Despite the recent progress in research and therapy, cardiovascular diseases are still the most common cause of death worldwide, thus new approaches are still needed. The aim of this review is to highlight the cardioprotective potential of urocortins and corticotropin-releasing hormone (CRH) and their signaling. It has been documented that urocortins and CRH reduce ischemic and reperfusion (I/R) injury, prevent reperfusion ventricular tachycardia and fibrillation, and improve cardiac contractility during reperfusion. Urocortin-induced increase in cardiac tolerance to I/R depends mainly on the activation of corticotropin-releasing hormone receptor-2 (CRHR2) and its downstream pathways including tyrosine kinase Src, protein kinase A and C (PKA, PKCε) and extracellular signal-regulated kinase (ERK1/2). It was discussed the possibility of the involvement of interleukin-6, Janus kinase-2 and signal transducer and activator of transcription 3 (STAT3) and microRNAs in the cardioprotective effect of urocortins. Additionally, phospholipase-A2 inhibition, mitochondrial permeability transition pore (MPT-pore) blockade and suppression of apoptosis are involved in urocortin-elicited cardioprotection. Chronic administration of urocortin-2 prevents the development of postinfarction cardiac remodeling. Urocortin possesses vasoprotective and vasodilator effect; the former is mediated by PKC activation and prevents an impairment of endothelium-dependent coronary vasodilation after I/R in the isolated heart, while the latter includes both cAMP and cGMP signaling and its downstream targets. As CRHR2 is expressed by both cardiomyocytes and vascular endothelial cells. Urocortins mediate both endothelium-dependent and -independent relaxation of coronary arteries.

• MeSH
• hormon uvolňující kortikotropin farmakologie   MeSH
• hormony farmakologie   MeSH
• kardiovaskulární fyziologické jevy účinky léků   MeSH
• kardiovaskulární nemoci farmakoterapie   MeSH
• kardiovaskulární systém účinky léků   MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• reperfuzní poškození farmakoterapie   MeSH
• urokortiny farmakologie   MeSH
• vazodilatace účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Mateřská deprese je jednou z nejčastějších prenatálních a postnatálních komplikací. Takové komplikace mohou vážně ohrozit neuropsychický vývoj nového jedince. Článek poskytuje přehled možných biologických, neurologických a psychologických faktorů, které mohou být zahrnuty mezi faktory rizikové. Perinatální deprese matky je prezentována a diskutována jako příklad interakce placentárních, epigenetických a raných rodičovských faktorů, které zvyšují riziko narušení vývoje plodu, novorozence, kojence a dítěte v dalších věkových obdobích. Dostupné důkazy poukazují na důležitost vlivů, které působí na jedince již v děloze matky, stejně jako na význam časné citové vazby a mateřské péče. Je zřejmé, že modely rané etiologie duševních poruch, jakou je i perinatální deprese, jsou složité s řadou potenciálních faktorů od genetických a epigenetických až po faktory prostředí, jež ovlivňují neurologický, emoční a psychosociální vývoj.

Maternal depression is one of the most common prenatal and postnatal complications. Such complications may seriously compromised the neuropsychological development of the new being. This paper provides an overview of potential biological, neurological and psychological factors that might be involved into the risk factors. Perinatal maternal depression is presented and reviewed as an example of the interaction of placental, epigenetic and early parenting factors elevating risk of poor fetus, neonatal, infant and child development. Available evidence points to the importance of in-utero influences as well as the importance of early attachment and parenting. It is pointed out that models of the early aetiology of mental disorders, such as perinatal depression, are complex with a range of potential factors from genetic and epigenetic to environmental influencing neurological, emotional and psychosocial development.

• Klíčová slova
• citlivost,
• MeSH
• centrální nervový systém fyziologie   růst a vývoj   MeSH
• deprese * epidemiologie   etiologie   genetika   psychologie   MeSH
• epigeneze genetická fyziologie   MeSH
• hormon uvolňující kortikotropin fyziologie   MeSH
• interakce genů a prostředí MeSH
• lidé MeSH
• novorozenec MeSH
• peripartální období fyziologie   genetika   psychologie   MeSH
• placenta fyziologie   MeSH
• připoutání k objektu MeSH
• rodičovství psychologie   MeSH
• sociální interakce MeSH
• těhotenství MeSH
• vývoj dítěte * MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• přehledy MeSH

