Plasma hormone levels and central c-Fos expression in ferrets after systemic administration of cholecystokinin

2001 ◽  
Vol 281 (4) ◽  
pp. R1243-R1255 ◽  
Author(s):  
I. Billig ◽  
B. J. Yates ◽  
L. Rinaman
Keyword(s):  
Brain Stem ◽  
Area Postrema ◽  
Hormone Secretion ◽  
Early Gene ◽  
Central Nucleus ◽  
Ventrolateral Medulla ◽  
Pituitary Hormone ◽  
Bed Nucleus ◽  
Fos Expression ◽  
Glucagon Like Peptide 1

Posterior pituitary hormone secretion and central neural expression of the immediate-early gene product c-Fos was examined in adult ferrets after intravenous administration of CCK octapeptide. Pharmacological doses of CCK (1, 5, 10, or 50 μg/kg) did not induce emesis, but elicited behavioral signs of nausea and dose-related increases in plasma vasopressin (AVP) levels without significant increases in plasma oxytocin (OT) levels. CCK activated neuronal c-Fos expression in several brain stem viscerosensory regions, including a dose-related activation of neurons in the dorsal vagal complex (DVC). Activated brain stem neurons included catecholaminergic and glucagon-like peptide-1-positive cells in the DVC and ventrolateral medulla. In the forebrain, activated neurons were prevalent in the paraventricular and supraoptic nuclei of the hypothalamus and also were observed in the central nucleus of the amygdala and bed nucleus of the stria terminalis. Activated hypothalamic neurons included cells that were immunoreactive for AVP, OT, and corticotropin-releasing factor. Comparable patterns of brain stem and forebrain c-Fos activation were observed in ferrets after intraperitoneal injection of lithium chloride (LiCl; 86 mg/kg), a classic emetic agent. However, LiCl activated more neurons in the area postrema and fewer neurons in the nucleus of the solitary tract compared with CCK. Together with results from previous studies in rodents, our findings support the view that nauseogenic treatments activate similar central neural circuits in emetic and nonemetic species, despite differences in treatment-induced emesis and pituitary hormone secretion.

Medullary c-Fos activation in rats after ingestion of a satiating meal

1998 ◽  
Vol 275 (1) ◽  
pp. R262-R268 ◽  
Author(s):  
L. Rinaman ◽  
E. A. Baker ◽  
G. E. Hoffman ◽  
E. M. Stricker ◽  
J. G. Verbalis
Keyword(s):  
Area Postrema ◽  
Vagal Afferents ◽  
Early Gene ◽  
Ventrolateral Medulla ◽  
Gastric Distension ◽  
Neural Activation ◽  
Food Ingestion ◽  
Catecholaminergic Neurons ◽  
Medial Nucleus ◽  
Fos Expression

The distribution and chemical phenotypes of hindbrain neurons that are activated in rats after food ingestion were examined. Rats were anesthetized and perfused with fixative 30 min after the end of 1-h meals of an unrestricted or rationed amount of food, or after no meal. Brain sections were processed for localization of the immediate-early gene product c-Fos, a marker of stimulus-induced neural activation. Hindbrain c-Fos expression was low in rats that ate a rationed meal or no meal. Conversely, c-Fos was prominent in the medial nucleus of the solitary tract (NST) and area postrema in rats that ate to satiety. There was a significant positive correlation between postmortem weight of gastric contents and the proportion of NST catecholaminergic neurons expressing c-Fos. Cells in the ventrolateral medulla (VLM) were not activated in rats after food ingestion, in contrast with previous findings that stimulation of gastric vagal afferents with anorexigenic doses of cholecystokinin activates c-Fos expression in both NST and VLM catecholaminergic cells. These findings indicate that anatomically distinct subsets of hindbrain catecholaminergic neurons are activated in rats after food ingestion and that activation of these cells is quantitatively related to the magnitude of feeding-induced gastric distension.

scholarly journals Central Fos expression and conditioned flavor avoidance in rats following intragastric administration of bitter taste receptor ligands

2009 ◽  
Vol 296 (3) ◽  
pp. R528-R536 ◽  
Author(s):  
Shuzhen Hao ◽  
Michelle Dulake ◽  
Elvis Espero ◽  
Catia Sternini ◽  
Helen E. Raybould ◽  
...  
Keyword(s):  
Oral Cavity ◽  
Brain Stem ◽  
Bitter Taste ◽  
Taste Receptor ◽  
Central Nucleus ◽  
Ventrolateral Medulla ◽  
Intragastric Administration ◽  
Behavioral Correlate ◽  
Fos Expression ◽  
Intragastric Gavage

