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.

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 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.

scholarly journals Single-cell mapping of GLP-1 and GIP receptor expression in the dorsal vagal complex

Diabetes ◽  
2021 ◽  
pp. dbi210003
Author(s):  
Mette Q. Ludwig ◽  
Petar V. Todorov ◽  
Kristoffer L. Egerod ◽  
David P. Olson ◽  
Tune H. Pers
Keyword(s):  
Single Cell ◽  
Receptor Expression ◽  
Dorsal Vagal Complex ◽  
Cell Mapping ◽  
Gip Receptor

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.

Galanin Inhibits Gut-Related Vagal Neurons in Rats

2004 ◽  
Vol 91 (5) ◽  
pp. 2330-2343 ◽  
Author(s):  
Zhenjun Tan ◽  
Ronald Fogel ◽  
Chunhui Jiang ◽  
Xueguo Zhang
Keyword(s):  
Potassium Channel ◽  
Reversal Potential ◽  
Outward Current ◽  
Motor Nucleus ◽  
Dorsal Vagal Complex ◽  
Solitary Tract ◽  
Membrane Hyperpolarization ◽  
Dorsal Motor Nucleus

Galanin plays an important role in the regulation of food intake, energy balance, and body weight. Many galanin-positive fibers as well as galanin-positive neurons were seen in the dorsal vagal complex, suggesting that galanin produces its effects by actions involving vagal neurons. In the present experiment, we used tract-tracing and neurophysiological techniques to evaluate the origin of the galaninergic fibers and the effect of galanin on neurons in the dorsal vagal complex. Our results reveal that the nucleus of the solitary tract is the major source of the galanin terminals in the dorsal vagal complex. In vivo experiments demonstrated that galanin inhibited the majority of gut-related neurons in the dorsal motor nucleus of the vagus. In vitro experiments demonstrated that galanin inhibited the majority of stomach-projecting neurons in the dorsal motor nucleus of the vagus by suppressing spontaneous activity and/or producing a fully reversible dose-dependent membrane hyperpolarization and outward current. The galanin-induced hyperpolarization and outward current persisted after synaptic input was blocked, suggesting that galanin acts directly on receptors of neurons in the dorsal motor nucleus of the vagus. The reversal potential induced by galanin was close to the potassium ion potentials of the Nernst equation and was prevented by the potassium channel blocker tetraethylammonium, indicating that the inhibitory effect of galanin was mediated by a potassium channel. These results indicate that the dorsal motor nucleus of the vagus is inhibited by galanin derived predominantly from neurons in the nucleus of the solitary tract projecting to the dorsal motor nucleus of the vagus nerve. Galanin is one of the neurotransmitters involved in the vago-vagal reflex.

Studies of the Central Neural Pathways to the Stomach and Zusanli (ST36)

2001 ◽  
Vol 29 (02) ◽  
pp. 211-220 ◽  
Author(s):  
Chang Hyun Lee ◽  
Han Sol Jung ◽  
Tae Young Lee ◽  
Sang Ryoung Lee ◽  
Sang Won Yuk ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Vagus Nerve ◽  
Nucleus Tractus Solitarius ◽  
Area Postrema ◽  
Reticular Nucleus ◽  
Hypothalamic Nucleus ◽  
Cell Group ◽  
Motor Nucleus ◽  
Amygdaloid Nucleus ◽  
Dorsal Motor Nucleus

The purpose of this morphological study was to investigate the relation between the meridian, meridian points and viscera using neuroanatomical tracers. The common locations of the spinal cord and brain projecting to the stomach and Zusanli were observed following injection of CTB (cholera toxin B subunit) and pseudorabies viruses (PRV-Ba, Bartha strain and PRV-Ba-Gal, galactosidase insertion) into the stomach and Zusanli (ST36). After 4–5 days of survival following injection into twelve rats, they were perfused, and their spinal cords and brains were frozen sectioned (30 μm). These sections were stained by X-gal histochemical, CTB and PRV-Bia immunohistochemical staining methods, and examined with the light microscope. The results were as follows: Commonly labeled medulla oblongata regions were dorsal motor nucleus of vagus nerve (DMV), nucleus tractus solitarius (NTS) and area postrema (AP) following injection of CTB and PRV-Ba-Gal into stomach and Zusanli, respectively. In the spinal cord, commonly labeled neurons were found in thoracic, lumbar and sacral spinal segments. Densely labeled areas were found in lamina IV, V, VII (intermediolateral nucleus) and X of the spinal cord. In the brain, commonly labeled neurons were found in the A1 noradrenalin cells/C1 adrenalin cells/caudoventrolateral reticular nucleus, dorsal motor nucleus of vagus nerve, nucleus tractus solitarius, area postrema, raphe obscurus nucleus, raphe pallidus nucleus, raphe magnus nucleus, gigantocellular nucleus, locus coeruleus, parabrachial nucleus, Kolliker-Fuse nucleus, A5 cell group, central gray matter, paraventricular hypothalamic nucleus, lateral hypothalamic nucleus, retrochiasmatic hypothalamic nucleus, bed nucleus of stria terminals and amygdaloid nucleus. Thus central autonomic center project both to the stomach and Zusanli. These morphological results suggest that there is a commonality of CNS cell groups in brain controlling stomach (viscera) and Zusanli (limb).

Cardiovascular responses to microinjection of ANF into dorsal medulla of rats

1988 ◽  
Vol 255 (1) ◽  
pp. R182-R187 ◽  
Author(s):  
D. J. McKitrick ◽  
F. R. Calaresu
Keyword(s):  
Area Postrema ◽  
Cardiovascular Responses ◽  
Significant Decline ◽  
Medial Longitudinal Fasciculus ◽  
Hypoglossal Nucleus ◽  
Cardiovascular Reflexes ◽  
Motor Nucleus ◽  
Cuneate Nucleus ◽  
Dorsal Motor Nucleus ◽  
Dorsal Medulla

Atrial natriuretic factor (ANF) has been suggested as a putative neurotransmitter in central pathways involved in the control of the cardiovascular system. To investigate this possibility, 50 nl of 10(-7) M ANF were microinjected into discrete sites in the nucleus of the tractus solitarius (NTS) where baro- and chemoreceptor afferents terminate. Injections into 36 of a total of 66 sites in the NTS of paralyzed artificially ventilated Wistar rats under urethan anesthesia were found to produce a significant decline in heart rate [HR; -9.2 +/- 2.9 (SE) beats/min, P less than 0.05] and mean arterial pressure [MAP; -11.1 +/- 1.2 (SE) mmHg, P less than 0.01]. Similar responses were also present in anesthetized animals breathing spontaneously. Microinjection of an inactive peptide analogue or of saline did not produce cardiovascular changes. It was also found that ANF injection into the cuneate nucleus (20 of 38 sites) and the spinal trigeminal complex (28 of 42 sites) produced a decrease in MAP and HR that were of the same magnitude as those seen in the NTS. Injections of ANF into the medial longitudinal fasciculus (n = 22), hypoglossal nucleus (n = 9), area postrema (n = 16), and dorsal motor nucleus of the vagus (n = 11) did not change HR or MAP. These results suggest that ANF may serve as a neurotransmitter involved in cardiovascular reflexes mediated by specific nuclei in the dorsal medulla.

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