The anorectic hormone amylin contributes to feeding-related changes of neuronal activity in key structures of the gut-brain axis

2004 ◽  
Vol 286 (1) ◽  
pp. R114-R122 ◽  
Author(s):  
T. Riediger ◽  
D. Zuend ◽  
C. Becskei ◽  
T. A. Lutz
Keyword(s):  
Food Intake ◽  
Area Postrema ◽  
Peptide Hormone ◽  
Central Nucleus ◽  
Circumventricular Organ ◽  
Hypothalamic Area ◽  
Physiological Concentration ◽  
Lateral Parabrachial Nucleus ◽  
Neuronal Mechanisms ◽  
Fos Expression

Amylin is a peptide hormone that is cosecreted with insulin from the pancreas during and after food intake. Peripherally injected amylin potently inhibits feeding by acting on the area postrema (AP), a circumventricular organ lacking a functional blood-brain barrier. We recently demonstrated that AP neurons are excited by a near physiological concentration of amylin. However, the subsequent neuronal mechanisms and the relevance of endogenously released amylin for the regulation of food intake are poorly understood. Therefore, we investigated 1) amylin's contribution to feeding-induced c-Fos expression in the rat AP and its ascending projection sites, and 2) amylin's ability to reverse fasting-induced c-Fos expression in the lateral hypothalamic area (LHA). Similar to amylin (20 μg/kg sc), refeeding of 24-h food-deprived rats induced c-Fos expression in the AP, the nucleus of the solitary tract, the lateral parabrachial nucleus, and the central nucleus of the amygdala. In AP-lesioned rats, the amylin-induced c-Fos expression in each of these sites was blunted, indicating an AP-mediated activation of these structures. Pretreatment with the amylin antagonist AC-187 (1 mg/kg sc) inhibited feeding-induced c-Fos expression in the AP. Food deprivation activated LHA neurons, a response known to be associated with hunger. This effect was reversed within 2 h after refeeding and also in nonrefed animals that received amylin. In summary, our data provide the first evidence that feeding-induced amylin release activates AP neurons projecting to subsequent relay stations known to transmit meal-related signals to the forebrain. Activation of this pathway seems to coincide with an inhibition of LHA neurons.

Estradiol treatment increases CCK-induced c-Fos expression in the brains of ovariectomized rats

2002 ◽  
Vol 283 (6) ◽  
pp. R1378-R1385 ◽  
Author(s):  
Lisa A. Eckel ◽  
Thomas A. Houpt ◽  
Nori Geary
Keyword(s):  
Food Intake ◽  
Area Postrema ◽  
Body Weight Gain ◽  
Meal Size ◽  
Female Rats ◽  
Central Nucleus ◽  
Ovariectomized Rats ◽  
Estradiol Treatment ◽  
Central Processing ◽  
Fos Expression

The ovarian hormone estradiol reduces meal size and food intake in female rats, at least in part by increasing the satiating potency of CCK. Here we used c-Fos immunohistochemistry to determine whether estradiol increases CCK-induced neuronal activation in several brain regions implicated in the control of feeding. Because the adiposity signals leptin and insulin appear to control feeding in part by increasing the satiating potency of CCK, we also examined whether increased adiposity after ovariectomy influences estradiol's effects on CCK-induced c-Fos expression. Ovariectomized rats were injected subcutaneously with 10 μg 17β-estradiol benzoate (estradiol) or vehicle once each on Monday and Tuesday for 1 wk ( experiment 1) or for 5 wk ( experiment 2). Two days after the final injection of estradiol or vehicle, rats were injected intraperitoneally with 4 μg/kg CCK in 1 ml/kg 0.9 M NaCl or with vehicle alone. Rats were perfused 60 min later, and brain tissue was collected and processed for c-Fos immunoreactivity. CCK induced c-Fos expression in the nucleus of the solitary tract (NTS), area postrema (AP), paraventricular nucleus of the hypothalamus (PVN), and central nucleus of the amygdala (CeA) in vehicle- and estradiol-treated ovariectomized rats. Estradiol treatment further increased this response in the caudal, subpostremal, and intermediate NTS, the PVN, and the CeA, but not in the rostral NTS or AP. This action of estradiol was very similar in rats tested before ( experiment 1) and after ( experiment 2) significant body weight gain, suggesting that adiposity does not modulate CCK-induced c-Fos expression or interact with estradiol's ability to modulate CCK-induced c-Fos expression. These findings suggest that estradiol inhibits meal size and food intake by increasing the central processing of the vagal CCK satiation signal.

