OBJECTIVES: Oxytocin (OT) is a neuropeptide acting both as a peripheral hormone and in the brain as neurotransmitter and neuromodulator. In addition to its well-known effects on milk-ejection and uterine contraction, OT was shown to exert neuroendocrine regulation of heart functions. The aim of this study was to investigate the expression of mRNA of OT receptors (OTR) in rat hearts by real-time quantitative PCR (qPCR). The study was performed in Sprague-Dawley (SD) and Lewis (LE) rat strains, the latter having lower activity of HPA axis. METHODS: We used adult male SD and LE rats. OTR mRNA expression was detected in all heart chambers by comparing their threshold cycle values (CT) to CT of reference gene β-actin. The relative expression ratios were calculated using the 2-ΔΔCT method. The specificity of reaction of primary antibody with OTRs was tested by Western Blot and localization of OTR in the heart compartments was performed by immunofluorescence with commercial OTR specific antibodies. RESULTS: We found expression of OTR mRNA in all heart compartments. The expression of OTR mRNA in both atria (LA, RA) was much higher than in the ventricles (RV, LV). By using two-way ANOVA we found no statistical differences between corresponding compartments of SD and LE rats. Immunohistochemical studies showed that OTR staining is not related to neuronal tissue and findings from left atrium indicate that prevalent localization of OTR is on cell membranes of cardiomyocytes. CONCLUSIONS: The finding of expression of OTR mRNA by real-time qPCR and proof of OTR staining by immunohistochemistry in all heart compartments indicate that OT and its receptors may have function as a cardiovascular hormone. The differences in the HPA axis activity, as is exemplified in Sprague-Dawley and Lewis rat strain, do not project in the expression of OTR mRNA under basal condition. The effect of activity of HPA on OTR expression should be studied under stimulated conditions as it was performed in the behavioral studies.

• MeSH
• krysa rodu rattus MeSH
• messenger RNA metabolismus   MeSH
• myokard cytologie   metabolismus   MeSH
• oxytocin metabolismus   MeSH
• potkani inbrední LEW MeSH
• potkani Sprague-Dawley MeSH
• receptory oxytocinu genetika   metabolismus   MeSH
• systém hypofýza - nadledviny fyziologie   MeSH
• systém hypotalamus-hypofýza fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

In recent years, several studies have explored the involvement of the deregulation of the hypothalamus-pituitary-adrenal (HPA) axis in the pathophysiology of stress-related disorders. HPA hyper-activation as a consequence of acute/chronic stress has been found to play a major role in the neurobiological changes that are responsible for the onset of such states. Currently available medications for depression, one of the most relevant stress-related disorders, present several limitations, including a time lag for treatment response and low rates of efficacy. N-Arachidonoylserotonin (AA-5-HT), a dual blocker at fatty acid amide hydrolase (FAAH, the enzyme responsible for the inactivation of the endocannabinoid anandamide) and transient receptor potential vanilloid type-1 channel (TRPV1), produces anxiolytic-like effects in mice. The present study was designed to assess the capability of AA-5-HT to reverse the behavioral despair following exposure to stress in rats and the role of the HPA-axis. Behavioral tasks were performed, and corticosterone and endocannabinoid (anandamide and 2-arachidonoylglycerol) levels were measured in selected brain areas critically involved in the pathophysiology of stress-related disorders (medial PFC and hippocampus) under basal and stress conditions, and in response to treatment with AA-5-HT. Our data show that AA-5-HT reverses the rat behavioral despair in the forced swim test under stress conditions, and this effect is associated with the normalization of the HPA-axis deregulation that follows stress application and only in part with elevation of anandamide levels. Blockade of FAAH and TRPV1 may thus represent a novel target to design novel therapeutic strategies for the treatment of stress-related disorders.

