Social defeat stress affects behavior and changes the expression of the genes underlying neuronal plasticity in the brain. The circadian clock regulates most neuronal processes in the brain, which results in daily variations of complex behavior, and any disturbance in circadian clock oscillations increases the risk of mood and cognitive disbalance. In this study, we assessed the effect of acute and repeated social defeat stress on Per2 and Nr1d1 expression in prefrontal cortexes, hippocampi, pineal glands, olfactory bulbs, cerebella, and pituitary glands. We also evaluated the effect of our experimental setting on levels of Bdnf and plasma corticosterone, two markers widely used to asses the impact of stress on mammalian physiology. Our data show that single and repeated social defeat stress upregulates the expression of both clock genes and Bdnf in all brain structures, and corticosterone in the blood. While the general pattern of Bdnf upregulation suggests higher sensitivity in the intruder group, the clock genes are induced more significantly in residents, especially by repeated stress sessions. Our work thus suggests that the model of stress-induced anxiety and depression should consider a group of residents because, for some parameters, they may respond more distinctively than intruders.LAY SUMMARYThe resident/intruder experimental paradigm affects the expression of clock genes Per2, Nr1d1and Bdnf in the brain structures and plasma corticosterone level. The induction of clock genes is evident in both experimental groups; however, it is more marked in residents. Together with the significant increase in Bdnf levels in the majority of brain structures and plasma corticosterone in residents, our data suggest that in the model of social defeat stress, the utility of an experimental group of residents could be contributive.
- MeSH
- kortikosteron MeSH
- mozek metabolismus MeSH
- mozkový neurotrofický faktor * genetika metabolismus MeSH
- potkani Wistar MeSH
- proteiny CLOCK * genetika metabolismus MeSH
- psychický stres * genetika MeSH
- sociální chování MeSH
- sociální porážka MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Fischer 344 (F344) rats are characterized by the hyper-reactive hypothalamic-pituitary-adrenal axis to stressful stimuli, while Lewis (LEW) rats are considered to be hypo-reactive. We studied stress-induced cardiovascular, neuroendocrine, and behavioral responses of adult male F344 and LEW rats subjected to the single (120 min) or the repeated restraint stress (daily 120 min for 1 week). Mean arterial pressure (MAP) and heart rate (HR) were measured in the restrained rats (n = 7-8 for each group) via a catheter inserted into the femoral artery. Baroreceptor sensitivity was evaluated using NO donor sodium nitroprusside and α1-adrenoceptor agonist phenylephrine. The plasma levels of adrenocorticotropic hormone (ACTH), corticosterone, aldosterone, and adrenaline were determined before and during the restraint. Exploratory behavior was tested in open field test. F344 rats exerted the augmented stress-induced increase in plasma ACTH, corticosterone, and adrenaline as well as the impaired endocrine adaptation to the repeated stress compared to LEW rats. F344 rats exhibited higher MAP than LEW rats during single and repeated restraint. Moreover, repeatedly restrained F344 showed elevated HR and diminished baroreflex sensitivity. F344 and LEW rats exhibited similar total locomotor activity and the time spent in the center of open field arena, both parameters being decreased by the repeated restraint. The detailed analysis revealed altered pattern of locomotor behavior in F344 rats subjected to repeated restraint. In conclusion, F344 rats showed the impaired endocrine adaptation that resulted in allostatic overload, which might contribute to the impaired cardiovascular and behavioral adaptation to chronic stress observed in this strain. Lay summary F344 rats, characterized by HPA axis hyper-reactivity, exhibited higher blood pressure during restraint than LEW rats. Moreover, repeatedly restrained F344 rats showed elevated heart rate and impaired baroreflex sensitivity. It can be concluded that a poor adaptation to the repeated stress in F344 rats is not only limited to the neuroendocrine response but also has important cardiovascular consequences.