G protein-coupled receptors that signal bitter taste (T2Rs) are expressed in the mucosal lining of the oral cavity and gastrointestinal (GI) tract. In mice, intragastric infusion of T2R ligands activates Fos expression within the caudal viscerosensory portion of the nucleus of the solitary tract (NTS) through a vagal pathway (Hao S, Sternini C, Raybould HE. Am J Physiol Regul Integr Comp Physiol 294: R33–R38, 2008). The present study was performed in rats to further characterize the distribution and chemical phenotypes of brain stem and forebrain neurons activated to express Fos after intragastric gavage of T2R ligands, and to determine a potential behavioral correlate of this central neural activation. Compared with relatively low brain stem and forebrain Fos expression in control rats gavaged intragastrically with water, rats gavaged intragastrically with T2R ligands displayed significantly increased activation of neurons within the caudal medial (visceral) NTS and caudal ventrolateral medulla, including noradrenergic neurons, and within the lateral parabrachial nucleus, central nucleus of the amygdala, and paraventricular nucleus of the hypothalamus. A behavioral correlate of this Fos activation was evidenced when rats avoided consuming flavors that previously were paired with intragastric gavage of T2R ligands. While unconditioned aversive responses to bitter tastants in the oral cavity are often sufficient to inhibit further consumption, a second line of defense may be provided postingestively by ligand-induced signaling at GI T2Rs that signal the brain via vagal sensory inputs to the caudal medulla.

Fos expression in brain stem nuclei of pregnant rats after hydralazine-induced hypotension

1999 ◽  
Vol 277 (2) ◽  
pp. R532-R540 ◽  
Author(s):  
Kathleen S. Curtis ◽  
J. Thomas Cunningham ◽  
Cheryl M. Heesch
Keyword(s):  
Area Postrema ◽  
Virgin Female ◽  
Female Rats ◽  
Ventrolateral Medulla ◽  
Pregnant Rats ◽  
Induced Hypotension ◽  
Central Response ◽  
Vehicle Treatment ◽  
Fos Expression ◽  
The Brain

Fos and dopamine β-hydroxylase immunoreactivity were evaluated in the brain stems of 21-day pregnant and virgin female rats injected with either hydralazine (HDZ; 10 mg/kg iv) or vehicle. HDZ produced significant hypotension in both groups, although baseline blood pressure was lower in pregnant rats (96 ± 2.5 mmHg) than in virgin female rats (121 ± 2.8 mmHg). There were no differences in Fos immunoreactivity in the brain stems of pregnant and virgin female rats after vehicle treatment. HDZ-induced hypotension significantly increased Fos expression in both groups; however, the magnitude of the increases differed in the caudal ventrolateral medulla (CVL), the area postrema (AP), and the rostral ventrolateral medulla (RVL). Fos expression after HDZ in pregnant rats was augmented in noncatecholaminergic neurons of the CVL but was attenuated in the AP and in noncatecholaminergic neurons in the RVL. These results are consistent with differences in the sympathetic response to hypotension between pregnant and virgin female rats and indicate that the central response to hypotension may be different in pregnant rats.

CGRP infusion in unanesthetized rats increases expression of c-Fos in the nucleus tractus solitarius and caudal ventrolateral medulla, but not in the trigeminal nucleus caudalis

Cephalalgia ◽  
2014 ◽  
Vol 35 (3) ◽  
pp. 220-233 ◽  
Author(s):  
Deepak K Bhatt ◽  
Roshni Ramachandran ◽  
Sarah LT Christensen ◽  
Saurabh Gupta ◽  
Inger Jansen-Olesen ◽  
...  
Keyword(s):  
Protein Expression ◽  
Brain Stem ◽  
Dura Mater ◽  
Nucleus Tractus Solitarius ◽  
Early Gene ◽  
Ventrolateral Medulla ◽  
Trigeminal Nucleus ◽  
Caudal Ventrolateral Medulla ◽  
Trigeminal Nucleus Caudalis ◽  
The Brain

