjustments directed by the brain are genetically programmed to be adaptive, under certain conditions they can have deleterious effects. For example, the neuroplastic changes precipitated by periods of chronic stress, such as childhood abuse or military combat, can have adverse physiological consequences that last a lifetime. In addition, as the articles in this issue document, comorbid psychiatric illnesses have a significant effect on the treatment costs and outcomes of a variety of medical conditions.

Chronic but not acute foot-shock stress leads to temporary suppression of cell proliferation in rat hippocampus

Stressful experiences, especially when prolonged and severe are associated with psychopathology and impaired neuronal plasticity. Among other effects on the brain, stress has been shown to negatively regulate hippocampal neurogenesis, and this effect is considered to be exerted via glucocorticoids. Here, we sought to determine the temporal dynamics of changes in hippocampal neurogenesis after acute and chronic exposure to foot-shock stress. Rats subjected to a foot-shock procedure showed strong activation of the hypothalamic–pituitary–adrenal (HPA) axis, even after exposure to daily stress for 3 weeks. Despite a robust release of corticosterone, acute foot-shock stress did not affect the rate of hippocampal cell proliferation. In contrast, exposure to foot-shock stress daily for 3 weeks led to reduced cell proliferation 2 hours after the stress procedure. Interestingly, this stress-induced effect did not persist and was no longer detected 24 hours later. Also, while chronic foot-shock stress had no impact on survival of hippocampal cells that were born before the stress procedure, it led to a decreased number of doublecortin-positive granule neurons that were born during the chronic stress period. Thus, whereas a strong activation of the HPA axis during acute foot-shock stress is not sufficient to reduce hippocampal cell proliferation, repeated exposure to stressful stimuli for prolonged period of time ultimately results in dysregulated neurogenesis. In sum, this study supports the notion that chronic stress may lead to cumulative changes in the brain that are not seen after acute stress. Such changes may indicate compromised brain plasticity and increased vulnerability to neuropathology.

The effects of stress on food choice, mood and bodyweight in healthy women

Summary This paper examines the effects of stress on the neuroendocrine production of cortisol and links this to potential changes in food choice, mood and bodyweight. Animal and human studies suggest that stressful conditions can result in low mood, increased energy intake, particularly from fatty acids and non‐milk extrinsic sugars (NMES), and potential changes in bodyweight. With current unsustainable rises in obesity in the Western world, tackling predictors of weight increase remains a primary target for intervention. In a longitudinal naturalistic study of 71 healthy women, we found an increase in cortisol secretion during a period of chronic stress to be strongly correlated with changes in food choice and increased energy consumption, as well as an increase in intake of saturated fatty acids and NMES. This resulted in an increase in bodyweight. We also found that anxiety and depression increased significantly during the stress period; however, we could find no correlation with mood, food choice or energy intake. Furthermore, we found that women with a body mass index (BMI) on the higher side of ‘healthy’, who experienced a significant increase in cortisol secretion under chronic stress, were more vulnerable to increases in bodyweight than women with lower BMIs and a smaller increase in cortisol secretion. Further research is needed to investigate whether cognitive behavioural/remedial therapies to reduce the impact of stress can help to minimise changes in diet, bodyweight and mental health.

Long-term behavioral and neuroendocrine alterations following chronic social stress in mice: Implications for stress-related disorders

The period of adolescence is characterized by a high vulnerability to stress and trauma, which might result in long-lasting consequences and an increased risk to develop psychiatric disorders. Using a recently developed mouse model for chronic social stress during adolescence, we studied persistent neuroendocrine and behavioral effects of chronic social stress obtained 12 months after cessation of the stressor. As a reference, we investigated immediate effects of chronic stress exposure obtained at the end of the chronic stress period. Immediately after the 7 week chronic stress period stressed animals show significantly increased adrenal weights, decreased thymus weight, increased basal corticosterone secretion and a flattened circadian rhythm. Furthermore, stressed animals display an increased anxiety-like behavior in the elevated plus maze and the novelty-induced suppression of feeding test. Hippocampal mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR) mRNA levels were significantly decreased. To investigate persistent consequences of this early stressful experience, the same parameters were assessed in aged mice 12 months after the cessation of the stressor. Interestingly, we still found differences between formerly stressed and control mice in important stress-related parameters. MR expression levels were significantly lower in stressed animals, suggesting lasting, possibly epigenetic alterations in gene expression regulation. Furthermore, we observed long-term behavioral alterations in animals stressed during adolescence. Thus, we could demonstrate that chronic stress exposure during a crucial developmental time period results in long-term, persistent effects on physiological and behavioral parameters throughout life, which may contribute to an enhanced vulnerability to stress-induced diseases.

