Showing papers on "Area postrema published in 2009"
TL;DR: It is demonstrated that leptin signaling in the caudal NTS increases SNA to the kidney but not to the brown adipose tissue, which strengthens the concept of a distributed brain network of leptin action and demonstrates that these distributed brain sites can mediate contrasting sympathetic responses to leptin.
Abstract: The hypothalamic arcuate nucleus was initially regarded as the principal site of leptin action, but there is increasing evidence for functional leptin receptors in extrahypothalamic sites, including the nucleus tractus solitarii (NTS). We demonstrated previously that arcuate injection of leptin increases sympathetic nerve activity (SNA) to brown adipose tissue and kidney. In this study, we tested the hypothesis that leptin signaling in the NTS affects sympathetic neural outflow. Using a stereotaxic device in anesthetized rats, we microinjected leptin (0.25 to 1.00 g) or saline into the NTS while recording SNA to kidney and brown adipose tissue. Microinjection of leptin into the commissural and medial subnuclei of the caudal NTS at the level of the area postrema in Sprague-Dawley rats produced a dose-related increase in renal SNA (11215% with leptin 1 g; n7; P0.001) but did not increase SNA to brown adipose tissue (1512%; P value not significant). This effect depended on intact functional leptin receptors, because it was not observed in Zucker obese rats that have a missense mutation in the leptin receptor. Rostral NTS injection of leptin failed to increase SNA, indicating that leptin signaling in the NTS is probably confined to the caudal NTS at the level of the area postrema. In summary, this study demonstrates that leptin signaling in the caudal NTS increases SNA to the kidney but not to the brown adipose tissue. The study strengthens the concept of a distributed brain network of leptin action and demonstrates that these distributed brain sites can mediate contrasting sympathetic responses to leptin. (Hypertension. 2009;53(part 2):375-380.)
125 citations
TL;DR: A framework by which the temporal effects of appetite modulating agents can be recorded simultaneously within hypothalamic and brainstem feeding centres is provided, suggesting the anorexigenic effects of GLP-1 may be in part transmitted via nausea circuits.
89 citations
TL;DR: This study provides a detailed analysis of the cellular localization of BBB proteins in the AP and NTS and shows the existence of vessels in the dorsomedial aspect of the NTS that lack immunoreactivity for the BBB markers EBA and TfR.
86 citations
TL;DR: Double immunohistochemistry and triple labeling showed that a portion of the nesfatin-1 neurons activated in response to LPS within the NTS are catecholaminergic since they co-express tyrosine hydroxylase (TH).
Abstract: Recently, a novel factor with anorexigenic properties was identified and called nesfatin-1. This protein (82 aac) is not only expressed in peripheral organs but it is also found in neurons located in specific structures including the hypothalamus and the brainstem, two sites strongly involved in food intake regulation. Here, we studied whether some of the neurons that become activated following an injection of an anorectic dose of lipopolysaccharides (LPS) exhibit a nesfatin-1 phenotype. To this end, we used double immunohistochemistry to target the expression of the immediate-early gene c-fos and of nesfatin-1 on coronal frozen sections of the rat brain. The number of c-Fos+/nesfatin-1+ neurons was evaluated in the immunosensitive structures reported to contain nesfatin-1 neurons; i.e. paraventricular hypothalamic nucleus (PVN), supraoptic nucleus (SON), arcuate nucleus (ARC) and nucleus of the solitary tract (NTS). LPS strongly increased the number of c-Fos+/nesfatin-1+ neurons in the PVN, SON and NTS, and to a lesser extent in the ARC. Triple labeling showed that a portion of the nesfatin-1 neurons activated in response to LPS within the NTS are catecholaminergic since they co-express tyrosine hydroxylase (TH). Our data therefore indicate that a portion of nesfatin-1 neurons of both the hypothalamus and brainstem are sensitive to peripheral inflammatory signals, and provide the first clues suggesting that centrally released nesfatin-1 may contribute to the neural mechanisms leading to endotoxaemic anorexia.
75 citations
TL;DR: Peripheral administration of pancreatic polypeptide (PP) induced Y4 receptor-dependent c-Fos expression in brain stem, hypothalamus and amygdala, and PP released peripherally from the pancreas in response to food intake, may act not only as a satiety signal but also modulate anxiety-related locomotion.
67 citations
TL;DR: Ghrelin, a peptide hormone secreted from the stomach, is known to have a potent appetite-stimulating activity as discussed by the authors, and it has been shown that area postrema (AP), a caudal brain stem center that l...
