Lesions of area postrema and subfornical organ alter exendin-4-induced brain activation without preventing the hypophagic effect of the GLP-1 receptor agonist

2010 ◽  
Vol 298 (4) ◽  
pp. R1098-R1110 ◽  
Author(s):  
Elena-Dana Baraboi ◽  
Pauline Smith ◽  
Alastair V. Ferguson ◽  
Denis Richard
Keyword(s):  
Area Postrema ◽  
Brain Structures ◽  
Circumventricular Organs ◽  
Primary Objective ◽  
Subfornical Organ ◽  
Metabolic Effects ◽  
Ventrolateral Medulla ◽  
Hypothalamic Nucleus ◽  
Medial Nucleus ◽  
Electrolytic Ablation

The mechanism and route whereby glucagon-like peptide 1 (GLP-1) receptor agonists, such as GLP-1 and exendin-4 (Ex-4), access the central nervous system (CNS) to exert their metabolic effects have yet to be clarified. The primary objective of the present study was to investigate the potential role of two circumventricular organs (CVOs), the area postrema (AP) and the subfornical organ (SFO), in mediating the metabolic and CNS-stimulating effects of Ex-4. We demonstrated that electrolytic ablation of the AP, SFO, or AP + SFO does not acutely prevent the anorectic effects of Ex-4. AP + SFO lesion chronically decreased food intake and body weight and also modulated the effect of Ex-4 on the neuronal activation of brain structures involved in the hypothalamic-pituitary-adrenal axis and glucose metabolism. The results of the study also showed that CVO lesions blunted Ex-4-induced expression of c- fos mRNA (a widely used neuronal activity marker) in 1) limbic structures (bed nucleus of the stria terminalis and central amygdala), 2) hypothalamus (paraventricular hypothalamic nucleus, supraoptic nucleus, and arcuate nucleus), and 3) hindbrain (lateral and lateral-external parabrachial nucleus, medial nucleus of the solitary tract, and ventrolateral medulla). In conclusion, although the present results do not support a role for the CVOs in the anorectic effect induced by a single injection of Ex-4, they suggest that the CVOs play important roles in mediating the actions of Ex-4 in the activation of CNS structures involved in homeostatic control.

Central actions of angiotensin in cardiovascular control: Multiple roles for a single peptide

1992 ◽  
Vol 70 (5) ◽  
pp. 779-785 ◽  
Author(s):  
Alastair V. Ferguson ◽  
Katharine M. Wall
Keyword(s):  
Blood Pressure ◽  
Area Postrema ◽  
Circumventricular Organs ◽  
Subfornical Organ ◽  
Cardiovascular Control ◽  
Multiple Roles ◽  
Ang Ii ◽  
Electrophysiological Studies ◽  
The Central Nervous System ◽  
Central Actions

Angiotensin II (ANG II) acts peripherally as a hormone, with actions on the vasculature, adrenals, and kidney. In addition, certain actions of ANG II in the central nervous system are directed toward cardiovascular control and fluid volume homeostasis. Dense binding sites for ANG II are found at circumventricular organs, which apparently have the ability to relay information to cardiovascular centers via neural circuitry. Microinjection of ANG II into the subfornical organ (SFO) or area postrema (AP) produces site-specific increases in blood pressure. In addition, electrophysiological studies demonstrate profound effects of ANG II, acting at the SFO, on activity of neurohypophysial neurons and release of oxytocin and vasopressin, which can be antagonized by ANG II blockers or attenuated by SFO lesions. Evidence from microinjection, electrophysiological, and lesion studies indicate a complex interaction between central sites involved in mechanisms of cardiovascular control: the SFO, AP, organum vasculosum of the lamina terminalis, and paraventricular and supraoptic nuclei of the hypothalamus. Not only is ANG II a humoral messenger in this central scenario, but evidence suggests it acts as a neurotransmitter or neuroendocrine substance within specific CNS pathways, suggesting multiple roles for this peptide in central cardiovascular control.Key words: blood pressure regulation, circumventricular organs, vasopressin, area postrema, subfornical organ.