• MeSH
• amidohydrolasy antagonisté a inhibitory   genetika   metabolismus   MeSH
• chování zvířat účinky léků   MeSH
• endokanabinoidy metabolismus   MeSH
• fyzické omezení MeSH
• glyceridy metabolismus   MeSH
• kationtové kanály TRPV antagonisté a inhibitory   genetika   metabolismus   MeSH
• kortikosteron krev   MeSH
• krysa rodu rattus MeSH
• kyseliny arachidonové metabolismus   farmakologie   terapeutické užití   MeSH
• mozek účinky léků   metabolismus   MeSH
• mozkový neurotrofický faktor genetika   metabolismus   MeSH
• plavání MeSH
• polynenasycené alkamidy metabolismus   MeSH
• potkani Wistar MeSH
• psychický stres krev   farmakoterapie   metabolismus   MeSH
• serotonin analogy a deriváty   farmakologie   terapeutické užití   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

Several deleterious effects may occur when intense and exhaustive exercise (IE) is not well-planned. This study aimed to investigate the effects of a short duration IE on body chemical composition and hypothalamic-pituitary-adrenal (HPA) axis. C57Bl/6 mice were distributed into four groups (10 mice per group): control (C-4D and C-10D), 4 days (E-4D), and 10 days of IE (E-10D). IE program consisted of a daily running session at 85 % of maximum speed until the animal reached exhaustion. Body weight as well as total body water, fat and protein content were determined from animal carcasses. HPA activation was assessed by plasma corticosterone levels measured by radioimmunoassay and the weight of both the adrenal glands and thymus were measured. Plasma corticosterone levels increased by 64 % in both the E-4D and E-10D groups. The weight of the adrenal glands augmented by 74 % and 45 %, at 4 and 10 days of IE, respectively, whereas thymus weight diminished by 15 % only in the E-10D group. The total carcass fat content decreased by 20 % only at 4 days IE, whereas protein content decreased by 20 % in both E-4D and E-10D groups. A relationship between corticosterone plasma levels and loss of body protein content in both E-4D and E-10D groups was observed (R(2)=0.999). We concluded that IE may be related to HPA axis activation associated with remodeling of body chemical composition in C57BL/6 mice.

• MeSH
• běh MeSH
• biologické markery krev   MeSH
• časové faktory MeSH
• fyziologický stres * MeSH
• kortikosteron krev   MeSH
• kosterní svaly anatomie a histologie   metabolismus   MeSH
• myši inbrední C57BL MeSH
• nadledviny anatomie a histologie   metabolismus   MeSH
• proteiny metabolismus   MeSH
• proteolýza MeSH
• složení těla * MeSH
• svalová únava * MeSH
• systém hypofýza - nadledviny anatomie a histologie   metabolismus   MeSH
• systém hypotalamus-hypofýza metabolismus   MeSH
• tělesná námaha * MeSH
• thymus anatomie a histologie   MeSH
• velikost orgánu MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The commensal microbiota affects brain functioning, emotional behavior and ACTH and corticosterone responses to acute stress. However, little is known about the role of the microbiota in shaping the chronic stress response in the peripheral components of the hypothalamus-pituitary-adrenocortical (HPA) axis and in the colon. Here, we studied the effects of the chronic stress-microbiota interaction on HPA axis activity and on the expression of colonic corticotropin-releasing hormone (CRH) system, cytokines and 11β-hydroxysteroid dehydrogenase type 1 (11HSD1), an enzyme that determines locally produced glucocorticoids. Using specific pathogen-free (SPF) and germ-free (GF) BALB/c mice, we showed that the microbiota modulates emotional behavior in social conflicts and the response of the HPA axis, colon and mesenteric lymph nodes (MLN) to chronic psychosocial stress. In the pituitary gland, microbiota attenuated the expression of Fkbp5, a gene regulating glucocorticoid receptor sensitivity, while in the adrenal gland, it attenuated the expression of genes encoding steroidogenesis (MC2R, StaR, Cyp11a1) and catecholamine synthesis (TH, PNMT). The pituitary expression of CRH receptor type 1 (CRHR1) and of proopiomelanocortin was not influenced by microbiota. In the colon, the microbiota attenuated the expression of 11HSD1, CRH, urocortin UCN2 and its receptor, CRHR2, but potentiated the expression of cytokines TNFα, IFNγ, IL-4, IL-5, IL-6, IL-10, IL-13 and IL-17, with the exception of IL-1β. Compared to GF mice, chronic stress upregulated in SPF animals the expression of pituitary Fkbp5 and colonic CRH and UCN2 and downregulated the expression of colonic cytokines. Differences in the stress responses of both GF and SPF animals were also observed when immunophenotype of MLN cells and their secretion of cytokines were analyzed. The data suggest that the presence of microbiota/intestinal commensals plays an important role in shaping the response of peripheral tissues to stress and indicates possible pathways by which the environment can interact with glucocorticoid signaling.