Abstract: Ghrelin, a peptide hormone secreted from the stomach, is known to have a potent appetite-stimulating activity. Recently, it has been shown that area postrema (AP), a caudal brain stem center that l...
52 citations
TL;DR: Results support published acute phase data in other species, and are the first describing Fos-IR following delayed phase emesis, which suggest overlapping but separate mechanisms are invoked for each phase, which are sensitive to antiemetic effects of Delta(9)-THC mediated by CB(1) receptors.
41 citations
TL;DR: A developing literature that shows receptors for, and functional actions of, gastrointestinal hormones such as amylin, cholecystokinin, ghrelin and peptide YY in the area postrema and subfornical organ are reviewed, suggesting potentially significant roles for the sensory CVOs in the regulation of energy balance.
Abstract: A variety of circulating signals provide essential information to the central nervous system (CNS) regarding nutritional status. The gastrointestinal system produces many such molecules that are now known to have profound effects on feeding behavior and the control of metabolism as a consequence of their ability to regulate the neural circuitry involved in metabolic homeostasis. Although many of these substances have been suggested to directly access such brain centers, their lipophobic characteristics suggest that alternative mechanisms should be considered. In this paper, we consider one such alternative, namely, that a specialized group of CNS structures collectively known as the sensory circumventricular organs (CVOs), which are not protected by the normal blood-brain barrier, may play important roles in such blood to brain communications. Specifically, we review a developing literature that shows receptors for, and functional actions of, gastrointestinal hormones such as amylin, cholecystokinin, ghrelin and peptide YY in the area postrema and subfornical organ. Collectively, these observations suggest potentially significant roles for the sensory CVOs in the regulation of energy balance.
37 citations
TL;DR: Data suggest the dorsal vagal complex is part of a common pathway for a variety of distinct emetogens, but there are central emetic substrates, both medullary and diencephalic, that can be accessed without directly stimulating the area postrema.
Abstract: Research on the mechanisms of emesis has implicated multiple neurotransmitters via both central (dorsal vagal complex) and peripheral (enteric neurons and enterochromaffin cells) anatomical substrates. Taking advantage of advances in receptor-specific agonists, and utilizing Fos expression as a functional activity marker, this study demonstrates a strong, but incomplete, overlap in anatomical substrates for a variety of emetogens. We used cisplatin and specific agonists to 5-HT(3) serotonergic, D(2)/D(3) dopaminergic, and NK(1) tachykininergic receptors to induce vomiting in the least shrew (Cryptotis parva), and quantified the resulting Fos expression. The least shrew is a small mammal whose responses to emetic challenges are very similar to its human counterparts. In all cases, the enteric nervous system, nucleus of the solitary tract, and dorsal motor nucleus of the vagus demonstrated significantly increased Fos immunoreactivity (Fos-IR). However, Fos-IR induction was notably absent from the area postrema following the dopaminergic and NK(1) receptor-specific agents. Two brain nuclei not usually discussed regarding emesis, the dorsal raphe nucleus and paraventricular thalamic nucleus, also demonstrated increased emesis-related Fos-IR. Taken together, these data suggest the dorsal vagal complex is part of a common pathway for a variety of distinct emetogens, but there are central emetic substrates, both medullary and diencephalic, that can be accessed without directly stimulating the area postrema.
37 citations
TL;DR: Intermediate to strong immunoreaction was observable in presumptive DA cells in the mesencephalic reticular formation, substantia nigra, and ventral tegmental area of Tsai, as well as in presumptive noradrenergic (NA) cells, which were aggregated in the locus coeruleus and dispersed in the subcoeruleus nuclei.
37 citations
TL;DR: The data presented here identify a novel mechanism through which a serotonin receptor agonist acting in the caudal brainstem may regulate ingestive behavior.
TL;DR: The studies identify the mNTS as a new CNS site which adiponectin may act to influence central autonomic processing and suggest that such effects may occur as a direct result of the ability of this adipokine to modulate the excitability of discrete groups of neurons in the NTS.
TL;DR: Chronic immobilization stress induced a significant decrease of the total neurosphere number per rat DVC in both primary and secondary cultures, indicating that intrinsic neural stem cell frequency was decreased by chronic stress in DVC tissue.
TL;DR: The area postrema can act as a sensor for circulating TNF-alpha and IL-1beta, or for locally produced cytokines and NO during infection and inflammation, in distinct populations of cells investigated in a primary microculture of the rat AP.
TL;DR: Gingerol has good activity against cisplatin-induced emesis in minks possibly by inhibiting central or peripheral increase of 5-HT, DA and substance P.
