Corticotropin-releasing hormone (CRH) and catecholamines are suggested to play a significant role in the pathophysiology of depression. In the present study we investigated gene expression of CRH in ...the hypothalamic paraventricular nucleus (PVN) and tyrosine hydroxylase (TH) in the locus coeruleus (LC) in an experimental model of depression. A chronic mild stress model was applied in rats of both genders for a three-week period. Anhedonic behaviour, a typical sign of depression-like state, was measured by a sucrose preference test. The chronic mild stress induced a decrease in sucrose preference in both genders. The body weight gain was reduced in males only. The total activity in the open field test was unchanged, however, male rats exposed to chronic mild stress showed enhanced locomotor activity during the first minute of the session, suggesting increased anxiety. Basal plasma corticosterone levels, thymus and adrenal weights measured on the third day after cessation of the stress regimen, were not affected by the stress procedure. Evaluation of CRH mRNA levels in the PVN by in situ hybridisation revealed a significant rise in response to chronic mild stress in males. In females, the basal CRH mRNA levels were higher compared to those in males, but the stress-induced rise was absent. Chronic mild stress resulted in a decrease in TH mRNA levels in the LC. These data demonstrate that chronic mild stress model of depression induces a specific stress response with a reduction of TH gene expression in the LC and clear gender differences in gain of body weight, anxiety-like behaviour, and CRH mRNA levels in the PVN.
There is some evidence that delta-opioid receptors may be involved in the brain processes related to neuroprotection. The aim of the present studies was to test the hypothesis that endogenous opioid ...peptides acting via delta-opioid receptors can protect against stress-induced changes in factors related to brain plasticity and stress hormone release. Forty male adult Wistar rats were used. Half of the animals were exposed to sustained partial restraint stress (hypokinesis) lasting 48 h. Rats were treated with vehicle (isotonic saline) or the delta-opioid receptor antagonist naltrindole (3 mg/kg/ml, s.c.) six times a day. The stressfulness of the model was confirmed by increased plasma concentrations of corticosterone and prolactin, the increase in anxiety behavior in the open field test, as well as the reduction of BrdU incorporation into newly formed DNA in the hippocampus. Treatment with naltrindole potentiated the stress-induced rise in aldosterone concentrations. The blockade of delta-opioid receptors resulted in a decrease in hippocampal BDNF gene expression independently of control or stress conditions. Treatment with naltrindole enhanced plasma concentrations of copeptin, a stable precursor of vasopressin. In conclusion, these results suggest that endogenous opioid peptides might play an inhibitory role in aldosterone release under stress conditions and in the control of vasopressin release independently of stress exposure. Endogenous opioids might stimulate hippocampal gene expression of the important neurotrophic factor BDNF via delta-opioid receptors.
An altered stress response can contribute to the transition from preclinical psychotic symptoms to the clinical manifestation of schizophrenia and other psychotic disorders. The present study was ...aimed at testing the hypotheses that (i) the autonomic and neuroendocrine responses under psychosocial stress are dysregulated in individuals with high psychosis proneness (schizotypy); (ii) the magnitude of post-stress autonomic activation and cortisol release predicts alterations in semantic memory retrieval. The study was performed in 73 healthy individuals of both sexes with either high or low schizotypal traits preselected out of 609 individuals using the Schizotypal Personality Questionnaire. A psychosocial stress procedure based on public speech was used as a stress model. We found that individuals with high schizotypy engaged in less adaptive emotional stress-coping strategies than low schizotypy individuals. Yet, the neuroendocrine, immune, and sympathetic activation in response to the stress test was not different between the groups. Irrespective of the exposure to the stressor, individuals with high schizotypy were less fluent when retrieving associations from semantic memory. In addition, we demonstrated that acute psychosocial stress reduced the flexibility of semantic memory retrieval. The post-stress mental inflexibility was reliably predicted by the concomitant elevation of cortisol concentrations in saliva. The present study thus brings novel evidence indicating that the acute psychosocial challenge impairs retrieval flexibility in the semantic domain, which may be due to neuroendocrine activation.
•High schizotypy is associated with less adaptive emotional stress-coping strategies.•Stress-induced neuroendocrine changes are not affected by schizotypal traits.•Automatic semantic memory retrieval is compromised in high schizotypy.•The flexibility of semantic memory retrieval is reduced under acute stress.•Post-stress cortisol increase may mediate the inflexibility of semantic retrieval.
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•Testosterone/cortisol ratio positively correlates with prosocial behavior.•Testosterone correlates with assertion depending on high and low stress perception.•Affiliative and flight ...behavior was higher in subjects with high stress perception.