Background and aims Calcitonin gene-related peptide (CGRP) and glyceryl trinitrate (GTN) infusion in migraineurs provokes headache resembling spontaneous migraine, and CGRP receptor antagonists are effective in the treatment of acute migraine. We hypothesized that CGRP infusion would increase molecular markers of neuronal activation in migraine-relevant tissues of the rat. Methods CGRP was infused intravenously (i.v.) in freely moving rats to circumvent factors like anesthesia, acute surgery and severe hypotension, the three confounding factors for c-Fos expression. The trigeminal nucleus caudalis (TNC) was isolated at different time points after CGRP infusion. The level of c-Fos mRNA and protein expression in TNC were analyzed by qPCR and immunohistochemistry. c-Fos-stained nuclei were also counted in the nucleus tractus solitarius (NTS) and caudal ventrolateral medulla (CVLM), integrative sites in the brain stem for processing cardiovascular signals. We also investigated Zif268 protein expression (another immediate early gene) in TNC. The protein expression of p-ERK, p-CREB and c-Fos was analyzed in dura mater, trigeminal ganglion (TG) and TNC samples using Western blot. Results CGRP infusion caused a significant dose-dependent fall in mean arterial blood pressure. No significant activation of c-Fos in the TNC at mRNA and protein levels was observed after CGRP infusion. A significant increase in c-Fos protein was observed in the NTS and CVLM in the brain stem. Zif268 expression in the TNC was also not changed after CGRP infusion. p-ERK was increased in the dura mater 30 minutes after CGRP infusion. Conclusion CGRP infusion increased the early expression of p-ERK in the dura mater but did not increase c-Fos and Zif268 expression in the TNC. The rats may, thus, differ from migraine patients, in whom infusion of CGRP caused headache and a delayed migraine attack. The rat CGRP infusion model with c-Fos or Zif268 as neuronal pain markers in TNC is unsuitable for antimigraine drug testing.

Effect of vagal and splanchnic nerve section on Fos expression in ferret brain stem after emetic stimuli

1996 ◽  
Vol 271 (1) ◽  
pp. R228-R236 ◽  
Author(s):  
F. M. Boissonade ◽  
J. S. Davison
Keyword(s):  
Vagus Nerve ◽  
Brain Stem ◽  
Area Postrema ◽  
Splanchnic Nerve ◽  
Vagal Afferents ◽  
Sham Operation ◽  
Relative Importance ◽  
Solitary Tract ◽  
Nerve Section ◽  
Fos Expression

Previous studies have demonstrated that intraduodenal hypertonic saline (IHS) induces dense Fos expression within two regions of the ferret dorsal vagal complex (DVC): the area postrema (AP) and the medial subnucleus of the nucleus of the solitary tract (mn). The aims of the present experiments were to determine the peripheral pathways involved in excitation of DVC neurons after IHS and the relative importance of mn and AP excitation in the emetic response to this stimulus. The emetic response and the distribution of Fos were examined after IHS in animals that had received either vagotomy alone, vagotomy and splanchnic nerve section, or sham operation. The emetic response was studied in both awake and anesthetized animals, and Fos induction was studied in anesthetized animals. Vagotomy alone or combined with splanchnic nerve section abolished the emetic response and the area of dense labeling within the mn and reduced but did not abolish the labeling in the AP. It was concluded that both the emetic reflex and the dense expression of Fos within the mn after IHS are dependent on an intact vagus nerve. The excitation of neurons in the AP after IHS is partially dependent on vagal afferents, and the residual labeling that is present in the AP of neurectomized animals may be mediated via a blood-borne route.

Δ9-Tetrahydrocannabinol selectively acts on CB1 receptors in specific regions of dorsal vagal complex to inhibit emesis in ferrets

2003 ◽  
Vol 285 (3) ◽  
pp. G566-G576 ◽  
Author(s):  
Marja D. Van Sickle ◽  
Lorraine D. Oland ◽  
Ken Mackie ◽  
Joseph S. Davison ◽  
Keith A. Sharkey
Keyword(s):  
Receptor Antagonist ◽  
Brain Stem ◽  
Area Postrema ◽  
Motor Nucleus ◽  
Cb1 Receptors ◽  
Dorsal Vagal Complex ◽  
Dorsal Motor Nucleus ◽  
Site Of Action ◽  
Fos Expression ◽  
The Brain