Abstract: Objective
To investigate the antiemetic effect of gingerol and its multi-targets effective mechanism on 5-hydroxytryptamine (5-HT), dopamine (DA) and substance P (SP). The antiemetic effect of gingerol was investigated on a vomiting model of mink induced by cisplatin (7.5 mg · kg−1, i.p.) in 6 h observation. The levels of 5-HT, DA and distribution of substance P in the area postrema and ileum were measured by high performance liquid chromatography (HPLC) and immunohistochemistry respectively. The frequency of cisplatin induced retching and vomiting was significantly reduced by pretreatment with gingerol in a dose-dependent manner (P<0.05). Cisplatin produced a significant increase in 5-HT and DA levels in the area postrema and ileum of minks (P<0.05), and this increase was significantly inhibited by gingerol in a dose-dependent manner (P<0.05). Substance P-immunoreactive was mainly situated in the mucosa and submucosa of ileum as well as in the neurons of area postrema, and gingerol markedly suppressed the increase immunoreactivity of substance P induced by cisplatin in a dose-dependent manner (P<0.05). Gingerol has good activity against cisplatin-induced emesis in minks possibly by inhibiting central or peripheral increase of 5-HT, DA and substance P.
TL;DR: It is suggested that brainstem areas including ascending catetholaminergic A2/C2 neurons could play a role in rimonabant-induced inhibition of food intake by increasing c-Fos protein expression in TH-positive neurons.
TL;DR: It is suggested that a defined portion of cisplatin-induced Fos expression is dependent on vagal input, with a majority of this response determined by either direct action of cis platin or humoral factors on the CNS.
Abstract: Anticancer agents such as cisplatin stimulate nausea, vomiting, and behaviors indicative of malaise. Rats and mice, and probably all rodents, do not possess a vomiting response, and their ingestion of kaolin clay (a pica response) has been used as an index of malaise. Similar to the action of cisplatin on emesis in vomiting species, in the rat cisplatin activates vagal afferent fibers, and cisplatin-induced kaolin intake is largely dependent on an intact abdominal vagus. Cisplatin also stimulates Fos expression in the rat brain in areas known to play a role in emesis in other species, but it is not known whether vagal input is required for this CNS activation. In the present study, rats were given abdominal vagotomy or sham operation to test the role of an intact vagus on cisplatin-induced Fos expression 6 h after injection with saline or cisplatin (6 mg/kg, ip). Cisplatin treatment produced Fos expression in the area postrema and multiple levels of the nucleus of the solitary tract (NTS) of sham-operated rats. Vagotomy reduced cisplatin-induced Fos expression in the caudal and middle levels of the NTS and central amygdala. Furthermore, cisplatin did not significantly alter Fos expression in the spinal cord (T8–T10) before or after vagotomy. These results suggest that a defined portion of cisplatin-induced Fos expression is dependent on vagal input, with a majority of this response determined by either direct action of cisplatin or humoral factors on the CNS.
TL;DR: It is hypothesised that Ob‐R positive glial cells of the DVC participate in the transport of leptin into the brainstem and thus contribute to regulation of energy homeostasis.
Abstract: Leptin, an adipocyte-derived hormone, regulates food intake and body weight by acting principally on the hypothalamus, which displays the highest expression of leptin receptor (Ob-R). Nevertheless, other regions of the brain express Ob-R and constitute leptin's target sites. The dorsal vagal complex (DVC), an integrative centre of autonomic functions located in the caudal brainstem, is one of these structures. Leptin, by acting through the DVC, affects autonomic and neuroendocrine functions, such as control of food intake and gastric motility. In the present study, we observed Ob-R labelling within the DVC in cells that correspond to neuronal cell bodies. We showed for the first time Ob-R expression in a subpopulation of glial fibrillary acid protein positive cells located at the border between the area postrema and the nucleus tractus solitarius (NTS). These glial cells exhibit an atypical morphology consisting of unbranched processes that radiate rostro-caudally from the fourth ventricle wall. In vitro, the glial cells exhibited both long and short Ob-R expression with a preferential expression of the Ob-Ra and-f isoforms. Interestingly, using i.v and i.c.v. injection of the fluorescent tracer hydroxystilbamidine, we provided evidence that these cells may constitute a diffusion barrier which might regulate entry of molecules into the NTS. Finally, modulation of energy status, by acute or chronic reduction of food intake, modulated especially the short Ob-R isoforms in the DVC. In the light of these results, we hypothesise that Ob-R positive glial cells of the DVC participate in the transport of leptin into the brainstem and thus contribute to regulation of energy homeostasis.