- MeSH
- fyzické omezení MeSH
- kortikosteron MeSH
- krysa rodu rattus MeSH
- potkani inbrední F344 MeSH
- potkani inbrední LEW MeSH
- psychický stres MeSH
- systém hypofýza - nadledviny * MeSH
- systém hypotalamus-hypofýza * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The hypothalamic-pituitary-adrenal (HPA) axis represents an important and evolutionarily ancient biological pathway linking physical and psychological stressors with human health. Despite considerable research exploring the physiological stress response among developed populations, few studies have examined HPA activity in non-industrialized contexts, restricting understanding of variation in human stress reactivity across global socio-ecological diversity. The present study addresses this shortcoming by investigating diurnal cortisol rhythms among Garisakang forager-horticulturalists of remote, lowland Papua New Guinea. Using a large sample of repeated salivary cortisol measurements from 169 participants (age 4-70 years), multilevel growth curve models were constructed to assess Garisakang waking cortisol concentrations and diurnal cortisol slopes. As predicted, results demonstrate identifiable but substantially diminished diurnal cortisol rhythms relative to those of industrialized populations. Sample-wide, Garisakang cortisol concentrations are highest upon waking (mean = 4.86 nmol/L) and decrease throughout the day at a mean rate of only -0.18 nmol/L/h or -6.20%/h. Age and sex significantly predict evaluated cortisol parameters in ways not consistently reported among industrialized populations, suggesting that Garisakang diurnal cortisol rhythms are defined by distinct ontogenetic trajectories across the lifespan. These findings highlight cross-cultural diversity in HPA activity and have important implications for understanding basic mechanisms of the physiological stress response in contexts of chronic physical stressors such as limited nutrition, heavy burden of infectious disease, and high levels of physical activity.
- MeSH
- cirkadiánní rytmus fyziologie MeSH
- cvičení MeSH
- dítě MeSH
- dospělí MeSH
- fyziologický stres fyziologie MeSH
- hydrokortison analýza MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- předškolní dítě MeSH
- senioři MeSH
- sliny chemie MeSH
- systém hypofýza - nadledviny fyziologie MeSH
- systém hypotalamus-hypofýza fyziologie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Papua Nová Guinea MeSH
Brain acetylcholinesterase (AChE) variant AChERexpression increases with acute stress, and this persists for an extended period, although the timing, strain and laterality differences, have not been explored previously. Acute stress transiently increases acetylcholine release, which in turn may increase activity of cholinesterases. Also the AChE gene contains a glucocorticoid response element (GRE), and stress-inducible AChE transcription and activity changes are linked to increased glucocorticoid levels. Corticotropin-releasing hormone knockout (CRH-KO) mice have basal glucocorticoid levels similar to wild type (WT) mice, but much lower levels during stress. Hence we hypothesized that CRH is important for the cholinesterase stress responses, including butyrylcholinesterase (BChE). We used immobilization stress, acute (30 or 120 min) and repeated (120 min daily × 7) in 48 male mice (24 WT and 24 CRH-KO) and determined AChER, AChE and BChE mRNA expression and AChE and BChE activities in left and right brain areas (as cholinergic signaling shows laterality). Immobilization decreased BChE mRNA expression (right amygdala, to 0.5, 0.3 and 0.4, × control respectively) and AChERmRNA expression (to 0.5, 0.4 and 0.4, × control respectively). AChE mRNA expression increased (1.3, 1.4 and 1.8-fold, respectively) in the left striatum (Str). The AChE activity increased in left Str (after 30 min, 1.2-fold), decreased in right parietal cortex with repeated stress (to 0.5 × control). BChE activity decreased after 30 min in the right CA3 region (to 0.4 × control) but increased (3.8-fold) after 120 min in the left CA3 region. The pattern of changes in CRH-KO differed from that in WT mice.
