Prolactin-releasing peptide (PrRP) has been proposed to mediate the central satiating effects of cholecystokinin (CCK) through the vagal CCK1 receptor. PrRP acts as an endogenous ligand of G protein-coupled receptor 10 (GPR10), which is expressed at the highest levels in brain areas related to food intake regulation, e.g., the paraventricular hypothalamic nucleus (PVN) and nucleus of the solitary tract (NTS). The NTS and PVN are also significantly activated after peripheral CCK administration. The aim of this study was to determine whether the endogenous PrRP neuronal system in the brain is involved in the central anorexigenic effect of the peripherally administered CCK agonist JMV236 or the CCK1 antagonist devazepide and whether the CCK system is involved in the central anorexigenic effect of the peripherally applied lipidized PrRP analog palm-PrRP31 in fasted lean mice. The effect of devazepide and JMV236 on the anorexigenic effects of palm-PrRP31 as well as devazepide combined with JMV236 and palm-PrRP31 on food intake and Fos cell activation in the PVN and caudal NTS was examined. Our results suggest that the anorexigenic effect of JMV236 is accompanied by activation of PrRP neurons of the NTS in a CCK1 receptor-dependent manner. Moreover, while the anorexigenic effect of palm-PrRP31 was not affected by JMV236, it was partially attenuated by devazepide in fasted mice. The present findings indicate that the exogenously influenced CCK system may be involved in the central anorexigenic effect of peripherally applied palm-PrRP31, which possibly indicates some interaction between the CCK and PrRP neuronal systems.
- MeSH
- anorektika aplikace a dávkování MeSH
- antagonisté hormonů aplikace a dávkování MeSH
- chemokiny CC účinky léků metabolismus MeSH
- cholecystokinin metabolismus MeSH
- devazepid aplikace a dávkování MeSH
- hormon uvolňující prolaktin aplikace a dávkování analogy a deriváty MeSH
- injekce intraperitoneální MeSH
- injekce subkutánní MeSH
- myši inbrední C57BL MeSH
- nucleus paraventricularis hypothalami účinky léků metabolismus MeSH
- nucleus solitarius účinky léků metabolismus MeSH
- omezení příjmu potravy MeSH
- peptidové fragmenty aplikace a dávkování MeSH
- přijímání potravy účinky léků MeSH
- protoonkogenní proteiny c-fos metabolismus MeSH
- signální transdukce MeSH
- sinkalid aplikace a dávkování analogy a deriváty MeSH
- stravovací zvyklosti účinky léků MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The aim of the present work was to study the influence of variable stress on the expression of 11β-hydroxysteroid dehydrogenase type 1 (11HSD1) and the neuropeptides corticotropin-releasing hormone (CRH), urocortins 2 and 3(UCN2, UCN3), arginine vasopressin (AVP), oxytocin (OXT) and adenylate cyclase-activating polypeptide (PACAP) in two inbred rat strains: stress hypo-responsive Lewis (LEW) and hyper-responsive Fisher 344 (F344) rats. We found site-specific and strain-dependent differences in the basal and stress-stimulated expression of 11HSD1, CRH, UCN2, UCN3 and PACAP. In LEW rats, stress upregulated 11HSD1 in the prefrontal cortex and lateral amygdala, whereas in F344 rats 11HSD1 was upregulated in the central amygdala and hippocampal CA2 and ventral but not dorsal CA1 region; no effect was observed in the paraventricular nucleus, pituitary gland and adrenal cortex of both strains. The expression of glucocorticoid receptors did not parallel the upregulation of 11HSD1. Stress also stimulated the expression of paraventricular OXT, CRH, UCN3 and PACAP in both strains but amygdalar CRH only in LEW and UCN2/UCN3 in F344 rats, respectively. The upregulation of PACAP and CRH was paralleled only by increased expression of PACAP receptor PAC1 but not CRH receptor type 1. These observations provide evidence that inbred F344 and LEW rats exhibit not only the well-known phenotypic differences in the activity of the HPA axis but also strain- and stress-dependent differences in the expression of genes encoding 11HSD1 and neuropeptides associated with the HPA axis activity. Moreover, the differences in 11HSD1 expression suggest different local concentration of corticosterone and access to GR in canonical and noncanonical structures of the HPA axis.