The effect of chronic psychological stress on corticosterone, plasma metabolites, and immune responsiveness in European starlings

Although increases in glucocorticoid concentrations during acute stress are believed to help animals survive stressful events, chronic changes in glucocorticoid concentrations can alter metabolism and lead to disease. We studied the effect of chronic psychological stress on corticosterone (CORT), corticosterone binding globulin (CBG), glucose, and triglyceride concentrations as well as immune responsiveness to a T-cell mitogen challenge in European starlings, Sturnus vulgaris. To induce chronic stress we used a chronic stress protocol consisting of five stressors (loud radio, cage tapping, cage rolling, human voice, and bag restraint) administered in random order for 30 min for 4 times/day over 18 days. Total CORT decreased throughout the chronic stress period, which parallels a previous study with starlings. CBG capacity did not significantly change with chronic stress, thus free CORT followed the same pattern of attenuation as total CORT during chronic stress. Despite the change in regulation of CORT release, daytime glucose and triglyceride concentrations did not change with chronic stress. In addition, immune responsiveness in chronically stressed and unstressed birds was similar. Our results, together with a previous study using a similar CSP in European starlings, suggest that starlings physiologically dampen the HPA axis during chronic psychological stress to avoid pathology associated with chronically augmented CORT concentrations such as hyperglycemia and impaired immune function.

Effect of coping on endocrinoimmune functions in different stress situations

The objective of this study was to examine the effects of coping strategies on the endocrine and immune functions in different stress situations. Thirty-eight medical students were enrolled in this study. Cell-mediated immune function was measured using the lymphocyte proliferative response to phytohemagglutinin (PHA) and interleukin-2 (IL-2) production during the nonexamination period and during the preexamination period. Endocrine functions were assessed by measuring the plasma levels of norepinephrine, adrenocorticotropic hormone (ACTH) and cortisol. The Global Assessment of Recent Stress (GARS) scale, the Stress Response Inventory, the anxiety, depression, and somatization subscales of the Symptom Checklist-90-revised, the Way of Coping-revised, the Toronto Alexithymia Scale and the Anger Expression Scale were used as psychometric measures. The subjects with higher levels of total GARS scores showed significantly higher IL-2 production during the nonexam period than those with lower levels of total GARS scores. During the same period, IL-2 production in the less positive reappraisal group was significantly higher than in the more positive reappraisal group. Lymphocyte proliferation in the group seeking less social support was also significantly higher than in the group seeking more social support. However, no significant association was found between the coping strategies and each of the hormone levels. These results suggest that positive reappraisal and seeking social support can be associated with the alteration of immune function during a chronic stress period. In particular, positive reappraisal is likely to reverse the stress-induced immune responses. This study did not find that neuroendocrine function such as the sympathetic-adrenal medullary axis or the hypothalamic–pituitary–adrenal axis is playing a mediating role in the relationship between coping and immunity.

Previous chronic stress does not alter the cortisol response to an additional acute stressor in jundiá ( Rhamdia quelen, Quoy and Gaimard) fingerlings

Lately, a considerable amount of work has been carried out on fish response to acute and chronic stress. However, very few studies have been attempted to ascertain the effects of combined stressors. In fish, the larviculture is a critical period because the practices employed in this phase are able to provoke a characteristic stress response, which may have chronic characteristics, and may impair further responses to acute stress. In the experiment reported herein, 120-day-old, mixed-sex jundiá fingerlings were used to study the ability of jundiá to cope with a combination of chronic and acute stress. Two hundred and forty fingerlings were evenly distributed in six 2000-L concrete tanks. In three of the six tanks, the fish were exposed to chronic stress, provoked by daily soft handling in spatial restriction, during a period of 20 days. Following this, at the 21st day, the fingerlings were submitted to acute stress by holding them in a dipnet, out of water for 60 s. In the other three tanks, during the first 20 days, the fish were maintained without any disturbance and were exposed to the same acute stressor, on the 21st day, as the other groups. The aerial exposure provoked a characteristic acute stress response in both groups, with plasma cortisol peak reaching 130 ng/ml 1 h after the acute stressor. The capacity of jundiá to respond to an acute stress stimulus was maintained even for those fish chronically stressed. In the non-stressed group of fish, the acute response occurred with the same pattern, with values similar to those observed in chronically stressed fish. The similarity between the secretion pattern of cortisol in both chronically stressed and unstressed jundiá fingerlings strongly suggests that the occurrence of a period of chronic stress did not impair the capacity of the HPI axis to respond to a further acute stressors. Thus, the results of the present study show that jundiá fingerlings are capable of responding to acute stress even following a chronic period of stress.