The relationship between hormone release and non-verbal communication under stress conditions is still not sufficiently explored. The aim of the present study was to test the hypothesis that salivary testosterone concentrations and testosterone/cortisol (T/C) ratios correlate positively with assertive behavior representing a non-aggressive form of dominance during an acute stress situation. As a stress model, a socially evaluated cold pressor test was investigated in healthy men. The non-verbal behavior was analyzed according to the ethological coding system for interviews described by Troisi (1999). Salivary testosterone concentrations did not change throughout the stress test. The T/C ratios decreased significantly over time only in subjects showing high stress perception. The duration of affiliative and the frequency of flight behavior was higher in subjects with high stress perception compared to those with low stress perception. A significant positive correlation between the duration of prosocial behavior and values of T/C ratios was found in the whole sample. The area under the curve values of testosterone positively correlated with the duration of assertive behavior in the group with high stress perception and negatively in the other group. Our findings allow suggesting that the changes in non-verbal behavior during acute psychosocial stress situations may be more pronounced in subjects showing high stress perception. Obtained results motivate further research on a better understanding of the consequences of the lack of sense of full facial expressions, such as wearing face masks, on the balance between hormones and non-verbal behavior under stress conditions.
Abstract Evidence is accumulating that aldosterone may exert central actions and influence mental functions. The aim of the present study was to test the hypothesis that major depressive disorder ...affects the diurnal variation of salivary aldosterone and that aldosterone concentrations reflect the duration and severity of the depressive episode in a sex dependent manner. The sample consisted of 60 patients (37 postmenopausal women, 23 men) with major depressive disorder. Patients were examined two times, in acute depressive episode (admission to the hospital) and after reaching clinical remission (discharge). The samples of saliva were taken by the patients themselves twice a day (8.00–9.00 h in the morning and in the evening). Aldosterone concentrations were significantly higher in women compared to men and were significantly higher at the time of admission to the hospital compared to those at the discharge. Morning but not evening salivary aldosterone concentrations reflected the length of the depressive episode in women as well as the severity of the disorder in both sexes. Moreover, the patients with depression failed to exert known daily rhythmicity of aldosterone release. The present study brings several pieces of evidence suggesting the association of aldosterone with the pathophysiology of depression. Salivary aldosterone concentrations appear to reflect the outcome, the duration and the severity of the depressive episode in a sex dependent manner.
Selegiline, also known as L-deprenyl, and (2R)-1-(1-benzofuran-2-yl)-N-propylpentane-2-amine (BPAP) were found to induce enhancement of monoamine neurotransmission in low and very low doses. In ...addition, these enhancers may modify glutamatergic neurotransmission. The aim of the present study was to test the hypothesis that under stress conditions, chronic treatment with enhancer drugs has a positive impact on the glutamatergic system and other parameters related to brain plasticity, stress-related systems, and anxiety behavior. We exposed male Wistar rats to a chronic mild stress procedure combined with chronic treatment with two synthetic enhancer drugs. The gene expression of GluR1, an AMPA receptor subunit was reduced by repeated treatment with deprenyl in the hippocampus and with both BPAP and deprenyl in the prefrontal cortex. A significant reduction of NMDA receptor subunit GluN2B expression was observed in the hippocampus but not in the prefrontal cortex. Deprenyl treatment led to an enhancement of hippocampal BDNFmRNA concentrations in stress-exposed rats. Treatment with enhancer drugs failed to induce significant changes in stress hormone concentrations or anxiety behavior. In conclusion, the present study in chronically stressed rats showed that concomitant treatment with enhancer drugs did not provoke substantial neuroendocrine changes, but modified gene expression of selected parameters associated with brain plasticity. Observed changes may indicate a positive influence of enhancer drugs on brain plasticity, which is important for preventing negative consequences of chronic stress and enhancement of stress resilience. It may be suggested that the changes in glutamate receptor subunits induced by enhancer drugs are brain region-specific and not dose-related.
•Under stress conditions, enhancers modify parameters related to brain plasticity.•Enhancers affect glutamatergic system by reducing GluR1 and GluN2B gene expression.•Enhancers increase the gene expression of BDNF in the hippocampus.•Enhancers do not modify anxiety behavior and stress hormone release.
Highlights • High trait anxiety and unfavorable coping strategy are present in female but not male atopic patients. • Changes in personality traits were associated with altered neuroendocrine ...activation. • Atopic patients exhibited insufficient responses of alpha-amylase and aldosterone during stress. • Menstrual cycle modified alpha-amylase activity in healthy women, but not in patients with atopy.