Duodenal loading with glucose induces Fos expression in rat brain: selective blockade by devazepide

1999 ◽  
Vol 277 (3) ◽  
pp. R667-R674 ◽  
Author(s):  
Lixin Wang ◽  
Sylvain Cardin ◽  
Vicente Martínez ◽  
Yvette Taché ◽  
K. C. Kent Lloyd
Keyword(s):  
Area Postrema ◽  
Central Nucleus ◽  
Intestinal Lumen ◽  
Sprague Dawley ◽  
Selective Blockade ◽  
Lateral Parabrachial Nucleus ◽  
Sprague Dawley Rats ◽  
Fos Expression ◽  
The Brain

The role of CCK in mediating neuronal activity in the brain in response to dietary carbohydrate was measured by detecting Fos immunoreactivity in response to duodenal glucose load in rats after administration of the CCK-A receptor antagonist devazepide. In adult, male Sprague-Dawley rats, infusion for 30 min of 545 mg (2.18 kcal) dextrose through a duodenal cannula induced Fos expression in the nucleus of the solitary tract (NTS), area postrema (AP), lateral division of the central nucleus of the amygdala (CeAL), and the external subnucleus of the lateral parabrachial nucleus (LPBE). Devazepide treatment (1 mg/kg) attenuated Fos expression in the NTS and AP by 81 and 78%, respectively, but not in the CeAL or LPBE. These results indicate that central neuronal activation is elicited by dietary glucose in the intestinal lumen and that activation of neurons in the NTS and AP is mediated by CCK-A receptors.

Diet-Derived Nutrients Modulate the Effects of Amylin on c-Fos Expression in the Area Postrema and on Food Intake

2007 ◽  
Vol 86 (2) ◽  
pp. 124-135 ◽  
Author(s):  
Signe Michel ◽  
Csilla Becskei ◽  
Elif Erguven ◽  
Thomas A. Lutz ◽  
Thomas Riediger
Keyword(s):  
Food Intake ◽  
Area Postrema ◽  
Fos Expression

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.

Lesions of area postrema attenuate but do not prevent anorectic action of peripheral serotonin in rats

1995 ◽  
Vol 269 (6) ◽  
pp. R1314-R1320 ◽  
Author(s):  
V. Adipudi ◽  
K. J. Simansky
Keyword(s):  
Food Intake ◽  
Dose Response ◽  
Area Postrema ◽  
Behavioral Analysis ◽  
High Dose ◽  
Reduce Food Intake ◽  
Circumventricular Organ ◽  
Behavioral Toxicity ◽  
Dose Dependent ◽  
Dose Response Function

These studies assessed the effect of selectively ablating the area postrema (AP) on the action of peripheral serotonin [5-hydroxytryptamine (5-HT)] to reduce food intake in rats. Intraperitoneal 5-HT (0, 2.0, 4.0, and 8.0 mumol/kg) reduced the intakes of sweetened mash during a 30-min test in controls (APC) and in AP-lesioned rats (APX). The anorexia was dose dependent in controls but the dose-response function was flat after AP lesions. In another study, 2.0 mumol/kg 5-HT reduced intakes of both groups by approximately 25%, but AP lesions blunted the effect at 8.0 mumol/kg 5-HT (APX, -30% vs. APC, -85%). Behavioral analysis revealed that, compared with controls, AP lesions eliminated the decrease in frequency of feeding and reduced the incidence of resting and of an aberrant posture observed after 8.0 mumol/kg. Thus peripheral 5-HT decreases food intake in rats with AP lesions. Multiple mechanisms appear to be involved in the ability of peripheral 5-HT to reduce feeding. A high dose of 5-HT promotes responses associated with satiation but also produces behavioral toxicity; these effects involve the AP. Lower doses appear to engage processes that do not rely on the function of this circumventricular organ.