• MeSH
• galanin fyziologie   MeSH
• gastrointestinální hormony fyziologie   MeSH
• hormon uvolňující gonadotropiny analýza   metabolismus   MeSH
• hormon uvolňující kortikotropin analýza   metabolismus   MeSH
• hypothalamus fyziologie   metabolismus   MeSH
• inzulin fyziologie   metabolismus   MeSH
• leptin analýza   metabolismus   MeSH
• lidé MeSH
• mentální anorexie metabolismus   patofyziologie   MeSH
• neuropeptid Y fyziologie   MeSH
• neurosekreční systémy fyziologie   patofyziologie   MeSH
• obezita etiologie   metabolismus   patofyziologie   MeSH
• orexiny fyziologie   metabolismus   MeSH
• poruchy příjmu potravy etiologie   metabolismus   patofyziologie   MeSH
• regulace chuti k jídlu fyziologie   MeSH
• systém hypotalamus-hypofýza patofyziologie   MeSH
• tuková tkáň chemie   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

The activation of the HPA axis is the endocrine measure of stress responsiveness that is initiated by corticotropin-releasing hormone (CRH). CRH exerts its effects via CRHR1 and CRH-R2 receptors coupled to the cAMP signaling system and this process involves transcription factor cAMP-responsive element-binding protein (CREB).This study investigated the role of CRH and the possible involvement of CREB in gene regulation of CRH receptor, under basal conditions and after stress application in the pituitary. We used wild type (wt +/+) controls and CRH knock-out (CRH-KO -/-) male mice. Using CRH-deficient mice, we were able to investigate the consequences of the lack of the CRH on the expression of CRH receptors and transcriptional regulation mediated by CREB. We estimated the effect of acute (IMO 1×) and repeated (IMO 7×) restraint stressors lasting 30 and 120 min on the expression of mRNA CREB, CRH-R1, and CRH-R2 by qPCR. We found very significant difference in the expression of these peptides under the effect of single and repeated stress in control and CRH-KO mice. Our results indicate that both CRH receptors and CREB might be involved in the regulation of stress response in the pituitary of mice. We propose that regulation of the stress response may be better understood if more were known about the mechanisms of CRH receptor signal transduction and involvement of CREB system.

• MeSH
• akutní nemoc MeSH
• hormon uvolňující kortikotropin biosyntéza   nedostatek   MeSH
• hypofýza metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• protein vázající element responzivní pro cyklický AMP biosyntéza   MeSH
• psychický stres metabolismus   psychologie   MeSH
• receptory hormonu uvolňujícího kortikotropin biosyntéza   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Corticotropin-releasing hormone (CRH) is involved in modification of synaptic transmission and affects spatial discrimination learning, i.e., affects the formation of memory in long-term aspect. Therefore, we have focused on CRH effect on short-term memory. We have used stress task avoidance (maze containing three zones: entrance, aversive, and neutral) and compared the behavior and short-term memory in wild-type mice and mice lacking CRH (CRH KO) experiencing one 120-min session of restraint stress. As control, non-stressed animals were used. As expected, the animals that experienced the stress situation tend to spend less time in the zone in which the restraint chamber was present. The animals spent more time in the neutral zone. There were significant differences in number of freezing bouts in the aversive and entrance zones in CRH KO animals. CRH KO control animals entered the neutral zone much more faster than WT control and spent more time immobile in the neutral zone than WT control. These data give evidence that lacking of CRH itself improves the ability of mice to escape away from potentially dangerous area (i.e., those in which the scent of stressed animal is present).

• MeSH
• hormon uvolňující kortikotropin nedostatek   MeSH
• krátkodobá paměť fyziologie   MeSH
• myši inbrední C57BL MeSH
• myši kmene 129 MeSH
• myši knockoutované MeSH
• myši MeSH
• psychický stres metabolismus   psychologie   MeSH
• učení vyhýbat se fyziologie   MeSH
• úniková reakce fyziologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články 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

The present study investigated the effects of nesfatin-1 on gastric distension (GD)-responsive neurons via an interaction with corticotropin-releasing factor (CRF) receptor signaling in the ventromedial hypothalamic nucleus (VMH), and the potential regulation of these effects by hippocampal projections to VMH. Extracellular single-unit discharges were recorded in VHM following administration of nesfatin-1. The projection of nerve fibers and expression of nesfatin-1 were assessed by retrograde tracing and fluoro-immunohistochemical staining, respectively. Results showed that there were GD-responsive neurons in VMH; Nesfatin-1 administration and electrical stimulation of hippocampal CA1 sub-region altered the firing rate of these neurons. These changes could be partially blocked by pretreatment with the non-selective CRF antagonist astressin-B or an antibody to NUCB2/nesfatin-1. Electrolytic lesion of CA1 hippocampus reduced the effects of nesfatin-1 on VMH GD-responsive neuronal activity. These studies suggest that nesfatin-1 plays an important role in GD-responsive neuronal activity through interactions with CRF signaling pathways in VMH. The hippocampus may participate in the modulation of nesfatin-1-mediated effects in VMH.