Post-weaning social isolation has been shown to be a relevant animal model for studying the mechanisms underlying psychopathological states induced by early-life stressful experiences. Besides ...extensively studied brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (TrkB) receptor, increasing attention is being given to a neuropeptide precursor VGF (non-acronymic). Several lines of evidence indicate an interplay between the neurotrophins and nitric oxide signaling. This study investigated the long-term consequences of post-weaning social isolation on behavior, VGF/BDNF/TrkB pathway and two isoforms of nitric oxide synthase (NOS) in the hippocampus and examined whether these effects were sex-specific. Male and female Sprague-Dawley rats were reared either in social isolation or social groups from postnatal day 21 for 9 weeks (n = 12–15/group and sex). Post-weaning social isolation induced impairments in sensorimotor gating and increased anxiety-like behavior in rats of both sexes. These behavioral alterations were accompanied by attenuated gene expression of VGF and TrkB receptor in the hippocampus. Isolation-induced reduction in VGF gene expression was more evident in male isolates. Similar changes were found in neuronal NOS (nNOS) gene expression with reduced mRNA levels in male isolates. Gene expression of BDNF and inducible NOS was not influenced by isolation rearing or sex. In addition, sex-specific patterns of VGF and nNOS gene expression in the hippocampus with higher mRNA levels in males than in females were revealed. The present study demonstrates a relationship between nNOS, VGF, BDNF, and TrkB confirming a link between nitric oxide and neurotrophins signaling pathways. Our findings indicate that long-term post-weaning social isolation alters signaling via VGF/BDNF/TrkB and nNOS that could interfere with neurodevelopmental processes which may contribute to pathological behavioral symptoms in adulthood. Future studies are needed to support this suggestion since the direct mechanistic link has not been approached in this study.
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•Post-weaning social isolation reduces signaling via VGF/BDNF/TrkB pathway.•Isolation rearing reduces hippocampal neuronal nitric oxide synthase (nNOS) mRNA levels.•Isolation-induced reduction in VGF and nNOS mRNA levels is more evident in male isolates.•Sex-specific patterns of VGF and nNOS gene expression do exist.•Isolation rearing induces deficit in prepulse inhibition and anxious phenotype.
Patients with atopy were found to exhibit blunted cortisol responses to acute stress stimuli. The aim of this study was to test the hypothesis that cumulative cortisol concentrations in the hair of ...patients with atopy are lower than in healthy subjects when related to their perceived stress experience. The sample consisted of 31 participants. The most proximal 3 cm of hair (as close to the scalp as possible), reflecting the cumulative cortisol secretion during the previous 3 months, was used for the analysis. Only in 20 subjects (9 patients with atopy and 11 healthy controls), there was a sufficient amount of hair for precise analysis using a new methodology. The results showed lower hair cortisol concentrations in patients with atopy compared to those in controls. The perceived stress scores in patients with atopy and healthy controls were not statistically different. The cortisol concentration/perceived stress score ratios were lower in patients with atopy compared to those in controls. No statistically significant correlation between hair cortisol and long-term experienced stress assessed via perceived stress scale was observed. In conclusion, the cumulative cortisol secretion in the hair of atopic patients is lower than would be expected according to their subjective scores of perceived stress. Most importantly, the previously lower stress hormone increase found in acute stress situations and in children now was confirmed in adult patients with chronic stress load.
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Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
1. Glutamatergic mechanisms are thought to be involved in stress-induced alterations of brain function, especially in the hippocampus. We have hypothesized that repeated stress exposure may evoke ...changes of hippocampal glutamate receptors at the level of gene expression. 2. The study was designed to analyze the levels of mRNA coding for NMDAR1, the essential subunit of the N-methyl-D-aspartate (NMDA) receptor subtype, and for GluR1, an AMPA glutamate receptor subunit, after repeated immobilization stress in rat hippocampus. Toward this aim, we applied a competitive RT-PCR technique which allowed precise and reliable quantification of the transcripts. 3. We found that repeated immobilization stress for 7 days significantly increased GluR1 mRNA levels, by 27% (P<0.01), as measured 24 hr after the last stress exposure. Levels of mRNA coding for NMDAR1 were slightly elevated, but the difference failed to be significant. 4. These results demonstrate selective changes in the gene expression of glutamate receptor subunits, which are likely to take part in the mechanisms leading to enhanced excitability and vulnerability of hippocampal neurons and to potential damage during repeated or chronic stress exposure.