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 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.

scholarly journals Beta-catenin signaling regulates barrier-specific gene expression in circumventricular organ and ocular vasculatures

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Yanshu Wang ◽  
Mark F Sabbagh ◽  
Xiaowu Gu ◽  
Amir Rattner ◽  
John Williams ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Area Postrema ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Brain Structures ◽  
Circumventricular Organs ◽  
Specific Gene ◽  
Beta Catenin ◽  
High Permeability ◽  
Wnt Inhibitory Factor 1

The brain, spinal cord, and retina are supplied by capillaries that do not permit free diffusion of molecules between serum and parenchyma, a property that defines the blood-brain and blood-retina barriers. Exceptions to this pattern are found in circumventricular organs (CVOs), small midline brain structures that are supplied by high permeability capillaries. In the eye and brain, high permeability capillaries are also present in the choriocapillaris, which supplies the retinal pigment epithelium and photoreceptors, and the ciliary body and choroid plexus, the sources of aqueous humor and cerebrospinal fluid, respectively. We show here that (1) endothelial cells in these high permeability vascular systems have very low beta-catenin signaling compared to barrier-competent endothelial cells, and (2) elevating beta-catenin signaling leads to a partial conversion of permeable endothelial cells to a barrier-type state. In one CVO, the area postrema, high permeability is maintained, in part, by local production of Wnt inhibitory factor-1.

Circumventricular organs and fever

1997 ◽  
Vol 273 (5) ◽  
pp. R1690-R1695 ◽  
Author(s):  
Yoshimi Takahashi ◽  
Pauline Smith ◽  
Alistair Ferguson ◽  
Quentin J. Pittman
Keyword(s):  
Body Temperature ◽  
Area Postrema ◽  
Circumventricular Organs ◽  
Subfornical Organ ◽  
Prostaglandin E ◽  
Lamina Terminalis ◽  
Sham Control ◽  
Access Points ◽  
Efferent Projections ◽  
Intravenous Catheters

We have examined the roles of three circumventricular organs, the area postrema, the subfornical organ, and the organum vasculosum of the lamina terminalis (OVLT), as possible access points for circulating pyrogens to cause fever. In conscious, unrestrained rats prepared with telemetry devices, intracerebroventricular cannulas, and intravenous catheters, body temperature was monitored after intravenously administered lipopolysaccharide and, on a different occasion, after intracerebroventricular prostaglandin E1. Lipopolysaccharide-induced fevers in sham control lesioned rats were indistinguishable from those observed in animals with lesions of the area postrema, the OVLT, or the tissue immediately adjacent to this structure (peri-OVLT). In contrast, rats with lesions of the subfornical organ displayed reduced fevers. In none of the groups of lesioned animals were prostaglandin E1 fevers reduced. Thus lesions did not interfere with central thermogenic pathways responsive to prostaglandin. Our results indicate that subfornical organ neurons respond to circulating pyrogens and through their efferent projections activate central pathways involved in fever.

Alterations in atrial natriuretic peptide receptors in rat brain nuclei during hypertension and dehydration

1988 ◽  
Vol 66 (3) ◽  
pp. 288-294 ◽  
Author(s):  
Juan M. Saavedra
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Rat Brain ◽  
Choroid Plexus ◽  
Natriuretic Peptide ◽  
Area Postrema ◽  
Circumventricular Organs ◽  
Subfornical Organ ◽  
Peptide Receptors ◽  
Natriuretic Peptide Receptors ◽  
Atrial Natriuretic

