scholarly journals Regulation of food intake by astrocytes in the brainstem dorsal vagal complex

2019 ◽  
Author(s):  
Alastair J. MacDonald ◽  
Fiona E. Holmes ◽  
Craig Beall ◽  
Anthony E. Pickering ◽  
Kate L.J. Ellacott
Keyword(s):  
Food Intake ◽  
Area Postrema ◽  
Active Role ◽  
Brain Regions ◽  
Negative Energy ◽  
Motor Nucleus ◽  
Dorsal Vagal Complex ◽  
Structural Support ◽  
Dorsal Motor Nucleus ◽  
Hypothalamic Arcuate Nucleus

Food intake is controlled by the coordinated action of numerous brain regions but a complete understanding remains elusive. Of these brain regions the brainstem dorsal vagal complex (DVC) is the first site for integration of visceral synaptic and hormonal cues that act to inhibit food intake. The DVC consists of three nuclei: the nucleus of the solitary tract (NTS), area postrema (AP) and dorsal motor nucleus of the vagus (DMX). Targeted chemogenetic activation of appetite-responsive NTS neuronal populations causes short term decreases in food intake. Astrocytes are a class of glial cell which provide metabolic and structural support to neurons and play an active role in modulating neurotransmission. Within the hypothalamic arcuate nucleus (ARC) astrocytes are regulated by both positive and negative energy balance and express receptors for hormones that influence satiety and hunger. Chemogenetic activation of these ARC astrocytes alters food intake. Since NTS astrocytes respond to vagal stimulation, we hypothesised that they may be involved in mediating satiety. Here we show that NTS astrocytes show plastic alterations in morphology following excess food consumption and that chemogenetic activation of DVC astrocytes causes a decrease in food intake, by recruiting an appetite-inhibiting circuit, without producing aversion. These findings are the first using genetically-targeted manipulation of DVC astrocytes to demonstrate their role in the brain’s regulation of food intake.

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.

scholarly journals Single-Cell Mapping of GLP-1 and GIP Receptor Expression in the Dorsal Vagal Complex

2021 ◽  
Author(s):  
Mette Q. Ludwig ◽  
Petar V. Todorov ◽  
Kristoffer L. Egerod ◽  
David P. Olson ◽  
Tune H. Pers
Keyword(s):  
Single Cell ◽  
Area Postrema ◽  
Critical Role ◽  
Receptor Expression ◽  
Motor Nucleus ◽  
Dorsal Vagal Complex ◽  
Dorsal Motor Nucleus ◽  
Glucagon Like Peptide 1 ◽  
Mapping Techniques ◽  
Gip Receptor

The dorsal vagal complex (DVC) in the hindbrain, composed of the area postrema, nucleus of the solitary tract and dorsal motor nucleus of the vagus, plays a critical role in modulating satiety. The incretins glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) act directly in the brain to modulate feeding, and receptors for both are expressed in the DVC. Given the impressive clinical responses to pharmacologic manipulation of incretin signaling, understanding the central mechanisms by which incretins alter metabolism and energy balance are of critical importance. Here, we review recent single-cell approaches used to detect molecular signatures of GLP-1 and GIP receptor-expressing cells in the DVC. In addition, we discuss how current advancements in single-cell transcriptomics, epigenetics, spatial transcriptomics, and circuit mapping techniques have the potential to further characterize incretin circuits in the hindbrain.

scholarly journals Single-Cell Mapping of GLP-1 and GIP Receptor Expression in the Dorsal Vagal Complex

2021 ◽  
Author(s):  
Mette Q. Ludwig ◽  
Petar V. Todorov ◽  
Kristoffer L. Egerod ◽  
David P. Olson ◽  
Tune H. Pers
Keyword(s):  
Single Cell ◽  
Area Postrema ◽  
Critical Role ◽  
Receptor Expression ◽  
Motor Nucleus ◽  
Dorsal Vagal Complex ◽  
Dorsal Motor Nucleus ◽  
Glucagon Like Peptide 1 ◽  
Mapping Techniques ◽  
Gip Receptor