- MeSH
- acetylcholinesterasa metabolismus MeSH
- butyrylcholinesterasa metabolismus MeSH
- funkční lateralita fyziologie MeSH
- fyzické omezení MeSH
- fyziologický stres fyziologie MeSH
- hormon uvolňující kortikotropin genetika metabolismus MeSH
- mozek metabolismus MeSH
- myši knockoutované MeSH
- myši MeSH
- psychický stres metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Stress as a modern civilization factor significantly affects our lives. While acute stress might have a positive effect on the organism, chronic stress is usually detrimental and might lead to serious health complications. It is known that stress induced by the physical environment (temperature-induced cold stress) can significantly impair the efficacy of cytotoxic chemotherapies and the anti-tumor immune response. On the other hand, epidemiological evidence has shown that patients taking drugs known as β-adrenergic antagonists ("β-blockers"), which are commonly prescribed to treat arrhythmia, hypertension, and anxiety, have significantly lower rates of several cancers. In this review, we summarize the current knowledge about catecholamines as important stress hormones in tumorigenesis and discuss the use of β-blockers as the potential therapeutic agents.
- MeSH
- adrenalin metabolismus MeSH
- karcinogeneze metabolismus MeSH
- katecholaminy metabolismus MeSH
- lidé MeSH
- nádory etiologie metabolismus MeSH
- noradrenalin metabolismus MeSH
- psychický stres komplikace metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Many modalities of cognition are affected in schizophrenia. The most common findings include dysfunctions of episodic and working memory and of executive functions. Although an inverse correlation between cortisol level and memory function has been proven, few studies have focused on the relationship between cortisol level and cognitive impairment in patients with schizophrenia. In an open, naturalistic, prospective study, consecutively hospitalized males diagnosed with first-episode schizophrenia, hypothalamic-pituitary-adrenal axis activity (afternoon cortisol levels, post-dexamethasone cortisol levels) was evaluated before and at the end of acute treatment. Psychopathology was assessed using the positive and negative syndrome scale (PANSS). Cognitive functions (memory, attention, psychomotor, verbal fluency, and executive functions) were tested after symptom alleviation using a neurocognitive test battery. In the total sample (n = 23), significant decreases in total PANSS score (including all subscales), afternoon cortisol levels, and post-dexamethasone cortisol levels occurred during the course of treatment. It was found that higher afternoon cortisol levels at the beginning of treatment were significantly related to impaired performance in memory functions. Afternoon cortisol levels were not significantly associated with other measured cognitive functions. No correlation was discovered between cognitive functions and post-dexamethasone cortisol levels. The determination of afternoon cortisol levels may serve to detect potential candidates for specific cognitive intervention immediately after the first psychotic breakthrough.
- MeSH
- dexamethason MeSH
- dospělí MeSH
- exekutivní funkce fyziologie MeSH
- hydrokortison krev MeSH
- kognice fyziologie MeSH
- kognitivní dysfunkce krev komplikace patofyziologie MeSH
- kognitivní poruchy komplikace patofyziologie psychologie MeSH
- krátkodobá paměť fyziologie MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- neuropsychologické testy MeSH
- pozornost fyziologie MeSH
- prospektivní studie MeSH
- schizofrenie (psychologie) * MeSH
- schizofrenie krev komplikace MeSH
- systém hypofýza - nadledviny patofyziologie MeSH
- systém hypotalamus-hypofýza patofyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
We hypothesized that muscarinic receptors (MRs) in the heart have a role in stress responses and thus investigated changes in MR signaling (gene expression, number of receptors, adenylyl cyclase (AC), phospholipase C (PLC), protein kinase A and C (PKA and PKC) and nitric oxide synthase [NOS]) in the left ventricle, together with telemetric measurement of heart rate (HR) in mice (wild type [WT] and M2 knockout [KO]) during and after one (1R) or seven sessions (7R) of restraint stress (seven mice per group). Stress decreased M2 MR mRNA and cell surface MR in the left ventricle in WT mice. In KO mice, 1R, but not 7R, decreased surface MR. Similarly, AC activity was decreased in WT mice after 1R and 7R, whereas in KO mice, there was no change. PLC activity was also decreased after 1R in WT and KO mice. This is in accord with the concept that cAMP is a key player in HR regulation. No change was found with stress in NOS activity. Amount of AC and PKA protein was not changed, but was altered for PKC isoenzymes (PKCα, β, γ, η and ϵ (increased) in KO mice, and PKCι (increased) in WT mice). KO mice were more susceptible to stress as shown by inability to compensate HR during 120 min following repeated stress. The results imply that not only M2 but also M3 are involved in stress signaling and in allostasis. We conclude that for a normal stress response, the expression of M2 MR to mediate vagal responses is essential.