• MeSH
• 11-beta-hydroxysteroiddehydrogenasa typ 1 metabolismus   MeSH
• adrenokortikotropní hormon metabolismus   MeSH
• chování zvířat fyziologie   MeSH
• cytokiny metabolismus   MeSH
• exprese genu fyziologie   MeSH
• glukokortikoidy genetika   fyziologie   MeSH
• hormon uvolňující kortikotropin metabolismus   MeSH
• hypofýza MeSH
• kortikosteron metabolismus   MeSH
• mikrobiota fyziologie   MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• nadledviny MeSH
• psychický stres genetika   metabolismus   MeSH
• psychologie MeSH
• receptory glukokortikoidů metabolismus   MeSH
• regulace genové exprese fyziologie   MeSH
• sociální chování MeSH
• systém hypofýza - nadledviny mikrobiologie   MeSH
• systém hypotalamus-hypofýza mikrobiologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVES: Cardiovascular system is regulated by a diverse array of hormones, neurotransmitters and neuropeptides. Oxytocin and its receptors (OTR) were also shown to regulate cardiovascular functions and this hormone was even called cardiovascular hormone. In recent publication, we demonstrated the expression of mRNA of OTR by real-time quantitative PCR (RT qPCR) in all rat heart compartments. The aim of this study was to investigate the effects of acute restraint stress on OTR mRNA expression in two rat strains with different activity of HPA axis. METHODS: Adult male Sprague-Dawley and Lewis rats, the latter strain reported to have lower HPA activity, were used in RT qPCR studies and Wistar rats in immunofluorescent ones. Both acute restraint (IS) and this stress combined with the immersion of rats in water (ICS) lasted 60 min. Gene expression of OTR mRNA was estimated in all heart compartments after 1 or 3 hours after stress termination (IS1, IS3, ICS1, ICS3). The relative expression was calculated using 2(-ΔΔC)T method. In immunofluorescent studies we used commercial specific OTR antibodies. RESULTS: In RT qPCR studies we found higher expression of OTR mRNA in atria than in ventricles and no statistical differences between Sprague-Dawley and Lewis rats under basal conditions. Relative expression of OTR mRNA after 60 min lasting stress exposure differed in dependence on the stress type and partly on the time interval after the stress termination. When compared to controls, in rat left atria both stressors caused inhibition of OTR mRNA expression in both rat strains. In rat ventricles, which have very low OTR mRNA expression, there was a significant difference in the effect of two stressors. In most groups ICS displayed the increase of OTR mRNA expression if compared to IS groups. Immunofluorescent studies revealed changes induced by acute restraint stress in all heart compartments. The immunofluorescent studies suggested that acute stress induces higher colocalization of OTR with the nuclei than it was observed in the controls. CONCLUSIONS: The expression of OTR mRNA in all heart compartments of controls as well as after stress exposure in Sprague-Dawley and Lewis rats support the notion that OTR plays a regulatory role in the cardiovascular system and is also involved in the regulations in the heart after stress. The immunofluorescent observation that OTRs coexpress in areas of cell nuclei in certain heart compartments and after acute stress, compared to controls, requires further studies.