- MeSH
- 11-beta-hydroxysteroiddehydrogenasa typ 1 genetika metabolismus MeSH
- amygdala metabolismus MeSH
- arginin vasopresin genetika metabolismus MeSH
- hipokampus metabolismus MeSH
- hormon uvolňující kortikotropin genetika metabolismus MeSH
- hypofýza metabolismus MeSH
- hypofyzární adenylátcyklázu aktivující peptid genetika metabolismus MeSH
- krysa rodu rattus MeSH
- kůra nadledvin metabolismus MeSH
- messenger RNA metabolismus MeSH
- mozek metabolismus MeSH
- nucleus paraventricularis hypothalami metabolismus MeSH
- oxytocin genetika metabolismus MeSH
- potkani inbrední F344 MeSH
- potkani inbrední LEW MeSH
- prefrontální mozková kůra metabolismus MeSH
- psychický stres genetika metabolismus MeSH
- receptory glukokortikoidů genetika metabolismus MeSH
- stanovení celkové genové exprese MeSH
- systém hypofýza - nadledviny metabolismus MeSH
- systém hypotalamus-hypofýza metabolismus MeSH
- urokortiny genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
Generation of reactive oxygen species significantly contributes to the pathogenesis of acute renal failure (ARF) induced by myoglobin release. Ginsenosides (GS), the principal active ingredients of ginseng, is considered as an extremely good antioxidative composition of Chinese traditional and herbal drugs. The purpose of the present study was to investigate the protective effect of ginsenoside in rats with ARF on the changes of cholinergic nervous system in the kidney as well as on the involvement of mitogen-activated protein kinases (MAPK) in the hypothalamic paraventricular nuclei (PVN). In our assay, glycerol-induced acute renal failure in rats was employed to study the protective effects of ginsenoside. Our results indicated that the treatment of ARF rats with ginsenosides for 48 h significantly reduced lipid peroxidation, restored the superoxide dismutase (SOD) level. Meanwhile, the obvious increase of choline acetyltransferase-immunoreactivity (ChAT-IR) in the proximal convoluted tubular cells (PCT) was observed by immunohistochemistry in ARF+GS group. The same effect was also observed in the changes of p-ERK1/2-IR in the hypothalamic paraventricular nuclei. Our results suggest that ginsenoside administered orally may have a strong renal protective effect against glycerol-induced ARF, reduce the renal oxidative stress, and ginsenoside can also activate the cholinergic system in PCT, simultaneously MAPK signal pathway in the PVN was also activated.
- MeSH
- akutní poškození ledvin chemicky indukované enzymologie patologie prevence a kontrola MeSH
- antioxidancia aplikace a dávkování farmakologie MeSH
- aplikace orální MeSH
- časové faktory MeSH
- cholin-O-acetyltransferasa metabolismus MeSH
- cytoprotekce MeSH
- fosforylace MeSH
- ginsenosidy aplikace a dávkování farmakologie MeSH
- glycerol MeSH
- malondialdehyd metabolismus MeSH
- mitogenem aktivovaná proteinkinasa 1 metabolismus MeSH
- mitogenem aktivovaná proteinkinasa 3 metabolismus MeSH
- modely nemocí na zvířatech MeSH
- nucleus paraventricularis hypothalami účinky léků enzymologie MeSH
- oxidační stres účinky léků MeSH
- peroxidace lipidů účinky léků MeSH
- potkani Sprague-Dawley MeSH
- proximální tubuly ledvin účinky léků enzymologie patologie MeSH
- signální transdukce účinky léků MeSH
- superoxiddismutasa metabolismus MeSH
- upregulace MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The hypothalamic supraoptic and paraventricular nuclei consist of oxytocin and arginine vasopressin synthesizing neurons that send projections to the neurohypophysis. A growing body of evidence in adult animals and young animals at near term confirmed the structure and function in the vasopressinergic and oxytocinergic network. However, whether those distinctive neural networks are formed before near term is largely unknown. This study determined the special patterns in location and distribution of oxytocin- and vasopressin-neurons in the paraventricular and supraoptic nuclei from preterm to term in the ovine fetuses. The results showed that oxytocin- and vasopressin-neurons were present in both nuclei at the three gestational time periods (preterm, near term, and term). In the paraventricular nuclei, vasopressin-cells concentrated mainly in the core of the middle magnocellular paraventricular nuclei, and oxytocin-cells were scattered surrounding the core. In the supraoptic nuclei, vasopressin-cells mostly located in the ventral part, and oxytocin-cells in the dorsal part. The data demonstrated that the special distributed patterns of vasopressin- and oxytocin-neuron network have formed in those two nuclei at least from preterm. Intracerebroventricular injection of angiotensin II significantly increased fetal plasma oxytocin and vasopressin levels at preterm, which was associated with an increase of oxytocin- and vasopressin-neuron activity marked with c-fos expression. The data provided new evidence for the structural and functional development of the oxytocin- and vasopressin-network before birth.