The dorsal vagal complex (DVC) in the hindbrain, composed of the area postrema, nucleus of the solitary tract and dorsal motor nucleus of the vagus, plays a critical role in modulating satiety. The incretins glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) act directly in the brain to modulate feeding, and receptors for both are expressed in the DVC. Given the impressive clinical responses to pharmacologic manipulation of incretin signaling, understanding the central mechanisms by which incretins alter metabolism and energy balance are of critical importance. Here, we review recent single-cell approaches used to detect molecular signatures of GLP-1 and GIP receptor-expressing cells in the DVC. In addition, we discuss how current advancements in single-cell transcriptomics, epigenetics, spatial transcriptomics, and circuit mapping techniques have the potential to further characterize incretin circuits in the hindbrain.

scholarly journals Single-Cell Mapping of GLP-1 and GIP Receptor Expression in the Dorsal Vagal Complex

2021 ◽  
Author(s):  
Mette Q. Ludwig ◽  
Petar V. Todorov ◽  
Kristoffer L. Egerod ◽  
David P. Olson ◽  
Tune H. Pers
Keyword(s):  
Single Cell ◽  
Area Postrema ◽  
Critical Role ◽  
Receptor Expression ◽  
Motor Nucleus ◽  
Dorsal Vagal Complex ◽  
Dorsal Motor Nucleus ◽  
Glucagon Like Peptide 1 ◽  
Mapping Techniques ◽  
Gip Receptor

The dorsal vagal complex (DVC) in the hindbrain, composed of the area postrema, nucleus of the solitary tract and dorsal motor nucleus of the vagus, plays a critical role in modulating satiety. The incretins glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) act directly in the brain to modulate feeding, and receptors for both are expressed in the DVC. Given the impressive clinical responses to pharmacologic manipulation of incretin signaling, understanding the central mechanisms by which incretins alter metabolism and energy balance are of critical importance. Here, we review recent single-cell approaches used to detect molecular signatures of GLP-1 and GIP receptor-expressing cells in the DVC. In addition, we discuss how current advancements in single-cell transcriptomics, epigenetics, spatial transcriptomics, and circuit mapping techniques have the potential to further characterize incretin circuits in the hindbrain.

scholarly journals The Role of the Dorsal Vagal Complex and the Vagus Nerve in Feeding Effects of Melanocortin-3/4 Receptor Stimulation*

Endocrinology ◽  
2000 ◽  
Vol 141 (4) ◽  
pp. 1332-1337 ◽  
Author(s):  
Diana L. Williams ◽  
Joel M. Kaplan ◽  
Harvey J. Grill
Keyword(s):  
Food Intake ◽  
Vagus Nerve ◽  
Messenger Rna ◽  
Motor Nucleus ◽  
Dorsal Vagal Complex ◽  
Dorsal Motor Nucleus ◽  
Ventricular Response ◽  
Feeding Effects ◽  
Diet Intake

Abstract Fourth intracerebroventricular (4th-icv) administration of the melanocortin-3/4 receptor (MC3/4-R) agonist, MTII, reduces food intake; the antagonist, SHU9119, increases feeding. The dorsal motor nucleus of the vagus nerve (DMX) contains the highest density of MC4-R messenger RNA in the brain. To explore the possibility that the DMX contributes to 4th-icv MC4-R effects, we delivered doses of MTII and SHU9119 that are subthreshold for ventricular response unilaterally through a cannula centered above the DMX. MTII markedly suppressed 2-h (50%), 4-h (50%), and 24-h (33%) intake. Feeding was significantly increased 4 h (50%) and 24 h (20%) after SHU9119 injections. These results suggest that receptors in the DMX, or the dorsal vagal complex more generally, underlie effects obtained with 4th-icv administration of these ligands. We investigated possible vagal mediation of 4th-icv MTII effects by giving the agonist to rats with subdiaphragmatic vagotomy. MTII suppressed 2-, 4-, and 24-h liquid diet intake (∼80%) to the same extent in vagotomized and surgical control rats. We conclude that stimulation or antagonism of MC3/4-Rs in the dorsal vagal complex yields effects on food intake that do not require an intact vagus nerve.