P.2.d.011 Effects of the novel antidepressant agomelatine (S 20098) and fluoxetine in chronically stressed tree shrews, an animal model of depression

Social stress is known to be involved in the etiology of central nervous disorders such as depression. In recent years, animal models have been developed that use chronic stress to induce neuroendocrine and central nervous changes that might be similar to those occurring in the course of the development of depressive disorders. The present review gives a summary of observations made in the tree shrew chronic social stress model. During periods of daily social stress, male tree shrews develop symptoms that are known from many depressed patients such as persistent hyperactivities of both the hypothalamic–pituitary–adrenal (HPA) axis and sympathetic nervous system, disturbances in sleeping patterns, and reduced motor activity. Moreover, various physiological parameters indicate an acceleration of the over all metabolic rate in socially stressed tree shrews. Some of these parameters can be renormalized by antidepressants thus supporting the view of the tree shrew social stress paradigm as model for major depression. In the brains of socially stressed animals, monoamine receptors show dynamic changes that reflect adaptation to the persistent monoaminergic hyperactivity during periods of chronic stress. In addition to the changes in neurotransmitter systems, there are structural changes in neurons, e.g., retraction of the dendrites of hippocampal pyramidal neurons. Together, these processes are suggested as a cause of behavioral alterations that can be counteracted by antidepressants in this naturalistic social stress model.

The Alpha-2B Adrenoceptor in the Paraventricular Thalamic Nucleus is Persistently Upregulated by Chronic Psychosocial Stress

Stress has been reported to regulate adrenergic receptors but it is not known whether it has an impact on the alpha-2 adrenoceptor subtype B that is strongly expressed in distinct nuclei of the thalamus. So far little is known about effects of stress on the thalamus. Using the chronic psychosocial stress paradigm in male tree shrews, we analyzed alpha-2B adrenoceptor expression in the paraventricular and the anteroventral nucleus of the thalamus after a six-week period of daily social stress and after a 10-day post-stress recovery period. In situ hybridization with a specific alpha-2B adrenoceptor probe was performed to quantify receptor gene expression in single neurons, and receptor binding was determined by in vitro receptor autoradiography using the radioligand [3H]RX821002. To determine the stress level in the animals, we measured urinary cortisol excretion and body weight. In the neurons of the paraventricular thalamic nucleus, expression of the alpha-2B adrenoceptor transcript was increased after both the six-week chronic-stress period and the post-stress recovery period. Combination of in situ hybridization and immunocytochemistry revealed expression of alpha-2B adrenoceptor transcript in neurons that were stained with an antibody against glutamate but not in neurons immunoreactive for GABA. Alpha-2 adrenoceptor radioligand binding was also increased after both time periods in the paraventricular thalamic nucleus. No significant effects of stress and recovery were observed in the anteroventral thalamic nucleus. Urinary cortisol excretion was increased during the stress period but normalized thereafter. Body weight was reduced during weeks 1 to 3 of stress and then normalized. These data show that long-term chronic psychosocial stress has an impact on alpha-2B adrenoceptor expression in the thalamus and that the effect persists throughout a post-stress recovery period though activity of the hypothalamic pituitary adrenal axis normalizes after stress. Upregulation of the receptor probably alters neurotransmission in the paraventricular thalamic nucleus and may thus influence information transfer to limbic and cortical brain areas.

Comparison of freshwater and marine performances of all-female diploid and triploid Atlantic salmon (Salmo salar L.)

The performance of all-female diploid (AF2N) and triploid (AF3N) Atlantic salmon were compared in fresh water, under commercial production conditions in 1995 and 1996 year classes. The performance of the 1996 year class was also assessed for 14 months in a commercial sea farm. Freshwater mortality was higher in the triploid groups. The majority of losses occurred in the early stages of egg development and during the first feeding period, when the incidence of non-feeding fry was consistently higher. In growth studies, although diploid fry were significantly heavier during first feeding there were no significant differences in weight between groups some 8 months after fertilization or in presmolt growth periods from February to April in 1996 and 1997. Smolting rates were high (range 93.5–95.3%) and the incidence of deformities was low (< 1%) in both groups. Marine survival was lower in the triploid group, largely as a consequence of higher losses sustained during a period of chronic stress, when triploid losses were 9% higher. Growth patterns were similar for the first 11 months in sea water. Although graded triploid salmon were heavier in January 1998 (AF3N 1.62 ± 0.033 kg, AF2N 1.46 ± 0.36 kg, P < 0.05), when the fish were harvested in May 1998 diploid salmon were significantly heavier than triploid salmon although there was no significant difference in weights after evisceration (AF3N 2.40 kg ± 0.04 AF2N 2.49 kg ±0.03). The increase in weight of the diploids between winter and harvest reflects the growth spurt that occurs in maturing fish in the spring. Overall yields of triploid salmon in salt water were lower as a result of inferior survival.