- MeSH
- angiotensin II aplikace a dávkování MeSH
- arginin vasopresin krev metabolismus MeSH
- časové faktory MeSH
- gestační stáří MeSH
- injekce intraventrikulární MeSH
- nervová síť embryologie metabolismus MeSH
- neurony metabolismus účinky léků MeSH
- nucleus paraventricularis hypothalami embryologie metabolismus účinky léků MeSH
- nucleus supraopticus embryologie metabolismus účinky léků MeSH
- ovce MeSH
- oxytocin krev metabolismus MeSH
- protoonkogenní proteiny c-fos metabolismus MeSH
- těhotenství MeSH
- zvířata MeSH
- Check Tag
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVE: Obesity represents a low-grade inflammatory disease and appears a risk factor for insulin resistance, but little is known on whether this may contribute to the development of autoimmune inflammatory diseases. The aim of this work was to study the early-life diet-induced obesity in Lewis rats which are known to be highly susceptible to autoimmunity. METHODS: Obesity was induced by reduced litter size (4 pups per litter) followed by high-fat diet (SHF rats). Control rats (8 pups per litter) were fed with standard diet (CN rats). Oral glucose tolerance test (3 g glucose per kg b.w.) was performed by intra-gastric tube in conscious rats after 12 h fast. Adipocyte size was assessed by light microscope after collagenase digestion. Hypothalamic arcuate (ARC) and paraventricular nuclei (PVN) were isolated by the punching technique. Target mRNAs were quantified by real-time PCR with the use of TaqMan probes and primers. Serum hormones (leptin, ghrelin, adiponectin, visfatin and insulin) were assayed by specific RIAs . RESULTS: During the experimental period SHF rats had the same body weight gain and caloric intake as CN rats. At the age of 8 weeks SHF rats showed increased epididymal fat mass and adipocyte volume, impaired glucose tolerance, normal basal fasting insulin, visfatin, and ghrelin level, but decreased adiponectin and high leptin level. In the ARC, the SHF rats showed increased expression of mRNA for orexigenic neuropeptide Y (NPY), agouti-related protein (AgRP) and anorexigenic pro-inflammatory cytokine IL-6. In the PVN, the SHF rats showed increased expression of mRNA for anorexigenic melanocortin 4 receptor (MC4R) and IL-6. CONCLUSION: Overexpression of orexigenic NPY and AgRP in the ARC indicates leptin resistance in SHF rats. The increased expression of MC4R in PVN points to the activation of melanocortin anorexigenic system which, along with increased hypothalamic IL-6, might prevent the animals from overfeeding. Higher adiposity in these rats results from the high fat-diet composition and not from increased caloric intake. Furthermore, enhanced leptin production appears the main factor indicating the predisposition to autoimmunity in these overfed rats.