scholarly journals Mapping of SARS-CoV-2 Brain Invasion and Histopathology in COVID-19 Disease

2021 ◽  
Author(s):  
Geidy E. Serrano ◽  
Jessica E. Walker ◽  
Richard Arce ◽  
Michael J. Glass ◽  
Daisy Vargas ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
Area Postrema ◽  
Brain Regions ◽  
Motor Nucleus ◽  
Brain Invasion ◽  
Dorsal Motor Nucleus ◽  
Age Related ◽  
The Subject ◽  
Human Coronaviruses ◽  
Acute Cerebral Infarct

ABSTRACTThe coronavirus SARS-CoV-2 (SCV2) causes acute respiratory distress, termed COVID-19 disease, with substantial morbidity and mortality. As SCV2 is related to previously-studied coronaviruses that have been shown to have the capability for brain invasion, it seems likely that SCV2 may be able to do so as well. To date, although there have been many clinical and autopsy-based reports that describe a broad range of SCV2-associated neurological conditions, it is unclear what fraction of these have been due to direct CNS invasion versus indirect effects caused by systemic reactions to critical illness. Still critically lacking is a comprehensive tissue-based survey of the CNS presence and specific neuropathology of SCV2 in humans. We conducted an extensive neuroanatomical survey of RT-PCR-detected SCV2 in 16 brain regions from 20 subjects who died of COVID-19 disease. Targeted areas were those with cranial nerve nuclei, including the olfactory bulb, medullary dorsal motor nucleus of the vagus nerve and the pontine trigeminal nerve nuclei, as well as areas possibly exposed to hematogenous entry, including the choroid plexus, leptomeninges, median eminence of the hypothalamus and area postrema of the medulla. Subjects ranged in age from 38 to 97 (mean 77) with 9 females and 11 males. Most subjects had typical age-related neuropathological findings. Two subjects had severe neuropathology, one with a large acute cerebral infarction and one with hemorrhagic encephalitis, that was unequivocally related to their COVID-19 disease while most of the 18 other subjects had non-specific histopathology including focal β-amyloid precursor protein white matter immunoreactivity and sparse perivascular mononuclear cell cuffing. Four subjects (20%) had SCV2 RNA in one or more brain regions including the olfactory bulb, amygdala, entorhinal area, temporal and frontal neocortex, dorsal medulla and leptomeninges. The subject with encephalitis was SCV2-positive in a histopathologically-affected area, the entorhinal cortex, while the subject with the large acute cerebral infarct was SCV2-negative in all brain regions. Like other human coronaviruses, SCV2 can inflict acute neuropathology in susceptible patients. Much remains to be understood, including what viral and host factors influence SCV2 brain invasion and whether it is cleared from the brain subsequent to the acute illness.

scholarly journals The Neural Pathway of Reflex Regulation of Electroacupuncture at Orofacial Acupoints on Gastric Functions in Rats

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Jianhua Liu ◽  
Wenbin Fu ◽  
Wei Yi ◽  
Zhenhua Xu ◽  
Nenggui Xu
Keyword(s):  
Myoelectric Activity ◽  
Motor Nucleus ◽  
Dorsal Vagal Complex ◽  
Solitary Tract ◽  
Neural Pathway ◽  
Excitatory Effect ◽  
Reflex Regulation ◽  
Gastric Myoelectric Activity ◽  
Dorsal Motor Nucleus ◽  
Spike Bursts