Oligohydramnios at term and pregnancy outcome

An assessment of amniotic fluid volume has become an important component of antenatal testing for the at-risk pregnancy. The presence of normal amniotic fluid volume, either in association with a reactive nonstress test or as a component of the biophysical profile is considered to reflect current fetal well being and probable absence of chronic stress. The chronically stressed fetus is likely to have low amniotic fluid volume because of the shunting of blood preferentially to the brain, heart and adrenal glands at the expense of other body systems during the period of chronic stress. Decreased renal blood flow leads to decreased urinary output. Because the primary component of amniotic fluid in the third trimester of pregnancy is fetal urine, ongoing chronic stress can be recognised as oligohydramnios.Precise amniotic fluid volume (AFV) measurement is accomplished either by use of a dye-dilution technique or by direct measurement of the fluid volume at the time of caesarean delivery. The need for laboratory support and the inherent invasiveness of dye-dilution procedures limits their application to study protocols. Direct measurement of AFV at caesarean delivery is reflective only of fluid volume at the time of delivery and cannot be used to serially evaluate fluid volume as a component of antenatal testing.

Chronic intermittent stress does not differentially alter brain corticosteroid receptor densities in rats prenatally exposed to ethanol

Prenatal ethanol exposure produces hypothalamic-pituitary-adrenal (HPA) hyperresponsiveness to stressors. The present study tested the hypothesis that decreased corticosteroid receptor densities at HPA feedback sites may play a role in deficient feedback inhibition and the resultant HPA hyperresponsiveness that is observed following prenatal ethanol exposure. Brains of adult Sprague-Dawley rats from prenatal ethanol (E), pair-fed (PF) and ad libitum-fed control (C) treatment groups were examined for both mineralocorticoid receptor (MR; Type I) and glucocorticoid receptor (GR; Type II) densities using a cytosolic binding assay. Experiment 1 compared the effects of chronic intermittent stress (Stress Regimen I) and corticosterone (CORT) pellet implants on hippocampal corticosteroid receptor densities in control rats. Experiment 2 determined whether exposure to Stress Regimen I would differentially downregulate and whether adrenalectomy (ADX) would differentially upregulate hippocampal corticosteroid receptors in E compared with PF and C animals. Experiment 3 examined the effects of a modified chronic intermittent stress regimen (Stress Regimen II) on corticosteroid receptor densities at several HPA feedback sites (hippocampus, prefrontal cortex, hypothalamus, and anterior pituitary) in E compared with PF and C animals. CORT pellet implants significantly downregulated hippocampal GR and MR densities in control males and females. Exposure to Stress Regimen I produced downregulation of hippocampal GRs and MRs in males comparable with that produced with CORT pellet implants, and significant downregulation of hippocampal GRs in females across all prenatal treatment groups. This stress regimen also elevated basal plasma CORT levels without concurrent changes in plasma CBG levels, and increased relative adrenal weights in both males and females. In addition, upregulation of hippocampal GRs occurred at 7 days compared with 24 h following ADX in females that had previously been exposed to this stress regimen. Following exposure to Stress Regimen II, both the downregulation of hippocampal corticosteroid receptors and the increase in basal CORT levels in males and females appear to have been abolished by the changes in housing condition during the period of chronic stress. Importantly, prenatal ethanol exposure did not differentially alter GR or MR densities at any feedback site under non-stressed conditions. Exposure to Stress Regimen II, revealed subtle effects of prenatal treatments on hippocampal GRs however it is unlikely that these changes in corticosteroid receptor densities mediated the feedback inhibition deficits observed in E animals. Together, these data demonstrate that: (1) a relatively mild intermittent stress regimen can increase basal CORT levels and downregulate hippocampal corticosteroid receptor densities (2) a seemingly small change in housing conditions during stress appears to eliminate both receptor downregulation and increase in basal CORT levels and (3) decreased corticosteroid receptor densities at HPA feedback sites in the brain do not appear to underlie the HPA hyperresponsiveness observed in E animals.

The relationship between salivary secretory immunoglobulin A and cortisol: neuroendocrine response to awakening and the diurnal cycle

The level of secretory immunoglobulin A (sIgA) measured in saliva is downregulated during periods of chronic stress. In contrast, the response to an acute stress challenge is a transient increase. The process of awakening is associated with stress neuroendocrine activation characterised by increases in salivary cortisol. We therefore examined if this period of hypothalamic–pituitary–adrenal (HPA) activation was associated with changes in salivary sIgA. Associations of sIgA with the diurnal cortisol cycle were also investigated in a separate study. The awakening cortisol response was measured in 30 healthy day-active young adults. There was a marked elevation from the first awakening level over the succeeding 30 min. SIgA showed the opposite response with a marked fall from the highest first awakening concentration in the same samples over the same period. The cortisol rise was significantly correlated with the sIgA fall ( r=0.42). Salivary sIgA showed a similar diurnal cycle to cortisol in a study on eight healthy young adults. An early morning acrophase was followed by a decline to a stable base some 6 h after awakening. The physiological significance of these relationships and possible implications for vulnerability to infection are discussed.