- MeSH
- adiponektin krev MeSH
- adipozita MeSH
- AGRP protein genetika metabolismus MeSH
- analýza rozptylu MeSH
- bílá tuková tkáň cytologie MeSH
- bílé tukové buňky MeSH
- dietní tuky aplikace a dávkování MeSH
- energetický příjem MeSH
- exprese genu MeSH
- ghrelin krev MeSH
- interleukin-6 genetika metabolismus MeSH
- inzulin krev MeSH
- krysa rodu rattus MeSH
- leptin krev MeSH
- messenger RNA metabolismus MeSH
- neuropeptid Y genetika metabolismus MeSH
- nikotinamidfosforibosyltransferasa krev MeSH
- nucleus arcuatus hypothalami metabolismus MeSH
- nucleus paraventricularis hypothalami metabolismus MeSH
- obezita genetika metabolismus MeSH
- plocha pod křivkou MeSH
- porucha glukózové tolerance MeSH
- potkani inbrední LEW MeSH
- receptor melanokortinový typ 4 genetika metabolismus MeSH
- regulace chuti k jídlu fyziologie MeSH
- stárnutí MeSH
- stravovací zvyklosti MeSH
- tělesná hmotnost MeSH
- velikost buňky MeSH
- velikost vrhu MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
BACKGROUND: CART (cocaine- and amphetamine-regulated transcript) peptide and cholecystokinin (CCK) are neuromodulators involved in feeding behavior. This study is based on previously found synergistic effect of leptin and CCK on food intake and our hypothesis on a co-operation of the CART peptide and CCK in food intake regulation and Fos activation in their common targets, the nucleus tractus solitarii of the brainstem (NTS), the paraventricular nucleus (PVN), and the dorsomedial nucleus (DMH) of the hypothalamus. RESULTS: In fasted C57BL/6 mice, the anorexigenic effect of CART(61-102) in the doses of 0.1 or 0.5 microg/mouse was significantly enhanced by low doses of CCK-8 of 0.4 or 4 microg/kg, while 1 mg/kg dose of CCK-A receptor antagonist devazepide blocked the effect of CART(61-102) on food intake. After simultaneous administration of 0.1 microg/mouse CART(61-102) and of 4 microg/kg of CCK-8, the number of Fos-positive neurons in NTS, PVN, and DMH was significantly higher than after administration of each particular peptide. Besides, CART(61-102) and CCK-8 showed an additive effect on inhibition of the locomotor activity of mice in an open field test. CONCLUSION: The synergistic and long-lasting effect of the CART peptide and CCK on food intake and their additive effect on Fos immunoreactivity in their common targets suggest a co-operative action of CART peptide and CCK which could be related to synergistic effect of leptin on CCK satiety
- MeSH
- antagonisté hormonů farmakologie MeSH
- benzodiazepinony farmakologie MeSH
- devazepid farmakologie MeSH
- fenylmočovinové sloučeniny farmakologie MeSH
- financování organizované MeSH
- hubenost MeSH
- injekce intraperitoneální MeSH
- injekce intraventrikulární MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- neurony metabolismus účinky léků MeSH
- nucleus dorsomedialis hypothalami fyziologie účinky léků MeSH
- nucleus paraventricularis hypothalami fyziologie účinky léků MeSH
- nucleus solitarius fyziologie účinky léků MeSH
- pátrací chování fyziologie účinky léků MeSH
- peptidové fragmenty farmakologie MeSH
- proteiny nervové tkáně farmakologie MeSH
- protoonkogenní proteiny c-fos metabolismus MeSH
- receptor cholecystokininu A antagonisté a inhibitory MeSH
- receptor cholecystokininu B antagonisté a inhibitory MeSH
- regulace chuti k jídlu fyziologie účinky léků MeSH
- sinkalid farmakologie MeSH
- synergismus léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- MeSH
- finanční podpora výzkumu jako téma MeSH
- hormon uvolňující thyreotropin fyziologie sekrece MeSH
- hypotyreóza chemicky indukované MeSH
- kolchicin farmakologie terapeutické užití MeSH
- krysa rodu rattus MeSH
- nucleus paraventricularis hypothalami účinky léků MeSH
- techniky in vitro MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- MeSH
- finanční podpora výzkumu jako téma MeSH
- imunohistochemie MeSH
- neurony metabolismus MeSH
- nucleus paraventricularis hypothalami cytologie metabolismus MeSH
- nucleus supraopticus metabolismus MeSH
- oxytocin metabolismus MeSH
- protoonkogenní proteiny c-fos biosyntéza MeSH
- vasopresiny metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- MeSH
- aferentní nervové dráhy fyziologie MeSH
- eferentní nervové dráhy fyziologie MeSH
- finanční podpora výzkumu jako téma MeSH
- fyziologický stres patofyziologie MeSH
- hypothalamus anatomie a histologie fyziologie MeSH
- mozeček anatomie a histologie fyziologie MeSH
- neurotransmiterové látky fyziologie MeSH
- nucleus paraventricularis hypothalami fyziologie MeSH
- Publikační typ
- přehledy MeSH