The aim of this study was to investigate the efficacy, receptor specificity, and site of action of Δ9-tetrahydrocannabinol (THC) as an antiemetic in the ferret. THC (0.05-1 mg/kg ip) dose-dependently inhibited the emetic actions of cisplatin. The ED50 for retching was ∼0.1 mg/kg and for vomiting was 0.05 mg/kg. A specific cannabinoid (CB)1 receptor antagonist SR-141716A (5 mg/kg ip) reversed the effect of THC, whereas the CB2 receptor antagonist SR-144528 (5 mg/kg ip) was ineffective. THC applied to the surface of the brain stem was sufficient to inhibit emesis induced by intragastric hypertonic saline. The site of action of THC in the brain stem was further assessed using Fos immunohistochemistry. Fos expression induced by cisplatin in the dorsal motor nucleus of the vagus (DMNX) and the medial subnucleus of the nucleus of the solitary tract (NTS), but not other subnuclei of the NTS, was significantly reduced by THC rostral to obex. At the level of the obex, THC reduced Fos expression in the area postrema and the dorsal subnucleus of the NTS. The highest density of CB1 receptor immunoreactivity was found in the DMNX and the medial subnucleus of the NTS. Lower densities were observed in the area postrema and dorsal subnucleus of the NTS. Caudal to obex, there was moderate density of staining in the commissural subnucleus of the NTS. These results show that THC selectively acts at CB1 receptors to reduce neuronal activation in response to emetic stimuli in specific regions of the dorsal vagal complex.

Vestibular-mediated increase in central serotonin plays an important role in hypergravity-induced hypophagia in rats

2010 ◽  
Vol 109 (6) ◽  
pp. 1635-1643 ◽  
Author(s):  
Chikara Abe ◽  
Kunihiko Tanaka ◽  
Chihiro Iwata ◽  
Hironobu Morita
Keyword(s):  
Area Postrema ◽  
Vestibular Nucleus ◽  
Central Nucleus ◽  
Medial Vestibular Nucleus ◽  
Hypothalamic Nucleus ◽  
Solitary Tract ◽  
Afferent Pathway ◽  
Vestibular Input ◽  
Paraventricular Hypothalamic Nucleus ◽  
Fos Expression

Exposure to a hypergravity environment induces acute transient hypophagia, which is partially restored by a vestibular lesion (VL), suggesting that the vestibular system is involved in the afferent pathway of hypergravity-induced hypophagia. When rats were placed in a 3-G environment for 14 days, Fos-containing cells increased in the paraventricular hypothalamic nucleus, the central nucleus of the amygdala, the medial vestibular nucleus, the raphe nucleus, the nucleus of the solitary tract, and the area postrema. The increase in Fos expression was completely abolished or significantly suppressed by VL. Therefore, these regions may be critical for the initiation and integration of hypophagia. Because the vestibular nucleus contains serotonergic neurons and because serotonin (5-HT) is a key neurotransmitter in hypophagia, with possible involvement in motion sickness, we hypothesized that central 5-HT increases during hypergravity and induces hypophagia. To examine this proposition, the 5-HT concentrations in the cerebrospinal fluid were measured when rats were reared in a 3-G environment for 14 days. The 5-HT concentrations increased in the hypergravity environment, and these increases were completely abolished in rats with VL. Furthermore, a 5-HT2A antagonist (ketanserin) significantly reduced 3-G (120 min) load-induced Fos expression in the medial vestibular nucleus, and chronically administered ketanserin ameliorated hypergravity-induced hypophagia. These results indicate that hypergravity induces an increase in central 5-HT via the vestibular input and that this increase plays a significant role in hypergravity-induced hypophagia. The 5-HT2A receptor is involved in the signal transduction of hypergravity stress in the vestibular nucleus.

Localization of renin expressing cells in the brain, by use of a REN-eGFP transgenic model

2004 ◽  
Vol 16 (2) ◽  
pp. 240-246 ◽  
Author(s):  
Julie L. Lavoie ◽  
Martin D. Cassell ◽  
Kenneth W. Gross ◽  
Curt D. Sigmund
Keyword(s):  
Detection Threshold ◽  
Green Fluorescence Protein ◽  
Renin Angiotensin System ◽  
Central Nucleus ◽  
Ventrolateral Medulla ◽  
Motor Nucleus ◽  
Inferior Olivary Nucleus ◽  
Bed Nucleus ◽  
Lateral Parabrachial Nucleus ◽  
The Brain