• MeSH
• akční potenciály fyziologie   MeSH
• DNA vazebné proteiny metabolismus   MeSH
• gastrointestinální motilita fyziologie   MeSH
• hormon uvolňující kortikotropin metabolismus   MeSH
• krysa rodu rattus MeSH
• neurony fyziologie   MeSH
• nucleus ventromedialis hypothalami fyziologie   MeSH
• potkani Wistar MeSH
• proteiny nervové tkáně metabolismus   MeSH
• proteiny vázající vápník metabolismus   MeSH
• žaludek fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články 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

Pituitary corticotrophs fire action potentials spontaneously and in response to stimulation with corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP), and such electrical activity is critical for calcium signaling and calcium-dependent adrenocorticotropic hormone secretion. These cells typically fire tall, sharp action potentials when spontaneously active, but a variety of other spontaneous patterns have also been reported, including various modes of bursting. There is variability in reports of the fraction of corticotrophs that are electrically active, as well as their patterns of activity, and the sources of this variation are not well understood. The ionic mechanisms responsible for CRH- and AVP-triggered electrical activity in corticotrophs are also poorly characterized. We use electrophysiological measurements and mathematical modeling to investigate possible sources of variability in patterns of spontaneous and agonist-induced corticotroph electrical activity. In the model, variation in as few as two parameters can give rise to many of the types of patterns observed in electrophysiological recordings of corticotrophs. We compare the known mechanisms for CRH, AVP, and glucocorticoid actions and find that different ionic mechanisms can contribute in different but complementary ways to generate the complex time courses of CRH and AVP responses. In summary, our modeling suggests that corticotrophs have several mechanisms at their disposal to achieve their primary function of pacemaking depolarization and increased electrical activity in response to CRH and AVP.NEW & NOTEWORTHYWe and others recently demonstrated that the electrical activity and calcium dynamics of corticotrophs are strikingly diverse, both spontaneously and in response to the agonists CRH and AVP. Here we demonstrate this diversity with electrophysiological measurements and use mathematical modeling to investigate its possible sources. We compare the known mechanisms of agonist-induced activity in the model, showing how the context of ionic conductances dictates the effects of agonists even when their target is fixed.

• MeSH
• akční potenciály * MeSH
• arginin vasopresin metabolismus   MeSH
• hormon uvolňující kortikotropin metabolismus   MeSH
• iontové kanály metabolismus   MeSH
• kortikotropní buňky metabolismus   fyziologie   MeSH
• kultivované buňky MeSH
• modely neurologické * MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Transgenic mice expressing the tdimer2(12) form of Discosoma red fluorescent protein under control of the proopiomelanocortin gene's regulatory elements are a useful model for studying corticotrophs. Using these mice, we studied the ion channels and mechanisms controlling corticotroph excitability. Corticotrophs were either quiescent or electrically active, with a 22-mV difference in the resting membrane potential (RMP) between the 2 groups. In quiescent cells, CRH depolarized the membrane, leading to initial single spiking and sustained bursting; in active cells, CRH further facilitated or inhibited electrical activity and calcium spiking, depending on the initial activity pattern and CRH concentration. The stimulatory but not inhibitory action of CRH on electrical activity was mimicked by cAMP independently of the presence or absence of arachidonic acid. Removal of bath sodium silenced spiking and hyperpolarized the majority of cells; in contrast, the removal of bath calcium did not affect RMP but reduced CRH-induced depolarization, which abolished bursting electrical activity and decreased the spiking frequency but not the amplitude of single spikes. Corticotrophs with inhibited voltage-gated sodium channels fired calcium-dependent action potentials, whereas cells with inhibited L-type calcium channels fired sodium-dependent spikes; blockade of both channels abolished spiking without affecting the RMP. These results indicate that the background voltage-insensitive sodium conductance influences RMP, the CRH-depolarization current is driven by a cationic conductance, and the interplay between voltage-gated sodium and calcium channels plays a critical role in determining the status and pattern of electrical activity and calcium signaling.

• MeSH
• akční potenciály účinky léků   MeSH
• AMP cyklický metabolismus   MeSH
• dibutyryl cyklický AMP farmakologie   MeSH
• hormon uvolňující kortikotropin farmakologie   MeSH
• iontové kanály metabolismus   MeSH
• kolforsin farmakologie   MeSH
• kortikotropní buňky účinky léků   metabolismus   fyziologie   MeSH
• kultivované buňky MeSH
• kyselina arachidonová farmakologie   MeSH
• membránové potenciály účinky léků   MeSH
• metoda terčíkového zámku MeSH
• myši inbrední C57BL MeSH
• myši transgenní MeSH
• sodík metabolismus   MeSH
• vápník metabolismus   MeSH
• vápníková signalizace účinky léků   MeSH
• vápníkové kanály - typ L metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Intramural MeSH