We have studied the localization, kinetics, and regulation of receptors for the circulating form of the atrial natriuretic peptide (99–126) in the rat brain. Atrial natriuretic peptide receptors were discretely localized in the rat brain, with the highest concentrations in circumventricular organs, the choroid plexus, and selected hypothalamic nuclei involved in the production of the antidiuretic hormone vasopressin and in blood pressure control. Spontaneously (genetic) hypertensive rats showed much lower numbers of atrial natriuretic peptide receptors than normotensive controls in the subfornical organ, the area postrema, the nucleus of the solitary tract, and in the choroid plexus. These changes are in contrast with those observed for receptors of angiotensin II, another circulating peptide with actions opposite to those of the atrial natriuretic peptide. In acute dehydration after water deprivation, as well as in chronic dehydration such as that present in homozygous Brattleboro rats, there was an up-regulation of atrial natriuretic peptide receptors in the subfornical organ. Thus, circumventricular organs contain atrial natriuretic peptide receptors that could respond to variations in the concentration of circulating peptide. The localization of atrial natriuretic peptide receptors and the alterations in their regulation present in hypertensive and dehydrated rats indicate that these brain receptors are related to fluid regulation, including the secretion of vasopressin, and to cardiovascular function. Atrial natriuretic peptide receptors in the choroid plexus may be related to the formation of cerebrospinal fluid.

scholarly journals Adjustment of Whey:Casein Ratio from 20:80 to 60:40 in Milk Formulation Affects Food Intake and Brainstem and Hypothalamic Neuronal Activation and Gene Expression in Laboratory Mice

Foods ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 658
Author(s):  
Erin L. Wood ◽  
David G. Christian ◽  
Mohammed Arafat ◽  
Laura K. McColl ◽  
Colin G. Prosser ◽  
...  
Keyword(s):  
Food Intake ◽  
Area Postrema ◽  
Energy Levels ◽  
Early Gene ◽  
Hypothalamic Nucleus ◽  
Laboratory Mice ◽  
Neuronal Activation ◽  
Short Term ◽  
Animal Milk ◽  
The Impact

Adjustment of protein content in milk formulations modifies protein and energy levels, ensures amino acid intake and affects satiety. The shift from the natural whey:casein ratio of ~20:80 in animal milk is oftentimes done to reflect the 60:40 ratio of human milk. Studies show that 20:80 versus 60:40 whey:casein milks differently affect glucose metabolism and hormone release; these data parallel animal model findings. It is unknown whether the adjustment from the 20:80 to 60:40 ratio affects appetite and brain processes related to food intake. In this set of studies, we focused on the impact of the 20:80 vs. 60:40 whey:casein content in milk on food intake and feeding-related brain processes in the adult organism. By utilising laboratory mice, we found that the 20:80 whey:casein milk formulation was consumed less avidly and was less preferred than the 60:40 formulation in short-term choice and no-choice feeding paradigms. The relative PCR analyses in the hypothalamus and brain stem revealed that the 20:80 whey:casein milk intake upregulated genes involved in early termination of feeding and in an interplay between reward and satiety, such as melanocortin 3 receptor (MC3R), oxytocin (OXT), proopiomelanocortin (POMC) and glucagon-like peptide-1 receptor (GLP1R). The 20:80 versus 60:40 whey:casein formulation intake differently affected brain neuronal activation (assessed through c-Fos, an immediate-early gene product) in the nucleus of the solitary tract, area postrema, ventromedial hypothalamic nucleus and supraoptic nucleus. We conclude that the shift from the 20:80 to 60:40 whey:casein ratio in milk affects short-term feeding and relevant brain processes.

Fluorescein-Enhanced Characterization of Additional Anatomical Landmarks in Cerebral Ventricular Endoscopy

Neurosurgery ◽  
2013 ◽  
Vol 72 (5) ◽  
pp. 855-860 ◽  
Author(s):  
Pierluigi Longatti ◽  
Luca Basaldella ◽  
Francesco Sammartino ◽  
Alessandro Boaro ◽  
Alessandro Fiorindi
Keyword(s):  
Choroid Plexus ◽  
White Light ◽  
Area Postrema ◽  
Functional Anatomy ◽  
Circumventricular Organs ◽  
Third Ventriculostomy ◽  
Cancer Tissue ◽  
Anatomical Landmarks ◽  
Fluorescein Sodium ◽  
Anatomic Landmarks