• MeSH
• druhová specificita MeSH
• exprese genu fyziologie   MeSH
• fyzické omezení metody   MeSH
• fyziologický stres fyziologie   MeSH
• krysa rodu rattus MeSH
• myokard cytologie   metabolismus   MeSH
• potkani inbrední LEW MeSH
• potkani Sprague-Dawley MeSH
• potkani Wistar MeSH
• receptory oxytocinu biosyntéza   metabolismus   MeSH
• systém hypofýza - nadledviny fyziologie   MeSH
• systém hypotalamus-hypofýza fyziologie   MeSH
• transport proteinů MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Objective: Proinflammatory cytokines IL-1ß, and IL-6 are synthesized in the brain, where they exert local regulatory functions. Our aim was to find out whether, along with the activation of hypothalamo-pituitary-adrenocortical (HPA) axis and prolactin (PRL), the acute systemic enhancement of IL-1ß affects its own production in the hypothalamus as well as that of IL-6. Method: Forty five minutes after a single i.p. administration of recombinant rat IL-1ß (5 μg/kg) to male Long Evans rats we estimated the expression of IL-1ß and IL-6 mRNA in the hypothalamus by real time PCR, ACTH, corticosterone (CORT), and PRL by RIA Results: IL-1ß administration stimulated the expression of IL-1ß mRNA in the hypothalamus by 99 %, but not that of IL-6. It also significantly activated plasma levels of ACTH, PRL, CORT, and CORT production in adrenal gland. Conclusion: These results indicate that acute peripheral enhancement of IL-1ß may induce neuroendocrine changes also via the immediate activation of its own expression in the hypothalamus, but not that of IL-6 expression in the hypothalamus was found.

• MeSH
• adrenokortikotropní hormon krev   MeSH
• hypothalamus * metabolismus   účinky léků   MeSH
• interleukin-1beta farmakologie   metabolismus   MeSH
• interleukin-6 metabolismus   MeSH
• messenger RNA metabolismus   MeSH
• potkani Long-Evans MeSH
• prolaktin * krev   metabolismus   MeSH
• systém hypofýza - nadledviny metabolismus   účinky léků   MeSH
• systém hypotalamus-hypofýza účinky léků   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• 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

Sexual activity and/or reproduction are associated with a doubling of life expectancy in the long-lived rodent genus Fukomys. To investigate the molecular mechanisms underlying this phenomenon, we analyzed 636 RNA-seq samples across 15 tissues. This analysis suggests that changes in the regulation of the hypothalamic-pituitary-adrenal stress axis play a key role regarding the extended life expectancy of reproductive vs. non-reproductive mole-rats. This is substantiated by a corpus of independent evidence. In accordance with previous studies, the up-regulation of the proteasome and so-called 'anti-aging molecules', for example, dehydroepiandrosterone, is linked with enhanced lifespan. On the other hand, several of our results are not consistent with knowledge about aging of short-lived model organisms. For example, we found the up-regulation of the insulin-like growth factor 1/growth hormone axis and several other anabolic processes to be compatible with a considerable lifespan prolongation. These contradictions question the extent to which findings from short-lived species can be transferred to longer-lived ones.

• MeSH
• dehydroepiandrosteron farmakologie   MeSH
• dlouhověkost genetika   MeSH
• exprese genu MeSH
• insulinu podobný růstový faktor I metabolismus   MeSH
• mikroftalmičtí podzemní hlodavci genetika   metabolismus   MeSH
• psychický stres metabolismus   MeSH
• rozmnožování * MeSH
• sexuální chování zvířat MeSH
• systém hypofýza - nadledviny metabolismus   MeSH
• systém hypotalamus-hypofýza metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• krysa rodu rattus MeSH
• nucleus paraventricularis hypothalami MeSH
• systém hypotalamus-hypofýza MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH

• Publikační typ
• abstrakt z konference MeSH