Nutrients modulate amylin's effect on c-Fos expression in the area postrema and on food intake.

Appetite ◽  
2007 ◽  
Vol 49 (1) ◽  
pp. 314
Author(s):  
S. Michel ◽  
T. Lutz ◽  
T. Riediger
Keyword(s):  
Food Intake ◽  
Area Postrema ◽  
Fos Expression

Progressive postnatal increases in Fos immunoreactivity in the forebrain and brain stem of rats after viscerosensory stimulation with lithium chloride

2007 ◽  
Vol 292 (3) ◽  
pp. R1212-R1223 ◽  
Author(s):  
Thomas J. Koehnle ◽  
Linda Rinaman
Keyword(s):  
Lithium Chloride ◽  
Area Postrema ◽  
Central Nucleus ◽  
Neural Activation ◽  
Activation Patterns ◽  
Bed Nucleus ◽  
Rat Pups ◽  
Fos Protein ◽  
Functional Development ◽  
Lateral Parabrachial Nucleus

Interoceptive signals have a powerful impact on the motivation and emotional learning of animals during stressful experiences. However, current insights into the organization of interoceptive pathways stem mainly from observation and manipulation of adults, and little is known regarding the functional development of viscerosensory signaling pathways. To address this, we have examined central neural activation patterns in rat pups after treatment with lithium chloride (LiCl), a malaise-inducing agent. Rat pups were injected intraperitoneally with 0.15 M LiCl or 0.15 M NaCl (2% body wt) on postnatal day (P)0, 7, 14, 21, or 28, perfused 60 to 90 min postinjection, and their brains assayed for Fos protein immunolabeling. Compared with saline treatment, LiCl increased Fos only slightly in the area postrema, nucleus of the solitary tract, and lateral parabrachial nucleus on P0. LiCl did not increase Fos above control levels in the central nucleus of the amygdala, bed nucleus of the stria terminalis (BNST), or paraventricular nucleus of the hypothalamus on P0 but did on P7 and later. Maximal Fos responses to LiCl were observed on P14 in all areas except the BNST, in which LiCl-induced Fos activation continued to increase through P28. These results indicate that central LiCl-sensitive interoceptive circuits in rats are not fully functional at birth, and show age-dependent increases in neural Fos responses to viscerosensory stimulation with LiCl.

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.

The area postrema modulates hypothalamic Fos responses to intragastric hypertonic saline in conscious rats

1998 ◽  
Vol 275 (6) ◽  
pp. R1921-R1927 ◽  
Author(s):  
Scott H. Carlson ◽  
John P. Collister ◽  
John W. Osborn
Keyword(s):  
Hypertonic Saline ◽  
Sham Group ◽  
Area Postrema ◽  
Conscious Rats ◽  
Afferent Projections ◽  
Lateral Parabrachial Nucleus ◽  
Sodium Load ◽  
Efferent Projections ◽  
Fos Expression ◽  
Hypertonic Saline Infusion

We have recently reported that an acute intragastric hypertonic saline load increases Fos immunoreactivity in several central nuclei, including the supraoptic nucleus (SON), paraventricular nucleus (PVN), nucleus of the solitary tract (NTS), area postrema (AP), and lateral parabrachial nucleus (LPBN). We have also shown that these responses are mediated by stimulation of peripheral osmoreceptors with splanchnic and vagal afferent projections. However, it is unclear whether the primary projections of peripheral osmoreceptors terminate in the NTS or the AP, both of which project to the SON and PVN. This study tested the hypothesis that efferent projections from the AP were necessary for the Fos responses in the SON, PVN, and LPBN. We examined the effect of AP lesion on the response of central Fos immunoreactivity to intragastric hypertonic saline infusion in conscious rats. Compared with sham-lesioned rats ( n = 5), Fos expression in AP-lesioned rats ( n = 6) was similar in the SON following the intragastric sodium load. However, in contrast to the sham group, Fos expression was significantly reduced in the PVN of AP-lesioned rats. Fos levels observed in the NTS and LPBN were similar in both groups. These results suggest that the PVN response to intragastric hypertonic saline is dependent on efferent projections from the AP. In contrast, Fos responses to this stimulus in the NTS, SON, and LPBN are independent of the activity of the AP.

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