- MeSH
- adenylátcyklasy metabolismus MeSH
- AMP cyklický metabolismus MeSH
- exprese genu MeSH
- fosfolipasy typu C metabolismus MeSH
- fyzické omezení MeSH
- myši knockoutované MeSH
- myši MeSH
- proteinkinasa C metabolismus MeSH
- proteinkinasy závislé na cyklickém AMP metabolismus MeSH
- psychický stres genetika patofyziologie MeSH
- receptor muskarinový M2 genetika MeSH
- receptory muskarinové genetika MeSH
- signální transdukce MeSH
- srdce MeSH
- srdeční frekvence genetika fyziologie MeSH
- srdeční komory metabolismus MeSH
- synthasa oxidu dusnatého metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
We tested the hypothesis that single and repeated immobilization stress affect densities of alpha(1)-adrenoceptor (alpha(1)-AR) and beta-AR subtypes, muscarinic receptors (MR), adenylyl cyclase activity (AC) and phospholipase C activity (PLC) in lungs of male and female wild type (WT) and corticotropin-releasing hormone gene (CRH-knockout (KO)) disrupted mice. We found sex differences in the basal levels of alpha(1)-AR subtypes (females had 2-3 times higher density of receptors than males) and MR (males had twice the density found in females). In marked contrast, beta-AR subtype densities did not differ between sexes. CRH gene disruption decreased all three studied receptors in intact mice (to 20-50% of WT) in both sexes (except beta(1)-AR in females). Stress induced sexually dimorphic responses, while all alpha(1)-AR subtypes decreased in females (to 30% of control approximately), only alpha(1A)-AR level diminished (about 50%) in males. beta(1)-AR decreased in males (to about 40%) but remained stable in females. beta(2)-AR diminished in females (to about 20-60%) and also in males (to about 30-60%). MR decreased in both sexes (approximately to 50%). AC activity diminished in males (to < 50%) while PLC activity was not changed. In CRH-KO mice, the stress response was severely diminished. Paradoxically, the receptor response to stress was less affected by CRH-KO in males than in females. AC activity did not change in CRH-KO mice. In conclusion, in mice the stress reaction is sexually dimorphic and an intact hypothalamo-pituitary-adrenocortical system is required for the normal reaction of pulmonary adrenergic and MR to stress.
- MeSH
- alfa-1-adrenergní receptory metabolismus MeSH
- beta-adrenergní receptory metabolismus MeSH
- fyzické omezení MeSH
- fyziologický stres fyziologie MeSH
- hormon uvolňující kortikotropin genetika metabolismus MeSH
- myši knockoutované MeSH
- myši MeSH
- plíce metabolismus MeSH
- pohlavní dimorfismus MeSH
- receptory muskarinové metabolismus MeSH
- sexuální faktory MeSH
- systém hypofýza - nadledviny metabolismus MeSH
- systém hypotalamus-hypofýza metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- finanční podpora výzkumu jako téma MeSH
- fyziologický stres patofyziologie MeSH
- krysa rodu rattus MeSH
- kůra nadledvin patofyziologie MeSH
- systém hypofýza - nadledviny patofyziologie MeSH
- systém hypotalamus-hypofýza patofyziologie MeSH
- těhotenství MeSH
- zpožděný efekt prenatální expozice MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- těhotenství MeSH
- zvířata MeSH