Abstract BACKGROUND: Fluorescein enhancement to detect retinal disorder or differentiate cancer tissue in situ is a well-defined diagnostic procedure. It is a visible marker of where the blood-brain barrier is absent or disrupted. Little is reported in the contemporary literature on endoscopic fluorescein-enhanced visualization of the circumventricular organs, and the relevance of these structures as additional markers for safe ventricular endoscopic navigation remains an unexplored field. OBJECTIVE: To describe fluorescein sodium–enhanced visualization of circumventricular organs as additional anatomic landmarks during endoscopic ventricular surgery procedures. METHODS: We prospectively administered intravenously 500 mg fluorescein sodium in 12 consecutive endoscopic surgery patients. A flexible endoscope equipped with dual observation modes for both white light and fluorescence was used. During navigation from the lateral to the fourth ventricle, the endoscopic anatomic landmarks were first inspected under white light and then under the fluorescent mode. RESULTS: After a mean of 20 seconds in the fluorescent mode, the fluorescein enhanced visualization of the choroid plexus of the lateral ventricle, median eminence–tuber cinereum complex, organum vasculosum of the lamina terminalis, choroid plexus of the third and fourth ventricles, and area postrema. CONCLUSION: Fluorescein-enhanced visualization is a useful tool for helping neuroendoscopists recognize endoscopic anatomic landmarks. It could be adopted to guide orientation when the surgeon deems an endoscopic procedure unsafe or contraindicated because of unclear or subverted anatomic landmarks. Visualization of the circumventricular organs could add new insight into the functional anatomy of these structures, with possible implications for the site and safety of third ventriculostomy.

scholarly journals Effect of sex chromosome complement on sodium appetite and Fos-immunoreactivity induced by sodium depletion

2014 ◽  
Vol 306 (3) ◽  
pp. R175-R184 ◽  
Author(s):  
Florencia M. Dadam ◽  
Ximena E. Caeiro ◽  
Carla D. Cisternas ◽  
Ana F. Macchione ◽  
María J. Cambiasso ◽  
...  
Keyword(s):  
Sex Chromosome ◽  
Area Postrema ◽  
Brain Activity ◽  
Chromosome Complement ◽  
Circumventricular Organs ◽  
Sexually Dimorphic ◽  
Sodium Depletion ◽  
Sodium Diet ◽  
Sodium Appetite ◽  
Low Sodium Diet

Previous studies indicate a sex chromosome complement (SCC) effect on the angiotensin II-sexually dimorphic hypertensive and bradycardic baroreflex responses. We sought to evaluate whether SCC may differentially modulate sexually dimorphic-induced sodium appetite and specific brain activity due to physiological stimulation of the rennin angiotensin system. For this purpose, we used the “four core genotype” mouse model, in which the effect of gonadal sex and SCC is dissociated, allowing comparisons of sexually dimorphic traits between XX and XY females as well as in XX and XY males. Gonadectomized mice were sodium depleted by furosemide (50 mg/kg) and low-sodium diet treatment; control groups were administered with vehicle and maintained on normal sodium diet. Twenty-one hours later, the mice were divided into two groups: one group was submitted to the water-2% NaCl choice intake test, while the other group was perfused and their brains subjected to the Fos-immunoreactivity (FOS-ir) procedure. Sodium depletion, regardless of SCC (XX or XY), induced a significantly lower sodium and water intake in females than in males, confirming the existence in mice of sexual dimorphism in sodium appetite and the organizational involvement of gonadal steroids. Moreover, our results demonstrate a SCC effect on induced brain FOS-ir, showing increased brain activity in XX-SCC mice at the paraventricular nucleus, nucleus of the solitary tract, and lateral parabrachial nucleus, as well as an XX-SCC augmented effect on sodium depletion-induced brain activity at two circumventricular organs, the subfornical organ and area postrema, nuclei closely involved in fluid and blood pressure homeostasis.

Sign in / Sign up

Export Citation Format

Share Document