TL;DR: Data suggest that, in contrast to the acute emetic response triggered by cisplatin, the delayed phase does not rely on abdominal visceral afferents but is mediated via the area postrema.
TL;DR: Central neuronal activation following inflammation after systemic LPS is modulated by cyclooxygenase and NO pathways, which may set the stage for efferent vagal modulation of intestinal inflammation.
Abstract: Introduction Inflammation during systemic lipopolysaccharide (LPS) seems to be modulated by the CNS via afferent and efferent vagal pathways. We hypothesized that similar to systemic inflammation, local LPS in the gut lumen may also activate central neurons and aimed to identify potential molecular mechanisms. Methods Male Wistar rats were equipped with an exteriorized canula in the proximal jejunum. LPS or vehicle were administered into the jejunum (10 mg ml − 1 ). For further study of molecular mechanisms, LPS or vehicle were administered systemically (1 mg kg − 1 ). Brain stem activation was quantified by Fos-immunohistochemistry in the vagal nucleus of the solitary tract (NTS) and the Area postrema which is exposed to systemic circulation. Serum LPS concentrations were also determined. Results Jejunal LPS exposure entailed 91 ± 12 ( n = 7) Fos-positive neurons in the NTS compared to 39 ± 9 in controls ( n = 6; p n = 6) and vehicle 52 ± 6 Fos-positive neurons ( n = 7; p − 1 ; p > 0.05 versus vehicle controls) and increased to 242 ± 66 following the iNOS-inhibitor Aminoguanidine (15 mg kg − 1 ; p n = 6) neurons were counted in animals pretreated with systemic LPS compared to 14 ± 4 in controls ( n = 7, p Conclusions Central neuronal activation following inflammation after systemic LPS is modulated by cyclooxygenase and NO pathways. Local exposure to bacterial LPS in the gut lumen activates the NTS which may set the stage for efferent vagal modulation of intestinal inflammation.
TL;DR: The results indicate that the neuronal hyperactivity of DMV, NA, NTS and AP, the primary center that control gastric functions, especially DMV and NA, may play an important role in the disorders of gastric motility and secretion induced by RWIS.
Abstract: Restraint water-immersion stress (RWIS) of rats induces vagally-mediated gastric dysfunction. The present work explored the effects of different durations of RWIS on neuronal activities of the dorsal vagal complex (DVC) and the nucleus ambiguous (NA) in rats. Male Wistar rats were exposed to RWIS for 0, 30, 60, 120, or 180 min. Then, a c-Fos immunoperoxidase technique was utilized to assess neuronal activation. Resumptively, c-Fos expression in DVC and NA peaked at 60 min of stress, subsequently decreased gradually with increasing durations of RWIS. Interestingly, the most intense c-Fos expression was observed in the dorsal motor nucleus of the vagus (DMV) during the stress, followed by NA, nucleus of solitary tract (NTS) and area postrema (AP). The peak of c-Fos expression in caudal DMV appeared at 120 min of the stress, slower than that in rostral and intermediate DMV. The c-Fos expression in intermediate and caudal NTS was significantly more intense than that in rostral NTS. These results indicate that the neuronal hyperactivity of DMV, NA, NTS and AP, the primary center that control gastric functions, especially DMV and NA, may play an important role in the disorders of gastric motility and secretion induced by RWIS.
TL;DR: It is concluded that unmyelinated AEN terminal projections are involved in the activation of neurons in the MDH and ventrolateral medulla that participate in the nasopharyngeal response in the rat.
TL;DR: It is confirmed that in rats with a F344 background, CCK-1R mediatesCCK-8-induced inhibition of food intake and Fos activation in the hindbrain and demonstrated that selective genetic ablation of CCK1R is not associated with altered meal patterns, hyperphagia, or excessive weight gain on a palatable diet.
TL;DR: Saline intake remained elevated in lesioned rats when the tests were repeated 6 and 14 days after the lesion, and water intake in these two tests was increased as well, a possible explanation for the increased saline intake in rats with commissural NTS lesions could be a reduced gastrointestinal feedback inhibition.