Acupuncture has a reflex regulation in gastrointestinal functions, which is characterized with segment. In the present study, the neural pathway of electroacupuncture (EA) at orofacial acupoints (ST2) on gastric myoelectric activity (GMA) in rats was investigated. The results indicated that EA at ST2 facilitated spike bursts of GMA, which is similar to EA at limbs and opposite to EA at abdomen. The excitatory effect was abolished by the transaction of infraorbital nerves, dorsal vagal complex lesion, and vagotomy, respectively. In addition, microinjection of L-glutamate into the nucleus of the solitary tract (NTS) attenuated the excitatory effect. All these data suggest that the dorsal vagal complex is involved in the reflex regulation of EA at orofacial acupoints on gastric functions and NTS-dorsal motor nucleus of the vagus (DMV) inhibitory connections may be essential for it.

Glutamatergic plasticity within neurocircuits of the dorsal vagal complex and the regulation of gastric functions

2021 ◽  
Author(s):  
Courtney Clyburn ◽  
Kirsteen N Browning
Keyword(s):  
Food Intake ◽  
Energy Homeostasis ◽  
Intestinal Secretion ◽  
Motor Nucleus ◽  
Glutamatergic Transmission ◽  
Gi Tract ◽  
Dorsal Motor Nucleus ◽  
Efferent Neurons ◽  
Rapid Transmission

The meticulous regulation of the gastrointestinal (GI) tract is required for the co-ordination of gastric motility and emptying, intestinal secretion, absorption, and transit as well as for the overarching management of food intake and energy homeostasis. Disruption of GI functions is associated with the development of severe GI disorders as well as the alteration of food intake and caloric balance. Functional GI disorders as well as the dysregulation of energy balance and food intake are frequently associated with, or result from, alterations in the central regulation of GI control. The faithful and rapid transmission of information from the stomach and upper GI tract to second order neurons of the nucleus of the tractus solitarius (NTS) relies on the delicate modulation of excitatory glutamatergic transmission, as does the relay of integrated signals from the NTS to parasympathetic efferent neurons of the dorsal motor nucleus of the vagus (DMV). Many studies have focused on understanding the physiological and pathophysiological modulation of these glutamatergic synapses, although their role in the control and regulation of GI functions has lagged behind that of cardiovascular and respiratory functions. The purpose of this review is to examine the current literature exploring the role of glutamatergic transmission in the DVC in the regulation of Gl functions.

Prior vagotomy blocks VMH obesity in pair-fed rats

1981 ◽  
Vol 240 (5) ◽  
pp. E573-E583 ◽  
Author(s):  
J. E. Cox ◽  
T. L. Powley
Keyword(s):  
Food Intake ◽  
Cell Loss ◽  
Ventromedial Hypothalamus ◽  
Motor Nucleus ◽  
Previous Suggestion ◽  
Hypothalamic Obesity ◽  
Dorsal Motor Nucleus ◽  
Gastric Contents ◽  
Feeding Regimen ◽  
Protein Output

Previously vagotomized, ventromedial hypothalamus (VMH)-lesioned rats and sham-lesioned controls were maintained on an intragastric pair-feeding regimen in which nonvagotomized VMH rats deposit excessive fat. Hypothalamic lesions were produced after 6 days of adaptation to pair feeding, and the experiment continued for 30 days postlesion. Extent of vagotomy was determined with a multiple-regression procedure with cell loss in the dorsal motor nucleus of the vagus, fasting gastric contents, and basal pancreatic protein output as predictor variables. The correlation was 0.95 between this set of indexes and the adequacy of a vagotomy for preventing hypothalamic obesity. Thus, radical vagotomies precluded the typical accumulation of significantly increased levels of carcass fat in lesioned animals (16.3 vs. 14.0% for controls). VMH rats with less extensive transections accumulated substantially more fat (25.9%). This outcome suggests that vagotomy produces a specific blockade of lesion-produced disturbances in metabolism leading to obesity. It fails to support a previous suggestion that vagal section blocks VMH obesity merely as a nonspecific surgical restriction of food intake because vagotomy was effective even though its effects on food intake could not operate.

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