Immunoreactive renin has been reported in the hypothalamus and cerebellar cortex in the rodent brain and in neurons in all areas of the human brain. Despite these observations and the clear documentation of the expression of the other renin-angiotensin system genes in the brain, the notion that renin is endogenously expressed in the brain remains very controversial and undefined. This controversy no doubt arises because the level of renin expression in the brain is below the detection threshold of most standard assays. A transgenic mouse expressing enhanced green fluorescence protein (eGFP) under the control of the mouse renin promoter was recently reported. This model expresses eGFP in the kidney, which responds appropriately to both developmental and physiological stimuli. We therefore used eGFP as a sensitive marker to identify renin-expressing cells in the brain. We identified eGFP-containing cells in specific areas of the brain, including cerebellum, hippocampus, dorsal motor nucleus of the vagus, inferior olivary nucleus, reticular formation, rostral ventrolateral medulla, central nucleus of the amygdala, lateral parabrachial nucleus, mesencephalic trigeminal nucleus, bed nucleus of stria terminalis, and subfornical organ. By colabeling with neuron- or glia (astrocytes or oligodendrocytes)-specific antisera, we have determined the eGFP-positive cells to be mainly neuronal. These findings therefore strongly support the primary expression of renin mRNA in the brain in regions controlling cardiovascular function.

scholarly journals Eff ect of a single asenapine treatment on Fos expression in the brain catecholamine-synthesizing neurons: impact of a chronic mild stress preconditioning

2017 ◽  
Vol 51 (2) ◽  
pp. 73-83
Author(s):  
J. Osacka ◽  
L. Horvathova ◽  
Z. Majercikova ◽  
Alexander Kiss
Keyword(s):  
Area Postrema ◽  
Chronic Mild Stress ◽  
Brain Structures ◽  
Ventrolateral Medulla ◽  
Mild Stress ◽  
Fos Protein ◽  
Male Wistar Rats ◽  
Fos Expression ◽  
Central Gray ◽  
The Brain

AbstractObjective. Fos protein expression in catecholamine-synthesizing neurons of the substantia nigra (SN) pars compacta (SNC, A8), pars reticulata (SNR, A9), and pars lateralis (SNL), the ventral tegmental area (VTA, A10), the locus coeruleus (LC, A6) and subcoeruleus (sLC), the ventrolateral pons (PON-A5), the nucleus of the solitary tract (NTS-A2), the area postrema (AP), and the ventrolateral medulla (VLM-A1) was quantitatively evaluated aft er a single administration of asenapine (ASE) (designated for schizophrenia treatment) in male Wistar rats preconditioned with a chronic unpredictable variable mild stress (CMS) for 21 days. Th e aim of the present study was to reveal whether a single ASE treatment may 1) activate Fos expression in the brain areas selected; 2) activate tyrosine hydroxylase (TH)-synthesizing cells displaying Fos presence; and 3) be modulated by CMS preconditioning.Methods. Control (CON), ASE, CMS, and CMS+ASE groups were used. CMS included restraint, social isolation, crowding, swimming, and cold. Th e ASE and CMS+ASE groups received a single dose of ASE (0.3 mg/kg, s.c.) and CON and CMS saline (300 μl/rat, s.c.). The animals were sacrificed 90 min aft er the treatments. Fos protein and TH-labeled immunoreactive perikarya were analyzed on double labeled histological sections and enumerated on captured pictures using combined light and fluorescence microscope illumination.Results. Saline or CMS alone did not promote Fos expression in any of the structures investigated. ASE alone or in combination with CMS elicited Fos expression in two parts of the SN (SNC, SNR) and the VTA. Aside from some cells in the central gray tegmental nuclei adjacent to LC, where a small number of Fos profiles occurred, none or negligible Fos occurrence was detected in the other structures investigated including the LC and sLC, PON-A5, NTS-A2, AP, and VLM-A1. CMS preconditioning did not infl uence the level of Fos induction in the SN and VTA elicited by ASE administration. Similarly, the ratio between the amount of free Fos and Fos colocalized with TH was not aff ected by stress preconditioning in the SNC, SNR, and the VTA.Conclusions. Th e present study provides an anatomical/functional knowledge about the nature of the acute ASE treatment on the catecholamine-synthesizing neurons activity in certain brain structures and their missing interplay with the CMS preconditioning.

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