Abstract: Ablation of the area postrema/caudal nucleus of the tractus solitarius (NTS) complex increases sodium intake, but the effect of selective lesions of the caudal NTS is not known. We measured depletion-induced sodium intake in rats with electrolytic lesions of the commissural NTS that spared the area postrema. One day after the lesion, rats were depleted of sodium with furosemide (10 mg/kg body weight, sc) and then had access to water and a sodium-deficient diet for 24 h when 1.8% NaCl was offered. Water and saline intakes were measured for 2 h. Saline intake was higher in lesioned than in sham-lesioned rats (mean +/- SEM: 20 +/- 2 vs 11 +/- 3 mL/2 h, P < 0.05, N = 6-7). Saline intake remained elevated in lesioned rats when the tests were repeated 6 and 14 days after the lesion, and water intake in these two tests was increased as well. Water intake seemed to be secondary to saline intake both in lesioned and in sham-lesioned rats. A second group of rats was offered 10% sucrose for 2 h/day before and 2, 7, and 15 days after lesion. Sucrose intake in lesioned rats was higher than in sham-lesioned rats only 7 days after lesioning. A possible explanation for the increased saline intake in rats with commissural NTS lesions could be a reduced gastrointestinal feedback inhibition. The commissural NTS is probably part of a pathway for inhibitory control of sodium intake that also involves the area postrema and the parabrachial nucleus.
TL;DR: HSD2 neurons receive an input mainly from the stomach and these results are considered as potential sites affecting sodium intake.
TL;DR: The results suggest that clonidine exerts its hypotensive effect in the rat via a stimulation of histamine H2-receptors in, or in the vicinity of, the area postrema.
Abstract: . In urethane-anaesthetized rats clonidine was administered intravenously (i.v.), intra-cerebroventricularly (Lev.) or onto the surface of the area postrema which protrudes into the fourth cerebral ventricle. In each Instance clonidine induced a dose-dependent lowering of the blood pressure. The region of the area postrema appears to be the most sensitive site for the action of clonidine so far studied. In order to obtain similar blood pressure effects, approximately 8 times higher amounts were needed i.c.v., and about 80 times higher amounts i.v., than onto the surface of the area postrema.
A pretreatment of the rats with the specific histamine H2-receptor blocking drug, metiamide (4.5 μmoles/rat i.c.v.) shifted the dose-response curve of clonidine (i.c.v.) to the right.
The results suggest that clonidine exerts its hypotensive effect in the rat via a stimulation of histamine H2-receptors in, or in the vicinity of, the area postrema.
TL;DR: Results do not support the hypothesis that a greater attenuation of the hypotensive effects of losartan would be observed in rats with dual lesions, but suggest redundancy and compensatory roles of the AP and SFO in basal cardiovascular control.
TL;DR: The organization and chemical development of the area postrema (AP) in the macaque monkey was studied by immunohistochemistry with conventional and confocal microscopy from day 40 of gestation to adulthood, consistent with the view that catecholaminergic cells in AP are the earliest members of the A2 noradrenergic group.
TL;DR: The results suggest that the PDA may play an important role in the regulation of feeding behavior, at least partly by modulating the circulating leptin, and that the caudal and intermediate parts of the NST, AP, external lateral PBN, Arc, and CeA probably participate in this regulation.
01 Feb 2009
TL;DR: The causes of postoperative nausea and vomiting are legion, as illustrated by Figure CN1, and anti-emetic therapy is most effective when directed at the likely origin this paper.
Abstract: Many drugs act on the central nervous system (CNS), with specific aims in mind. While certain categories of drugs are considered elsewhere (anaesthetic gases and vapours in Section 3, Chapter 5, hypnotics and intravenous agents in Chapter 6) other drugs acting on the CNS have been grouped here. Anti-emetic agents are considered in detail, with specific pharmacology of individual agents to reflect their direct relevance to the practice of anaesthesia. Anti-emetic agents The causes of nausea and vomiting (NV) are legion, as illustrated by Figure CN1, and anti-emetic therapy is most effective when directed at the likely origin. Postoperative nausea and vomiting (PONV) is a specific entity. Its treatment is more appropriately directed when other risk factors are considered, and these are summarised in Figure CN2. Two distinct sites in the CNS, the vomiting centre and the chemoreceptor trigger zone, are implicated in the causes of NV. The chemoreceptor trigger zone lies in the area postrema outside the blood–brain barrier and possesses dopaminergic (D 2 ) and serotonergic (5-hydroxytryptamine, 5-HT 3 ) receptors. In contrast, the vomiting centre is a complex entity located in the dorsolateral reticular formation of the brain stem that possesses 5-HT 3 , D 2 and muscarinic (M 3 ) receptors. Histaminic (H 1 ) and neurokinin (NK 1 ) receptors are located in the nucleus of the tractus solitarius, which integrates afferent signals associated with emesis. The interaction of various drugs with these sites is shown in Figure CN3.